COMMUNICATION DOI: 10.1002/asia.201400135

Alkene Isomerization–Hydroarylation Tandem Catalysis: Indole C2Alkylation with Aryl-Substituted Alkenes Leading to 1,1-Diarylalkanes Takeshi Yamakawa and Naohiko Yoshikai*[a]

Abstract: A cobalt-N-heterocyclic carbene catalyst generated from CoBr2, imidazolium salt, and cyclohexylmagnesium bromide was found to promote the imine-directed C2-alkylation of indoles with nonconjugated arylalkenes through a tandem alkene isomerization–hydroarylation process, affording 1,1-diarylalkanes with exclusive regioselectivity. The feasibility of the tandem catalysis was demonstrated for allyl-, homoallyl-, and bishomoallylbenzene derivatives. The catalytic system is also applicable to a variety of b-substituted styrene derivatives. Mechanistic experiments using deuterium-labeled indole substrate and Grignard reagent provided insight into the cobalt-mediated C H activation step, which likely involves exchange of the C2-hydrogen atom of the former and the b-hydrogen atoms of the latter. Scheme 1. Transition metal-catalyzed tandem alkene isomerization–hydroarylation.

Alkene hydroarylation represents an atom-efficient approach to alkylation of aromatic compounds. In particular, hydroarylation involving chelation-assisted C H activation by a low-valent transition metal catalyst is attractive owing to a predictable regioselectivity.[1–5] However, the desired hydroarylation is sometimes hampered by the propensity of low-valent transition metal complexes for catalyzing isomerization of alkenes.[6] Indeed, isomerization to a thermodynamically more stable, but less reactive internal alkene is often the cause of less efficient or unsuccessful hydroarylation with terminal alkenes bearing allylic hydrogens.[2b, 3a,c, 7] In a few cases, isomerization of an internal alkene to a terminal one is followed by hydroarylation to afford a primary alkylation product, as exemplified by the rhodium-catalyzed reaction of an aromatic imine by Jun et al.[3e,f] and the cobalt-catalyzed reaction of a benzamide by Nakamura et al.,[4b] where anti-Markovnikov selectivity of the catalysts serves as the driving force (Scheme 1 a, b). We report here a new example of alkene isomerization–hydroarylation auto-tandem catalysis,[8] in which a cobalt-N-heterocyclic carbene (NHC)–Grignard catalytic system promotes C2-al-

kylation of an indole with nonconjugated arylalkenes to afford 1,1-diarylalkane derivatives with exclusive regioselectivity (Scheme 1 c).[9, 10] Mechanistic experiments have shed light on the unique role of the secondary alkyl Grignard reagent in the C H activation step. The present study initially focused on the reaction of aldimine 1 a, derived from indole-3-carboxaldehyde, with allylbenzene 2 a (Table 1). Through extensive screening of reaction conditions, a catalytic system consisting of CoBr2 (10 mol %), 1,3-bis(2,6-dimethylphenyl)imidazolium chloride (IXyl·HCl, 10 mol %), cyclohexylmagnesium bromide (100 mol %), and N,N,N’,N’-tetramethylethylenediamine (TMEDA, 2 equiv) was found to promote the reaction at room temperature, affording 1,1-diarylpropane derivative 3 a with exclusive regioselectivity in 87 % yield (entry 1). Replacement of IXyl·HCl with IMes·HCl or monodentate phosphine (PPh3, PCy3) led to a lower yield albeit with perfect regioselectivity (entries 2, 4, and 5). A bulkier NHC preACHTUNGREliACHTUNGREgand, IPr·HