Catalytic functionalization of tertiary alcohols to fully substituted carbon centres.

Volume 12 Number 32 28 August 2014 Pages 6017–6280

Organic & Biomolecular Chemistry www.rsc.org/obc

ISSN 1477-0520

REVIEW ARTICLE Jian Zhou et al. Catalytic functionalization of tertiary alcohols to fully substituted carbon centres

Organic & Biomolecular Chemistry View Article Online

Published on 21 May 2014. Downloaded by The University of Melbourne Libraries on 14/10/2014 06:17:44.

REVIEW

Cite this: Org. Biomol. Chem., 2014, 12, 6033

View Journal | View Issue

Catalytic functionalization of tertiary alcohols to fully substituted carbon centres Long Chen, Xiao-Ping Yin, Cui-Hong Wang and Jian Zhou* The catalytic nucleophilic substitution of tertiary alcohols using carbon or heteroatom based nucleophiles is a versatile methodology for the efficient, diverse and atom economical construction of fully substituted

Received 4th April 2014, Accepted 21st May 2014

carbon centres, including both quaternary carbons and heteroatom substituted tetrasubstituted carbons,

DOI: 10.1039/c4ob00718b

which only produces water as the by-product. This review summarizes the recent progress in this field, including the catalytic asymmetric studies and their application in the natural product synthesis, briefly

www.rsc.org/obc

discusses the reaction mechanism and challenges, and outlines synthetic opportunities that are still open.

1.

Introduction

The efficient construction of fully substituted carbon centres is a very important task in organic synthesis,1 owing to their wide occurrence in natural products, drugs and value-added products such as 3,3-disubstituted oxindoles2 or benzofuranones,3 tertiary alcohols,4 α-tertiary amines,4 Cα-tetrasubstituted α-amino acids5 and tetrasubstituted carbons featuring an α-fluorine, sulfur or other heteroatom-based substituents.6 In particular, how to efficiently construct quaternary carbon atoms that bonded to four carbon substituents is generally regarded as very difficult in organic synthesis,7 due to unfavourable steric hindrance and relatively low reactivity of precursors, and the corresponding catalytic asymmetric con-

Shanghai Key Laboratory of Green Chemistry and Chemical Processes, Department of Chemistry, East China Normal University, 3663 N. Zhongshan Road, Shanghai 200062, P. R. China. E-mail: [email protected]; Fax: +86 21-6223-4560; Tel: +86 21-6223-4560

struction of all-carbon quaternary stereogenic centres represents a formidable challenge in synthetic chemistry.8 Therefore, the development of general, efficient and atomeconomical strategies to furnish fully substituted carbons is highly desirable and constitutes a highly active research field. In this context, the acid catalyzed nucleophilic substitution of tertiary alcohols, mainly through a dehydrative path, emerges as a versatile strategy to construct various types of fully substituted carbons, as both carbon and heteroatom based nucleophiles are viable for the reaction development. Generally, a carbocationic intermediate ion-paired with a counteranion is involved in the reaction (Scheme 1). As can be reasonably deduced, the easier the formation of the carbocationic intermediates, the stronger the nucleophiles, and the smoother the desired reactions. Therefore, the α-electronreleasing groups of tertiary alcohols facilitate the reaction, while the electron-withdrawing substituents retard the reaction. Noticeably, if a chiral catalyst is used as the catalyst, together with the formation of a compact ion-pair, it is

Long Chen was born in 1988 in Dazhou, Sichuan province of China. He studied chemistry at the Sichuan Normal University, where he obtained his bachelor degree in 2010. He joined Prof. Jian Zhou’s group in the same year as a PhD student at East China Normal University. His research interests focus on the study of highly atom-economical reactions. Long Chen

This journal is © The Royal Society of Chemistry 2014

Xiao-Ping Yin was born in 1989 in Ziyang, Sichuan province of China. He studied material chemistry at the Sichuan Normal University, where he obtained his bachelor degree in 2013. He is now doing his masters research in East China Normal University, under the guidance of Professor Jian Zhou.

Xiao-Ping Yin

Org. Biomol. Chem., 2014, 12, 6033–6048 | 6033

View Article Online


Review

Scheme 1

Organic & Biomolecular Chemistry

Catalytic functionalization of tertiary alcohols.

possible to develop the corresponding catalytic asymmetric variants, which represents one of the most exciting latest achievements in this area. In addition, this strategy has two important advantages: (i) high atom-economy,9 because only water is produced as the by-product; and (ii) excellent diversity, as differently substituted tertiary alcohols could be readily coupled with various types of nucleophiles, allowing facile construction of libraries of compounds featuring a fully substituted carbon centre in sufficient structural diversity, which is very attractive in medicinal research. The investigation of dehydrative functionalization of tertiary alcohols has a long and continuing history, but traditional studies were based on the use of stoichiometric amounts of Brønsted acid or Lewis acid catalysts. To highlight the importance of this methodology in the natural product synthesis, two notable early examples using stoichiometric amounts of acid catalysts were given in Scheme 2. In the total synthesis of diazonamide A developed by Nicolaou et al. in 2002, the key step was the Friedel–Crafts arylation of 3-hydroxy-2-oxindole 1a using the amino acid derivative 2, which was achieved in the presence of 4.0 equiv. of p-TsOH, albeit in only 47% yield (eqn (1)).10 This protocol was soon adopted by Halperin for the building up of a library of 3,3-diaryloxindoles, and m′-tert-butyl and o-hydroxy substituted diphenyloxindole

Cui-Hong Wang obtained his PhD degree in 2006 from Nanjing University, and she spent two years working as a postdoctoral fellow with Professor Yin-Long Guo in Shanghai Mass Spectrometry Center, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences. She joined the Shanghai Key Laboratory of Green Chemistry and Chemical Processes at East China Normal Cui-Hong Wang University as an associate Professor from October of 2008. Her current research interests include the exploration of the mechanism of organic reactions with the help of isotope labeling, and the synthesis and studies of functional materials of mass spectrometry matrices in the MALDI mass spectrometry field.

6034 | Org. Biomol. Chem., 2014, 12, 6033–6048

Scheme 2

Selected synthetic application.

was identified as a lead compound for Ca2+-depletionmediated inhibition of translation.11 Later in 2010, Nicolaou and Chen further utilized 3.0 equiv. of Lewis acid BF3·Et2O to promote an intramolecular Friedel–Crafts reaction of α-hydroxyester 4a, which was the key step for the construction

Jian Zhou obtained his PhD degree in 2004 from the Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, under the guidance of Prof. Yong Tang. After spending one year working as a postdoctoral fellow with Professor Shū Kobayashi at the University of Tokyo, three years with Professor Benjamin List at MaxPlanck-Institut für Kohlenforschung, he joined the ShangJian Zhou hai Key Laboratory of Green Chemistry and Chemical Processes at East China Normal University as a Professor from the end of 2008. His current research interests include the development of new chiral catalysts and new asymmetric reactions. He has received the “Thieme Chemistry Journal Award 2011”. He is now the member of the Advisory Board of Organic & Biomolecular Chemistry.


View Article Online



of the desired quaternary benzolactone backbone 5 for the total synthesis of hopeahainol A (eqn (2)).12 In both cases, acid catalysts were used in high loading, possibly to compensate the destabilizing effect of the electron-withdrawing amide or ester group on the corresponding carbocation intermediate. Gratifyingly, in the last decade, much progress has been made in the utilization of catalytic amounts of acids to enable the direct functionalization of tertiary alcohols. Not only the scope of tertiary alcohols is greatly expanded from tertiary alcohols with electron-releasing aryl or alkyl groups to those with a strong electron-withdrawing ketone or ester group at the α position, but also the corresponding catalytic asymmetric studies have been realized and applied to the total synthesis of natural products. Therefore, it is necessary to make a comprehensive summarization of the latest achievements, and discuss the challenges, opportunities and further developments in this field. Although Klumpp most recently made an excellent review on contemporary carbocation chemistry,13 it just mentioned some examples of catalytic functionalization of tertiary alcohols, not focused on the in-depth summarization of the achievements and the actual state of this research, and even the catalytic asymmetric versions were not included. Therefore, here we sum up the advances in the catalytic functionalization of tertiary alcohols for the facile synthesis of fully substituted carbons. The scope, limitations, possible mechanism and synthetic tasks are also discussed. This review article is divided into two parts: (i) racemic reactions and (ii) catalytic asymmetric versions, for the convenience of readers to have an overview of this topic.

2. Racemic reaction 2.1.

C–C bond formation reactions

The catalytic coupling of tertiary alcohols with carbon based nucleophiles allows the construction of quaternary carbon centres. Electron-rich aromatic compounds such as indoles, furans, thiophenes, pyrroles and substituted phenols are the most popular nucleophiles for the direct functionalization of tertiary alcohols via Friedel–Crafts reaction.14 Such an arylation of tertiary α-hydroxy ketones and esters could be viewed as an atom-economical strategy for the α-arylation of ketones and esters, complementary to transition metal catalyzed protocols. In the following, the known examples since 2005 were sorted by the types of tertiary alcohols. Tertiary alcohols with all the three α groups that can stabilize the carbocationic intermediates, including aryl, aliphatic, alkene and alkynyl groups, prove to be highly efficient for reaction design as expected, with a number of intra- or intermolecular arylation reactions being developed. In 2006, Rueping et al. reported that only 1 mol% of Bi(OTf )3, a water-tolerable Lewis acid, catalyzed the intramolecular Friedel–Crafts reaction of biphenyl derivatives 6 well, to furnish substituted fluorenes 7 that were valuable scaffolds for blue light emitting polymers (Scheme 3).15 Previously, such an intramolecular arylation reaction entailed harsh conditions such as refluxing in


Review

Scheme 3

Bi(OTf )3 catalyzed intramolecular reaction of 6.

sulfuric acid, which was in sharp contrast to the high efficiency and mild reaction conditions achieved by Bi(OTf )3. Usually, halogenated solvents, toluene, CH3CN and CH3NO2, are widely used reaction media, but sometimes water could serve as the medium as well. For example, Shirakawa and Kobayashi reported in 2007 that dodecylbenzenesulfonic acid (DBSA), a surfactant-type Brønsted acid, efficiently catalyzed the dehydrative nucleophilic substitution of benzyl alcohols with a variety of carbon- and heteroatom-based nucleophiles.16 In this report, two tertiary alcohols 8a and 8b were found to be able to react with N-methylindole to yield 3-substituted indoles bearing a quaternary center in excellent yields (Scheme 4).Very interestingly, alcohol 8b, apt to undergo elimination reaction to give α-methylstyrene in the presence of an acid catalyst, afforded the desired product 10b in 95% yield. Also in 2007, the same C3-selective alkylation of N-methyl indole 9a using alcohol 8b was reported to work well in the presence of 10 mol% of FeCl3 by Jana et al. (Scheme 5).17 In 2010, McCubbin et al. found that commercially available pentafluorophenylboronic acid is a good catalyst for the Friedel–Crafts arylation of tertiary alcohols 8 using five-membered electron-rich heterocycles such as indole, pyrrole and 2-methylfuran, giving tetrasubstituted methanes 11 in moderate to good yields (Scheme 6).18 The authors proposed that the complexation of boronic acid to the alcohol 8 led to the formation of the intermediate I, which enhanced the leaving ability of the hydroxyl group to produce a resonance-stabilized carbocation, followed by the attack of the aromatics to afford the product. The arylboronic acid was regenerated with the help of molecular sieves to remove water from arylborate. Owing to the great interest in C3 alkylated indole derivatives for medicinal research, the Friedel–Crafts arylation of

Scheme 4

DBSA catalyzed indole arylation.

Scheme 5

FeCl3 catalyzed indole arylation.

Org. Biomol. Chem., 2014, 12, 6033–6048 | 6035

View Article Online


Review

Scheme 6


C6F5B(OH)2 catalyzed Friedel–Crafts arylation. Scheme 8

indoles using various alcohols was then examined. For example, in 2008, Sanz et al. reported the use of only 5 mol% of p-TsOH to catalyze the C3-propargylation of 2-unsubstituted indoles 9 using tertiary propargylic alcohols 12, giving C3-propargylic indoles 13 with a quaternary center adjacent to its C3 position in moderate to excellent yields (Scheme 7).19a Tertiary benzylic alcohols and vinyl-substituted alkynols 14 are also workable in this reaction. The propargylation reaction could not occur in the absence of p-TsOH. On the other hand, even without the participation of nucleophilic indoles but in the presence of p-TsOH, the formation of the enyne derivative was observed, indicating the high tendency of tertiary propargylic alcohols to undergo acid catalyzed elimination. Further studies showed that this protocol has a broad substrate scope for the synthesis of 3-propargylic indoles with quaternary carbon centers.19b Tertiary propargylic alcohols, without the activation of an additional aryl substituted at the α-position, are known to be difficult to participate in the intermolecular Friedel–Crafts alkylations. In 2010, Niggemann et al. reported that the use of a catalyst system consisting of 5 mol% Ca(NTf2)2 and 5 mol% Bu4NPF6 enabled the arylation reaction of propargylic alcohols such as 12a or benzylic alcohol 8a using 1,3-dimethoxybenzene 16 to work well at room temperature to provide the desired products in good to excellent yields (Scheme 8).20 No reaction occurred in the absence of Bu4NPF6, demonstrating the possible formation of a more reactive CaNTf2·PF6 species. Apart from 1,3-dimethoxybenzene, 2-methylthiophene, mesitylene, phenol and 1-bromo-2,4-dimethoxybenzene were also viable substrates to work with alcohol 12a under this condition. This protocol avoided the use of strong acids and special precautions for exclusion of moisture, very attractive for the synthesis of quaternary carbons featuring an alkynyl group and an aryl group at the α position.

Scheme 7

p-TsOH catalyzed C3-propargylation of indoles.

6036 | Org. Biomol. Chem., 2014, 12, 6033–6048

Calcium-catalyzed arylation of tertiary alcohols.

In 2012, Bezuidenhoudt et al. reported that Al(OTf )3 was a reusable Lewis acid for the Friedel–Crafts alkylation of indoles with tertiary propargylic alcohols (Scheme 9).21 Under the catalysis of 2 mol% of Al(OTf )3, a variety of propargylic alcohols, activated by an aryl group at the α-position of the hydroxy group, could react with indoles to give the desired product in up to 94% yield. It was reported that Al(OTf )3 could be recycled and reused three times without the loss of reactivity. Intramolecular Friedel–Crafts arylation of tertiary alcohols allowed the synthesis of disubstituted tetrahydronaphthalenes, (thio)chromans and tetrahydroisoquinolines, interesting for medicinal research. In 2013, Bunce et al. reported that Bi(OTf )3 was more efficient than other acid catalysts such as AlCl3, FeCl3·6H2O, p-TsOH, and CH3SO2H in this reaction, to suppress the fragmentation of substrates and side reactions (Scheme 10).22 With the optimized protocol, a variety of carbocyclic and heterocyclic compounds could be prepared, in the presence of 10–20 mol% of Bi(OTf )3. Noticeably, alkenes formed from the competitive dehydration of the starting materials could be further transformed to the desired cyclic products. In addition to electron-rich aromatics, other carbon based nucleophiles such as TMSCN and allyltrimethylsilanes are also viable for the functionalization of tertiary alcohols. In 2008, Ding et al. reported that InBr3 or InCl3 could efficiently catalyze the cyanation of sterically demanding tertiary alcohols using TMSCN for the synthesis of α-aryl nitriles, valuable building blocks, in good to excellent yields (Scheme 11).23 The easily available starting materials and catalysts made this process very useful for the synthesis of precursors of cicloprofen and indoprofen. In 2011, the Niggemann group extended the scope of the calcium catalyst for the nucleophilic substitution of tertiary

Scheme 9

Al(OTf )3 catalyzed indole alkylation.


View Article Online



Review

3-hydroxy-3-indolyindolin-2-ones 1 with indoles or pyrroles to afford the corresponding adducts 3 in excellent yields under ultrasound irradiation. This constituted an efficient route for the synthesis of symmetrical and unsymmetrical 3,3-di(indolyl)indolin-2-one (Scheme 13).25 The key to the success of this protocol might result from the high reactivity of 3-hydroxy-3-indolyindolin-2-ones, as the C3 indolyl group might stabilize the intermediate positive charge via the formation of an iminium intermediate I. In 2007, Padwa et al. examined the reaction of 3-methyl-3hydroxyoxindole 1b with a variety of π-nucleophiles, and found that 20 mol% p-TsOH catalyzed the reaction at reflux in CH2Cl2 to give the desired product in moderate to high yields, albeit with high usage of nucleophiles (Scheme 14).26 They also proposed quasi-antiaromatic 2H-indol-2-one (I) as the reactive intermediate. The synthesis of spiro-substituted oxidole 3f from 1c via an intramolecular fashion in the presence of 3.0 equiv. of BF3·Et2O was also reported. Scheme 10

Bi(OTf )3 catalyzed intramolecular cyclization.

Scheme 11

In-catalyzed cyanation of tertiary alcohols.

propargylic alcohols using allyltrimethylsilane, providing the desired allylic substituted products 21 in moderate yields (Scheme 12).24 In parallel to the efforts on direct functionalization of tertiary alcohols with three α substituents that could stabilize the cationic intermediates, much attention has been paid to the tertiary alcohols with at least one electron-withdrawing group at the α position of the alcohol. In this context, 3-substituted 3-hydroxyoxindoles 1 represent a class of tertiary alcohols of current interest, as the resulting 3,3-disubstituted oxindoles are privileged scaffolds in medicinal research. While Nicolaou et al. used 4.0 equiv. of p-TsOH to promote the arylation reaction of 3-hydroxyoxindoles in the total synthesis of diazonamide A, much progress has been made in the development of catalytic protocols since then. In 2006, Wang and Ji revealed that ceric ammonium nitrate (CAN) catalyzed the reaction of

Scheme 12

Ca-catalyzed allylation of propargylic alcohols.


Scheme 13

CAN catalyzed indole alkylation.

Scheme 14

Catalytic functionalization of 3-hydroxyoxindoles.

Org. Biomol. Chem., 2014, 12, 6033–6048 | 6037

View Article Online


Review


With our continuous efforts in the development of efficient methods for the synthesis of various types of 3,3-disubstituted oxindoles,27 we reported in 2011 that Hg(ClO4)2·3H2O was a highly efficient catalyst for the Friedel–Crafts arylation of 3-aryl, 3-methyl and 3-allyl 3-hydroxyoxindoles 1 with a broad scope of (hetero)aromatic compounds, including (halogenated) indoles, 2-methyl substituted furan or thiophene, p-tert-butylphenol 1,3-dimethoxybenzene, N-methylpyrrole and N-acetylindoline. With only 5 mol% of cheap Hg(ClO4)2·3H2O and only 1.2 equiv. of nucleophiles, a number of unsymmetric 3,3diaryloxindoles or 3-alkyl-3-aryloxidoles were prepared with sufficient structural diversity (Scheme 15).28 Under these conditions, the reaction of 3-hydroxyoxindole 1d (89% ee) and N-methyl indole gave the racemic product, suggesting the formation of a planar carbocationic intermediate. As Hg(ClO4)2·3H2O proved to be more powerful than other widely used Lewis acids or Brønsted acids in this reaction, the mechanistic studies were undertaken with UV/Vis titration experiments and NMR studies. It was proposed that the high activity of Hg(ClO4)2·3H2O resulted from the unprecedented

dual activation effects of aromatic mercuration of the electronrich arene: the production of a strong acid (HClO4) to facilitate the dehydration of 3-substituted-3-hydroxyoxindoles to form a carbocation intermediate to react with the simultaneously formed reactive nucleophilic ArHgClO4. Later in 2012, the Bisai group examined the potency of In(OTf )3, Cu(OTf )2 and Bi(OTf )3 in the arylation of 3-hydroxyoxindoles using phenol derivatives 22. It was found that 10–40 mol% metal triflates were needed to allow the reaction of 3-alkyl or 3-acetenyl 3-hydroxyoxindoles with phenols to give the corresponding 3,3-disubstituted oxindoles in moderate to good yields (Scheme 16).29 Compared with Zhou’s protocol using only 5 mol% Hg(ClO4)2·3H2O, the indium, copper and bismuth triflate catalyzed versions suffered from high catalyst loading, and it remained unknown whether these metal triflates could catalyze the reaction of 3-aryl 3-hydroxyoxindoles with phenols. This result further suggested that although toxic, the mercury catalyst has some unique properties worthwhile to explore. The authors also demonstrated the utility of the product 3p by a conversion to the tetracyclic core 23 of azonaine via an intramolecular oxidative coupling. In 2013, Zhu reported a one-pot protocol for the synthesis of 3,3-disubstituted oxindoles 3 from 3-hydroxyoxindoles 1 via 10 mol% DBU catalyzed conversion of 3-hydroxyoxindoles to trichloroacetimidates I and subsequent diphenylphosphoric acid catalyzed substitution reaction using various carbon or heteroatom based nucleophiles (Scheme 17).30 The fact that the reaction of enantioenriched trichloroacetimidate with methanol under standard conditions resulted in racemization of the product, together with the DFT calculations, the authors proposed that the reaction proceeded through the 1-alkyl-2oxo-2H-indol-1-ium intermediate II. Recently, Klumpp et al. reported that in the presence of 10 equiv. of HOTf, pyridyl-substituted 3-hydroxy-2-oxyindoles 1 reacted with substituted benzenes to give quaternary oxindoles 3 in moderate to good yields (Scheme 18).31 Furthermore, the regioselectivity was excellent when toluene, bromobenzene and ethyl salicylate were used. The authors proposed that the reaction began with ionization of hydroxyoxindole 1 to pyridyl-

Scheme 15

Scheme 16

Hg-catalyzed arylation of 3-hydroxyoxindoles.

6038 | Org. Biomol. Chem., 2014, 12, 6033–6048

Friedel–Crafts reaction of 3-hydroxy-2-indole 1b.


View Article Online



Review

Scheme 20

Scheme 17

One-pot Brønsted base and Brønsted acid catalysis.

Scheme 18

CF3SO3H promoted Friedel–Crafts arylation.

oxonium dication I, followed by a dehydration to give the superelectrophilic carbocation II which underwent Friedel– Crafts reaction with arenes to give the corresponding products 3. The key to this reaction is the use of superacidic conditions to form dicationic, superelectrophiles. Carboline derivatives are important class of indole derivatives for their versatile biological activities. In 2013, Wang and Ji developed a simple and efficient protocol for the construction of α-carboline derivatives from 3-hydroxy-3-(1H-indo-3-yl)-1-methylindolin-2-one 1d with enaminones via an iodine-catalyzed cascade formal [3 + 3] cycloaddition reaction (Scheme 19).32 In 2013, Bisai further reported a Sn(OTf )2 catalyzed coupling reaction of 3-hydroxyoxindoles using allyltrimethylsilane,

Scheme 19

[3 + 3] cycloaddition reaction to α-carbolines.


Sn(OTf )2 promoted functionalization reaction.

phenylacetylene and styrenes to give diverse quaternary oxindoles with different functionalities at the C3 position in good yields (Scheme 20).33 When phenylacetylene was used as the nucleophile, no traces of the phenylacetylene addition product was observed, but the adduct 3u was prepared in 89% yield, which was also obtained using acetophenone as the nucleophile. Encouraged by HClO4 catalyzed functionalization of tertiary alcohols with electron-withdrawing groups developed by Zhou’s group,34–36 the authors also found that HClO4 could catalyze the substitution reaction using allyltrimethylsilane efficiently. Apart from 3-substituted hydroxyoxindoles, α-hydroxy esters or ketones were also tried in the acid-catalyzed arylation reaction. In 2011, Wu, Wang and Chen identified Hf(OTf )4 as a powerful catalyst for indole alkylation of chromene hemiacetals 26, the direct derivatization of which was a considerable synthetic challenge due to the existing multifunctional system (Scheme 21).37 It was found that only 0.1 mol% of Hf(OTf )4 promoted the reaction efficiently to afford the desired adduct 27 in up to 99% yield within 0.5 h. While the use of stoichiometric amounts of some metal salts such as CuCl2, ZnCl2, and TiCl3 could catalyze the reaction well, lowering the catalyst loading to 10 mol% dramatically diminished the yield. In addition, Hf(OTf )4 also proved to be more efficient in this

Scheme 21

Indole alkylation of the chromene hemiacetal 26.

Org. Biomol. Chem., 2014, 12, 6033–6048 | 6039

View Article Online


Review


reaction than other widely used Lewis acids in Friedel–Crafts reaction, such as FeCl3, In(OTf )3, Yb(OTf )3 and Sc(OTf )3. The use of only 0.1 mol% Hf(OTf)4 allowed chromene hemiacetals 26 to be coupled with indoles, furans and sterically hindered anilines smoothly to afford the corresponding products with high selectivity and 73–99% yield. The high efficiency of the protocol might be related to the stabilization of the cationic intermediate I by the oxygen at the α position, which alleviated the destabilizing effect of the electron-withdrawing ester group. Even tertiary α-hydroxy esters or ketones, without an α-heteroatom to stabilize the cationic intermediate, are viable substrates for the catalytic dehydrative substitution reaction, in the presence of a strong acid catalyst. In 2012, as an extension of our research on arylation of 3-hydroxyindoles,28 we examined the arylation of tertiary α-hydroxy esters using phenols, and found that in the presence of 10 mol% of HClO4, a tandem Friedel–Crafts/lactonization reaction occurred, affording 3,3-diaryl or 3-alkyl-3-aryl benzofuranones 28 bearing a C3 quaternary centre in good to high yields (Scheme 22).35 The reaction path was also supported by NMR analysis. Under the reported conditions, a variety of tertiary α-hydroxyesters 4 readily reacted with differently substituted phenols 22 to give the desired products with high structural diversity. A good merit of this protocol was that the bromo substituent, either on the hydroxyoxindole or on the nucleophilic phenols, could be tolerated, which provided a very useful syn-

thetic handle for further transformation. For example, the product 28a could be converted to a variety of polycyclic compounds 31, 32 and 33 using suitable conditions. We further extended this protocol to the arylation of α-hydroxyesters 4 using aromatic compounds other than phenols, or the arylation of α-hydroxyketones with various electron-rich aromatics, which readily afforded the corresponding α-quaternary esters or ketones in moderate to high yields (Scheme 23).36 Indoles, furan, thiophene and anisoles could all participate in the reactions. The loading of the HClO4 catalyst was dependent on the reactivity of the nucleophiles and tertiary alcohols. The resulting products were able to convert to the corresponding α-triaryl acid 35, α-triaryl aldehyde 37 and β-triaryl alcohol 36 in reasonable yields. This method provided a good alternative for the synthesis of α-quaternary ketones or esters, as electron-deficient substituent such as fluorobenzene could be first installed onto the α position of tertiary alcohols, and halogenated indoles could serve as the nucleophiles as well. The use of cheap and easy to handle HClO4 (70%, aq.) to catalyze both arylation reactions is practical, but how to develop these reactions into catalytic asymmetric versions still remains a formidable challenge.

Scheme 22

Scheme 23

Tandem Friedel–Crafts/lactonization sequence.

6040 | Org. Biomol. Chem., 2014, 12, 6033–6048

2.2.

C–N bond formation

The direct conversion of tertiary alcohols to α-tertiary amines or the corresponding amides is of high synthetic value. In this context, the acid catalyzed Ritter reaction is an important C–N bond formation reaction, and obvious progress has been made in the synthesis of amides from tertiary alcohols and nitriles.38

Arylation of α-hydroxy esters or ketones.


View Article Online



Traditional methods involved the use of a large excess of acid. An early example reported in 1963 by Kaluszyner and Bergmann was the use of a large amount of concentrated H2SO4 to promote the Ritter reaction of diaryltrihalomethylcarbinols 38 and MeCN or benzonitrile to prepare the corresponding acetamide or benzamide in excellent yields (Scheme 24).39 Generally, carbenium ions were involved as intermediates in the Ritter reaction, and substituents which can stabilize the intermediate would facilitate this reaction. Most of the established catalytic Ritter reactions were limited to alcohols with α-electron-donating groups. In 2006, Hu et al. studied the Ritter reaction of tertiary α-CF2H carbinols 41 with acetonitrile in the presence of excess 98% concentrated H2SO4 to afford the corresponding amides 42 bearing a tetrasubstituted carbon centre in high yields (Scheme 25).40 Despite the above achievements, the use of a catalytic amount of acid to catalyze the Ritter reaction is highly desirable. In 2012, with our interest in the efficient synthesis of fully substituted aminooxindoles, we developed a Ritter reaction of 3-substituted 3-hydroxyoxindoles 1 with nitriles 39 using a catalytic amount of HClO4 (Scheme 26).34 Various 3-hydroxyoxindoles 1 with electron-donating or electron-withdrawing substituents at different positions on the aromatic rings could readily react with aliphatic, vinyl or aromatic nitriles to give the desired 3-substituted-3-aminooxindoles 43 in good to excellent yields. Accordingly, a variety of functional

Scheme 24

Ritter reaction of tertiary alcohols.

Scheme 25

Ritter reaction of tertiary α-CF2H alcohols.

Scheme 26

Ritter reaction of 3-hydroxyoxidoles.


Review

groups such as aldehyde, vinyl, cyclopropyl and ester groups could be introduced onto the amide moiety at the C3 position of oxindole. The adduct 43a, derived from acrylonitrile, could serve as a Michael acceptor to be converted to 44 in 83% yield, which further increased the diversity of the amide moiety at the C3 position. The azidation of alcohols represents an alternative powerful route to access amines. In 2012, Rueping et al. developed a Agcatalyzed direct azidation of allylic alcohols using TMSN3 (Scheme 27).41a A number of tertiary allylic alcohols could be readily transformed to the corresponding allylic azides in high to excellent yields and regioselectivities in the presence of only 5 mol% of AgOTf at room temperature. By combining this silver catalyzed process with a Pd/C catalyzed hydrogenation, a one-pot procedure was developed for the synthesis of the primary amine 47 from the tertiary alcohol 45a and TMSN3. α-Azidoketones are a type of important synthon for the synthesis of amines, nitrenes and heterocycles, and the direct azidation of α-hydroxyketones is a straightforward strategy. In 2013, Singh et al. disclosed an InBr3 catalyzed direct azidation of tertiary α-hydroxyketones 48 to α-azidoketones 49 using TMSN3 (Scheme 28).41b While the reaction of secondary alcohols such as benzoin and furoin with TMSN3 gave the corresponding trimethylsilyl protected benzoin or furoin, rather than the azidative product, the azidation of phenyl benzoin (2-hydroxy-1,2,2-triarylethanones) proceeded smoothly. This information indicated the crucial role of the aryl group and

Scheme 27

AgOTf catalyzed azidation of tertiary alcohols.

Scheme 28

InBr3 catalyzed direct azidation.

Org. Biomol. Chem., 2014, 12, 6033–6048 | 6041

View Article Online


Review


stereoelectronic factors towards azidation. This protocol was workable towards both the benzhydrols and 1,1,2-triphenylethanol, suggesting that the carbonyl group in the α-hydroxyketones had a minimal influence on the azidation. As the preactivation of α-hydroxyketones prior to azidation was avoided, together with the use of only 2 mol% of InBr3 as the catalyst, the usefulness of this protocol was very attractive. Along with the synthesis of α-carbolines via a formal [3 + 3] cycloaddition reaction, Wang and Ji also reported that γ-carboline derivatives could be synthesized from 2-hydroxy-2-(1Hindolyl-3-yl)-1H-indene-1,3(2H)-dione 50 (Scheme 29).32 In this process, I2 as the catalyst afforded the desired product in much higher yield than p-TsOH or InCl3. Under the optimized conditions, a variety of γ-carboline derivatives 51 was obtained in high to excellent yields. It was proposed that indolyl alcohols were activated by I2 to give the carbocation intermediate I, which was attacked by the enaminone 24 to give the 1,4addition intermediate II. The subsequent intramolecular 1,2addition of enamine to iminium gave the intermediate III, which was further oxidized to the desired formal [3 + 3] cyclization product 51. Usually, tertiary alcohols and their derivatives are reluctant to participate in a SN2 reaction; they either fail to react or produce stereochemical mixtures of products, which is in contrast to the fact that primary and secondary alcohols are viable precursor substrates for SN2 reaction, with predictable inversion of stereochemistry. However, Shenvi et al. recently developed a remarkable protocol for the stereoinversion of tertiary alcohols to tertiary-alkyl isonitriles (Scheme 30),42 which was initiated by the conversion of enantioenriched tertiary alcohols to the corresponding trifluoroacetates I that underwent solvolysis in TMSCN to give the desired isonitriles 52 with the inversed configuration, under the catalysis of 3 mol% of Sc(OTf )3. By this method, the percentage inversion of tertiary alcohols such as 52a, with a sole stereocentre, was around 90%, accounting for the enantiomeric purity of the alcohol.

Scheme 29

[3 + 3] cycloaddition reaction to γ-carbolines.

6042 | Org. Biomol. Chem., 2014, 12, 6033–6048

Scheme 30

Stereoinversion of tertiary alcohols.

Naturally occurring marine terpenes such as 52b and 52c could be readily prepared by this stereochemical inversion strategy. Noticeably, the procedure enabled the synthesis of α-tertiary amines featuring three different alkyl groups and their derivatives, such as 53a, naturally occurring cadinenes 53b and 53c. This protocol was chemoselective for tertiarytrifluoroacetyl esters in preference to secondary or primary alcohols, as evidenced in the case of 52c. The detailed mechanism for the solvolysis step needs further investigation. It should be noted that this is a rare example of catalytic functionalization of tertiary alcohols via a SN2 reaction. 2.3

C–O/C–S bond formation

Apart from C–C and C–N bond forming reactions, the corresponding substitution reaction of tertiary alcohols using O- or S-based nucleophiles has also been investigated. However, it is to some extent difficult to realize a metal catalyzed reaction involving a sulfur-containing reagent for the possible catalyst poisons, due to the strong coordinating properties of sulfur. In 2002, Hidai and Uemura utilized a novel cationic diruthenium complex 54 to catalyze the substitution of propargylic alcohols 12 using thiols to prepare propargylic sulfides 56 (Scheme 31).43 Tertiary alcohols such as 12d and 12e readily reacted with the thiol 55a to give the desired sulfides 56a and 56b in good yields with complete regioselectivity. In 2006, Firouzabadi and Iranpoor found that a silica gel supported ZrCl4 catalyzed S-alkylation of thiols with diverse tertiary alcohols to give different thioethers under solvent-free

Scheme 31

Ru-catalyzed propargylic substitution.


View Article Online



Scheme 32

ZrCl4-catalyzed S-alkylation of thiols.

conditions (Scheme 32).44 Both aliphatic and aromatic thiols were viable substrates, giving the corresponding products in high to excellent yields. This method is also applicable for the preparation of dithioethers. However, the loading of ZrCl4 was as high as 50 mol%. In the Ga(OTf )3 catalyzed direct substitution of alcohols with sulfur nucleophiles to afford thioethers, developed by Han and Wu in 2010, an example using the tertiary alcohol 58 to react with diethyl phosphorothioic acid 55b was reported, yielding the thioether 57a in 79% yield (Scheme 33).45 In 2006, Zhan et al. reported the use of 5 mol% FeCl3 to catalyze the nucleophilic substitution of propargylic alcohols for the C–C, C–O, C–S and C–N bond formation reactions. In this work, two examples of using alcohols to react with propargylic alcohol 12f to prepare tertiary ethers were also tried and acceptable yields were obtained (Scheme 34).46 Recently, we further utilized HClO4 as the catalyst to develop a highly efficient metal-free SN1-type substitution reaction of 3-hydroxyoxindoles 1 using thiols 55 or alcohols to construct 3-substituted 3-(alkylthio)oxindoles or 3-alkoxyoxindoles, with catalyst loading down to 0.5 mol% (Scheme 35).47 Both 3-aryl- and 3-alkyl-3-hydroxyoxindoles reacted with thiols or alcohols to give the desired products in good to excellent yields. Starting from isatins, allyltrimethylsilane and thiols, a Hg(ClO4)2·3H2O catalyzed tandem Sakurai–Hosomi/substitution reaction was also developed. The obtained products could be converted into spirocyclicoxindoles 60, 61 and the tricylic compound 62.

Scheme 33

Scheme 34

Review

Ga(OTf )3 catalyzed substitution of tertiary alcohols.

FeCl3 catalyzed substitution of propargylic alcohols.


Scheme 35

S/O-Alkylation of 3-hydroxyoxindoles.

Scheme 36

Comparison of direct and indirect substitution.

On the other hand, we found that in the presence of HClO4, the direct substitution of 3-phenyl-3-hydroxyoxindole 1e using phenthiol afforded the Friedel–Crafts adduct 3y in 83% yield, while the indirect substitution reported by Zhu and coworkers, involving DBU catalyzed trichloroacetimidate I formation and subsequent diphenylphosphoric acid catalyzed substitution, provided the sulfide 3s in 85% yield (Scheme 36). Although the detailed mechanism to account for the alteration of the reaction path was not clear at this moment, this unexpected result suggested that the direct and indirect reactions might proceed with different reaction intermediates, a cationic intermediate with the C3 benzylic carbocation or the 1-alkyl-2oxo-2H-indol-1-ium intermediate II shown in Scheme 17, or different Brønsted acids (HClO4 vs. TFA) might play a role.

3. Asymmetric reactions The catalytic asymmetric functionalization of tertiary alcohols to furnish a quaternary stereogenic carbon centre is unambiguously a formidable but highly rewarding research. With the development of chiral phosphoric acid catalysis49 and asymmetric enamine catalysis,50 the initial promising achievements have been made and applied to the total synthesis of natural products, which highlighted the great potential of this atom-economical synthetic strategy.

Org. Biomol. Chem., 2014, 12, 6033–6048 | 6043

View Article Online


Review


In 2008, M. Rueping et al. found that the chiral phosphoric acid 63 could catalyze Friedel–Crafts alkylation between the tertiary alcohol 1g and indole to afford atropisomeric bisindole 64 with 56% ee, although the yield was not given (Scheme 37).51 Presumably, the initial dehydration of the alcohol 1g by a chiral acid produced the carbocationic intermediate I or II, ion-paired with a chiral counter anion, which provided face discrimination for the following nucleophilic substitution. A major breakthrough in this field was made by the Gong group in 2012 (Scheme 38).52 They disclosed that the use of 10 mol% of phosphoric acid 66a enabled a highly enantioselective substitution reaction of 3-substituted 3-hydroxyoxindoles 1 with enecarbamates 65, furnishing enantioenriched quaternary oxindoles 3 in 72–92% yield with 90–96% ee. This protocol had a broad substrate scope for differently substituted 3-indolyl hydroxyoxindoles and a variety of enecarbamate nucleophiles. For a better understanding of the excellent enantioselectivity of this reaction, DFT calculations were conducted. It was believed that a vinylogous iminium intermediate formed

Scheme 37

63 Catalyzed asymmetric Friedel–Crafts reaction.

Scheme 38

66a Catalyzed asymmetric substitution reaction.

6044 | Org. Biomol. Chem., 2014, 12, 6033–6048

from the initial dehydration, with the cis-isomer being more stable than the trans-isomer. In addition, the phosphoric acid played a bifunctional role in simultaneously activating the vinylogous iminium and the enecarbamate through the H-bonding interaction, which also organized the Michael addition of enecarbamate to the iminium intermediate in a favourable intramolecular fashion, leading to the observed excellent enantioselective control. The importance of this protocol was demonstrated by the facile catalytic enantioselective construction of the 3a,3a′-bispyrrolidino[2,3-b]indoline core for the total synthesis of (+)-folicanthine (Scheme 39). The use of 10 mol% 66a facilitated the reaction of 3-hydroxyoxindole 1h and enecarbamate 65a to afford 67 in 82% yield with 90% ee. The following dimethylation and Beckmann rearrangement gave the key intermediate 70. Accordingly, folicanthine was obtained from 3-hydroxyindole 1h in 12 steps, with a 3.7% overall yield. Also in 2012, Guo and Peng reported a chiral phosphoric acid catalyzed enantioselective direct α-alkylation of 3-indolyl 3-hydroxy-3-indolyloxindoles 1 using simple ketones as nucleophiles (Scheme 40).53 The desired 3-indolyloxindoles 72 with a C3 quaternary center were achieved in up to 98% yield with up to 97% ee, and a broad range of substituted 3-hydroxy-3-indolyloxindoles, along with cyclic or acyclic ketones, were viable substrates in this protocol. The free N–H bond of the 3-indolyl moiety on the hydroxyoxindole was crucial for the high yield and excellent stereoselectivities in this protocol. For example, when the reaction was catalyzed by 10 mol% of acid 66b in toluene for 48 hours, hydroxyoxindole 1d reacted with cyclohexanone to give the desired product in 80% yield, 95 : 5 dr with 91% ee, whereas the N-Bn protected analogue afforded the corresponding product with much inferior result (23% yield, 97 : 3 dr with 34% ee). Based on this result, it was proposed that 3-hydroxy-3-indolyloxindole, dehydrated by a chiral acid, formed a vinylogous iminium intermediate, and the

Scheme 39

Total synthesis of (+)-folicanthine.


View Article Online



Review

Scheme 42

Scheme 40

Asymmetric α-alkylation of ketones.

bifunctional phosphoric acid interacted with both the iminium and enol form of the ketone through the H-bonding interaction, allowing the enol to attack the vinylogous iminium on the Re face to give the alkylated product 72. Later in 2013, Gong et al. further combined 10 mol% chiral primary amine 74 derived from a quinine with 30% chiral phosphoric acid 66c to establish a highly enantioselective alkylation of 3-indolyl 3-hydroxyoxindoles 1 using the enolizable OPMP-acetaldehyde 73a, providing quaternary oxindoles 73 with high dr values and excellent ee values (Scheme 41).54 Once again, this nice asymmetric alkylation was applied to the enantioselective total synthesis of (+)-gliocladin C in 12

Scheme 41

Asymmetric catalytic alkylation reaction.


Total synthesis of (+)-gliocladin C.

steps with overall 19% yield, starting from 3-hydroxyoxindole 1h (Scheme 42). It should be noted that both the chiral phosphoric acid and chiral primary amine were indispensible for the high yield and stereoselectivities for the synthesis of the key building block 75a in 80% yield, with 8 : 1 dr and 94% ee, which was obviously much better than that obtained using TFA as the acid catalyst (47% yield, 77% ee and 4 : 1 dr for 75a). In 2013, Wang and Ji found that the mere use of asymmetric enamine catalysis was also able to realize asymmetric α-alkylation of aldehydes with tertiary 3-hydroxyoxindoles in aqueous media (Scheme 43).55 MacMillan’s catalyst 77 allowed the alkylation of a variety of aldehydes using 3-hydroxyoxindoles 1, with electron-donating or weak electron-withdrawing groups on the indole fragments, to work well to give the product 78 in good yields and enantioselectivity, but the diastereoselectivity is not satisfactory. Based on 3-indolyl 3-hydroxyoxindoles, the first catalytic asymmetric formal [3 + 3] cycloaddition using an azomethine ylide generated in situ from aldehydes 73 and the aminoester 79 was achieved by Shi and Tu in 2014 (Scheme 44).56 It should be noted that the synthesis of six-membered heterocycles via cycloaddition involving azomethine ylides was rarely explored, although the dipolar cycloaddition of azomethine

Scheme 43

Asymmetric α-alkylation of aldehydes.

Org. Biomol. Chem., 2014, 12, 6033–6048 | 6045

View Article Online


Review


ponding catalytic enantioselective protocols are limited to the highly reactive 3-indolylmethanols on the basis of chiral phosphoric acid catalysis or asymmetric enamine catalysis. Identifying other effective catalyst models and enlarging the scope of tertiary alcohols for the development of catalytic asymmetric protocols based on tertiary alcohols are for sure the state of the art in this field. As can be expected, with the development of new efficient synthetic methodologies and chiral catalysts, the catalytic functionalization of tertiary alcohols will be fueled and more practical methods will come out and demonstrate their utility in drug and natural product synthesis.

Acknowledgements Scheme 44

A formal [3 + 3] cycloaddition.

ylides to five-membered heterocycles was studied extensively. By this method, structurally diverse spiro[indoline-3′4-pyridoindoles] 80 with two stereogenic centers including one allcarbon quaternary center were achieved in up to 93% yield with excellent enantioselectivities, albeit with moderate dr values. Once again, the free N–H bond of the indole moiety of the hydroxyoxindole was found to be very important for the high efficiency of this reaction, as the corresponding N-Bn-protected 3-indolylmethanol afforded only a Michael adduct in low yield, rather than the desired cycloaddition product, suggesting that the reaction was initiated by a Michael addition. The authors proposed that the reaction proceeded via the formation of the vinyliminium intermediate I from isatin-derived 3-indolylmethanol in the presence of the phosphoric acid 66d, which possibly reacted with the azomethine ylide generated in situ from the condensation of the aldehyde 73 and the amino ester 79 via a sequential Michael addition/ Pictet–Spengler reaction to give the six-membered heterocyclic product. Here, the phosphoric acid 66d acted as a Brønsted acid/Lewis base bifunctional catalyst to simultaneously activate both reaction partners through H-bonding interactions.

4.

Conclusions

The last decade has witnessed much progress in the catalytic direct functionalization of tertiary alcohols via C–C and C–heteroatom bond formation reactions. Impressive achievement has also been made in the development of catalytic asymmetric versions and applied to the total synthesis of natural products. However, despite the great potential of this atom-economical synthetic methodology in the construction of all-carbon and heteroatom-containing quaternary carbons, the corresponding research is still at its infancy. Not only the reaction types but also the substrate scope in some protocols is still very limited. In addition, how to enable tertiary alcohols with one or more electron-withdrawing groups to be efficiently functionalized still remains a challenge. Currently, the corres-

6046 | Org. Biomol. Chem., 2014, 12, 6033–6048

Financial support from the 973 program (2011CB808600), NSFC (21172075, 21222204), the Ministry of Education (NCET-11-0147 and PCSIRT) and the Program of SSCS (13XD1401600) is appreciated.

Notes and references 1 (a) S. F. Martin, Tetrahedron, 1980, 36, 419; (b) K. Fuji, Chem. Rev., 1993, 93, 2037; (c) J. Christoffers and A. Mann, Angew. Chem., Int. Ed., 2001, 40, 4591; (d) I. Denissova and L. Barriault, Tetrahedron, 2003, 59, 10105; (e) V. Farina, J. T. Reeves, C. H. Senanayake and J. J. Song, Chem. Rev., 2006, 106, 2734. 2 (a) F. Zhou, Y.-L. Liu and J. Zhou, Adv. Synth. Catal., 2010, 352, 1381; (b) K. Shen, X. Liu, L. Lin and X. Feng, Chem. Sci., 2012, 3, 327; (c) A. Kumar and S. S. Chimni, RSC Adv., 2012, 2, 9748; (d) Y.-L. Liu, F. Zhu, C.-H. Wang and J. Zhou, Chin. J. Org. Chem., 2013, 33, 1595; (e) Z.-Y. Cao, Y.-H. Wang, X.-P. Zeng and J. Zhou, Tetrahedron Lett., 2014, 55, 2571–2584. 3 Y. Li, X. Li and J.-P. Cheng, Adv. Synth. Catal., 2014, 356, 1172. 4 (a) S. Kobayashi, Y. Mori, J. S. Fossey and M. M. Salter, Chem. Rev., 2011, 111, 2626; (b) P. G. Cozzi, R. Hilgraf and N. Zimmermann, Eur. J. Org. Chem., 2007, 5969; (c) M. Shibasaki and M. Kanai, Chem. Rev., 2008, 108, 28533; (d) O. Riant and J. Hannedouche, Org. Biomol. Chem., 2007, 5, 873. 5 (a) J. Wang, X. Liu and X. Feng, Chem. Rev., 2011, 111, 6947; (b) H. Gröger, Chem. Rev., 2003, 103, 2795; (c) C. Cativiela and M. D. Díaz-de-Villegas, Tetrahedron: Asymmetry, 1998, 9, 3517. 6 See for examples: (a) B. S. Jensen, CNS Drug Rev., 2002, 8, 353; (b) V. V. Vintonyak, K. Warburg, H. Kruse, S. Grimme, K. Hübel, D. Rauh and H. Waldmann, Angew. Chem., Int. Ed., 2010, 49, 5902; (c) I. Gomez-Monterrey, A. Bertamino, A. Porta, A. Carotenuto, S. Musella, C. Aquino, I. Granata, M. Sala, D. Brancaccio, D. Picone, C. Ercole, P. Stiuso, P. Campiglia, P. Grieco, P. Ianelli, B. Maresca and E. Novellino, J. Med. Chem., 2010, 53, 8319; (d) R. Sakhuja,


View Article Online



7 8

9

10

11

12 13 14

15 16 17 18 19

20 21 22 23 24 25

S. S. Panda, L. Khanna, S. Khurana and S. C. Jain, Bioorg. Med. Chem. Lett., 2011, 21, 5465; (e) Y.-L. Liu, J.-S. Yu and J. Zhou, Asian J. Org. Chem., 2013, 2, 194; (f ) J.-A. Ma and S. Li, Org. Chem. Front., 2014, 1, DOI: 10.1039/ C4QO00078A; (g) Y.-L. Liu, F.-M. Liao, Y.-F. Niu, X.-L. Zhao and J. Zhou, Org. Chem. Front., 2014, 1, DOI: 10.1039/ C4QO00126E. E. J. Corey and A. Guzman-Perez, Angew. Chem., Int. Ed., 1998, 37, 388, and references therein. (a) C. J. Douglas and L. E. Overman, Proc. Natl. Acad. Sci. U. S. A., 2004, 101, 5363; (b) B. M. Stoltz, Nature, 2008, 455, 323; (c) J. P. Das and I. Marek, Chem. Commun., 2011, 47, 4593. (a) B. M. Trost, Science, 1991, 254, 1471; (b) R. A. Sheldon, Pure Appl. Chem., 2000, 72, 1233; (c) P. Anastas and N. Eghbali, Chem. Soc. Rev., 2010, 39, 301. (a) K. C. Nicolaou, M. Bella, D. Y.-K. Chen, X.-H. Huang, T.-T. Ling and S. A. Snyder, Angew. Chem., Int. Ed., 2002, 41, 3495; (b) K. C. Nicolaou, D. Y.-K. Chen, X.-H. Huang, T.-T. Ling, M. Bella and S. A. Snyder, J. Am. Chem. Soc., 2004, 126, 12888. A. Natarajan, Y.-H. Fan, H. Chen, Y.-H. Guo, J. Iyasere, F. Harbinski, W. J. Christ, H. Aktas and J. A. Halperin, J. Med. Chem., 2004, 47, 1882. K. C. Nicolaou, Q. Kang, T. R. Wu, C. S. Lim and D. Y.-K. Chen, J. Am. Chem. Soc., 2010, 132, 7540. R. R. Naredla and D. A. Klumpp, Chem. Rev., 2013, 113, 6905. (a) M. Rueping and B. J. Nachtsheim, Beilstein J. Org. Chem., 2010, 6, DOI: 10.3762/bjoc.6.6; (b) S.-L. You, Q. Cai and M. Zeng, Chem. Soc. Rev., 2009, 38, 2190; (c) M. Bandini and A. Eichholzer, Angew. Chem., Int. Ed., 2009, 48, 9608; (d) M. Zeng and S.-L. You, Synlett, 2010, 1289. M. Rueping, B. J. Nachtsheim and W. Ieawsuwan, Adv. Synth. Catal., 2006, 348, 1033. S. Shirakawa and S. Kobayashi, Org. Lett., 2007, 9, 311. U. Jana, S. Maiti and S. Biswas, Tetrahedron Lett., 2007, 48, 7160. J. A. McCubbin and O. V. Krokhin, Tetrahedron Lett., 2010, 51, 2447. (a) R. Sanz, D. Miguel, J. M. Álvarez-Gutiérrez and F. Rodríguez, Synlett, 2008, 975; (b) R. Sanz, D. Miguel, A. Martínez, M. Gohain, P. García-García, M. A. FernándezRodríguez, E. Álvarez and F. Rodríguez, Eur. J. Org. Chem., 2010, 7027. M. Niggemann and M. J. Meel, Angew. Chem., Int. Ed., 2010, 49, 3684. M. Gohain, C. Marais and B. C. B. Bezuidenhoudt, Tetrahedron Lett., 2012, 53, 4704. B. Nammalwar and R. A. Bunce, Tetrahedron Lett., 2013, 54, 4330. G. Chen, Z. Wang, J. Wu and K.-L. Ding, Org. Lett., 2008, 10, 4573. V. J. Meyer and M. Niggemann, Eur. J. Org. Chem., 2011, 3671. S.-Y. Wang and S.-J. Ji, Tetrahedron, 2006, 62, 1527.


Review

26 (a) D. B. England, G. Merey and A. Padwa, Org. Lett., 2007, 9, 3805; (b) D. B. England, G. Merey and A. Padwa, Heterocycles, 2007, 74, 491. 27 (a) Z.-Y. Cao, X. Wang, C. Tan, X.-L. Zhao, J. Zhou and K. Ding, J. Am. Chem. Soc., 2013, 135, 8197; (b) F. Zhou, C. Tan, J. Tang, Y.-Y. Zhang, W.-M. Gao, H.-H. Wu, Y.-H. Yu and J. Zhou, J. Am. Chem. Soc., 2013, 135, 10994; (c) Y.-L. Liu, B.-L. Wang, J.-J. Cao, L. Chen, Y.-X. Zhang, C. Wang and J. Zhou, J. Am. Chem. Soc., 2010, 132, 15176; (d) Y.-L. Liu, X. Wang, Y.-L. Zhao, F. Zhu, X.-P. Zeng, L. Chen, C.-H. Wang, X.-L. Zhao and J. Zhou, Angew. Chem., Int. Ed., 2013, 52, 13735; (e) M. Ding, F. Zhou, Y.-L. Liu, C.-H. Wang, X.-L. Zhao and J. Zhou, Chem. Sci., 2011, 2, 2035; (f ) Z.-Y. Cao, F. Zhou, Y.-H. Yu and J. Zhou, Org. Lett., 2013, 15, 42; (g) Z.-Y. Cao, Y. Zhang, C.-B. Ji and J. Zhou, Org. Lett., 2011, 13, 6398; (h) Y.-L. Liu and J. Zhou, Chem. Commun., 2012, 48, 1919; (i) F. Zhou, X.-P. Zeng, C. Wang, X.-L. Zhao and J. Zhou, Chem. Commun., 2013, 49, 2022; ( j) Z.-Q. Qian, F. Zhou, T.-P. Du, B.-L. Wang, M. Ding, X.-L. Zhao and J. Zhou, Chem. Commun., 2009, 6753; (k) M. Ding, F. Zhou, Z.-Q. Qian and J. Zhou, Org. Biomol. Chem., 2010, 8, 2912; (l) F. Zhou, M. Ding, Y.-L. Liu, C.-H. Wang, C.-B. Ji, Y.-Y. Zhang and J. Zhou, Adv. Synth. Catal., 2011, 353, 2945; (m) J.-S. Yu, F. Zhou, Y.-L. Liu and J. Zhou, Beilstein J. Org. Chem., 2012, 8, 1360; (n) L. Chen, F. Zhu, H.-C. Wang and J. Zhou, RSC Adv., 2013, 3, 19880; (o) Y.-L. Liu and J. Zhou, Acta Chim. Sin., 2012, 70, 1451; ( p) Y-H. Wang, Z-Y. Cao, Y.-F. Niu, X.-L. Zhao and J. Zhou, Acta Chim. Sin., 2014, 72, DOI: 10.6023/A14040335. 28 F. Zhou, Z.-Y. Cao, J. Zhang, H.-B. Yang and J. Zhou, Chem. – Asian J., 2012, 7, 233. 29 S. Ghosh, L. K. Kinthada, S. Bhhnia and A. Bisai, Chem. Commun., 2012, 10132. 30 C. Piemontesi, Q. Wang and J.-P. Zhu, Org. Biomol. Chem., 2013, 11, 1533. 31 R. R. Naredla, E. K. Raja and D. A. Klumpp, Tetrahedron Lett., 2013, 54, 3245. 32 W.-J. Hao, S.-Y. Wang and S.-J. Ji, ACS Catal., 2013, 3, 2501. 33 L. K. Kinthada, S. Ghosh, S. De, S. Bhunia, D. Dey and A. Bisai, Org. Biomol. Chem., 2013, 11, 6984. 34 F. Zhou, M. Ding and J. Zhou, Org. Biomol. Chem., 2012, 10, 3178. 35 L. Chen, F. Zhou, T.-D. Shi and J. Zhou, J. Org. Chem., 2012, 77, 4354. 36 L. Chen and J. Zhou, Chem. – Asian J., 2012, 7, 2510. 37 Y.-C. Wu, H.-J. Li, L. Liu, N. Demoulin, Z. Liu, D. Wang and Y.-J. Chen, Adv. Synth. Catal., 2011, 353, 907. 38 For a recent review, see: A. Guérinot, S. Reymond and J. Cossy, Eur. J. Org. Chem., 2012, 19. 39 A. Kaluszyner, S. Blum and E. D. Bergmann, J. Org. Chem., 1963, 28, 3588. 40 J. Liu, C.-F. Ni, Y. Li, L.-J. Zhang, G.-Y. Wang and J.-B. Hu, Tetrahedron Lett., 2006, 47, 6753. 41 (a) M. Rueping, C. Vila and U. Uria, Org. Lett., 2012, 14, 768; (b) A. Kumar, R. K. Sharma, T. V. Singh and P. Venugopalan, Tetrahedron, 2013, 69, 10724.

Org. Biomol. Chem., 2014, 12, 6033–6048 | 6047

View Article Online


Review

42 S. V. Pronin, C. A. Reiher and R. A. Shenvi, Nature, 2013, 501, 195. 43 Y. Inada, Y. Nishibayashi, M. Hidai and S. Uemura, J. Am. Chem. Soc., 2002, 124, 15172. 44 H. Firouzabadi, N. Iranpoor and M. Jafarpour, Tetrahedron Lett., 2006, 47, 93. 45 X.-P. Han and J. Wu, Org. Lett., 2010, 12, 5780. 46 Z.-P. Zhan, J.-L. Yu, H.-J. Liu, Y.-Y. Cui, R.-F. Yang, W.-Z. Yang and J.-P. Li, J. Org. Chem., 2006, 71, 8298. 47 F. Zhu, F. Zhou, Z.-Y. Cao, C. Wang, Y.-X. Zhang, C.-H. Wang and J. Zhou, Synthesis, 2012, 3129. 48 B. Alcaide, P. Almendros and R. Rodriguez-Acebes, J. Org. Chem., 2006, 71, 2346. 49 (a) D. Uraguchi and M. Terada, J. Am. Chem. Soc., 2004, 126, 5356; (b) T. Akiyama, J. Itoh, K. Yokota and K. Fuchibe, Angew. Chem., Int. Ed., 2004, 43, 1566 for

6048 | Org. Biomol. Chem., 2014, 12, 6033–6048


50 51 52 53 54 55 56

reviews, see: (c) T. Akiyama, Chem. Rev., 2007, 107, 5744; (d) M. Terada, Synthesis, 2010, 1929. S. Mukhrjee, J. W. Yang, S. Hoffmann and B. List, Chem. Rev., 2007, 107, 5471. M. Rueping, B. J. Nachtsheim, S. A. Moreth and M. Bolte, Angew. Chem., Int. Ed., 2008, 47, 593. C. Guo, J. Song, J.-Z. Huang, P.-H. Chen, S.-W. Luo and L.-Z. Gong, Angew. Chem., Int. Ed., 2012, 51, 1046. L. Song, Q.-X. Guo, X.-C. Li, J. Tian and Y.-G. Peng, Angew. Chem., Int. Ed., 2012, 51, 1899. J. Song, C. Guo, A. Adele, H. Yin and L.-Z. Gong, Chem. – Eur. J., 2013, 19, 3319. Y. Zhang, S.-Y. Wang, X.-P. Xu, R. Jiang and S.-J. Ji, Org. Biomol. Chem., 2013, 11, 1933. F. Shi, R.-Y. Zhu, W. Dai, C.-S. Wang and S.-J. Tu, Chem. – Eur. J., 2014, 20, 2597.


Catalytic meta-selective C-H functionalization to construct quaternary carbon centres.

Catalytic enantioselective C-H functionalization of alcohols by redox-triggered carbonyl addition: borrowing hydrogen, returning carbon.

Catalytic asymmetric synthesis of CF3-substituted tertiary propargylic alcohols via direct aldol reaction of α-N3 amide.

Phosphinocyclodextrins as confining units for catalytic metal centres. Applications to carbon-carbon bond forming reactions.

Highly Chemoselective Catalytic Coupling of Substituted Oxetanes and Carbon Dioxide.

Asymmetric Synthesis of Tertiary Alcohols and Thiols via Nonstabilized Tertiary α-Oxy- and α-Thio-Substituted Organolithium Species.

A Fully Phosphane-Substituted Disilene.

Catalytic functionalization of methane and light alkanes in supercritical carbon dioxide.

Enantioselective formation of all-carbon quaternary stereocenters from indoles and tertiary alcohols bearing a directing group.

Direct catalytic olefination of alcohols with sulfones.

Catalytic stereodivergent functionalization of H2@C60.

Catalytic enantioselective bromoamination of allylic alcohols.

Chemoselective formation of unsymmetrically substituted ethers from catalytic reductive coupling of aldehydes and ketones with alcohols in aqueous solution.

Mitsunobu Reactions Catalytic in Phosphine and a Fully Catalytic System.

Reductive dismantling and functionalization of carbon nanohorns.

Catalytic, oxidant-free, direct olefination of alcohols using Wittig reagents.

Catalytic C6 functionalization of 2,3-disubstituted indoles by scandium triflate.

Solitary sclerosis: Experience from three French tertiary care centres.

Formal [4 + 1]-cycloaddition of homopropargyl alcohols to diazo dicarbonyl compounds giving substituted tetrahydrofurans.

Lithium binaphtholate-catalyzed enantioselective enyne addition to ketones: access to enynylated tertiary alcohols.

Second-trimester induced abortions in two tertiary centres in Rome.

Tertiary alcohols as substrates for S(N)2-like stereoinversion.

Catalytic hydrogenation of amino acids to amino alcohols with complete retention of configuration.

Catalytic Rearrangement of 2-Alkoxy Diallyl Alcohols: Access to Polysubstituted Cyclopentenones.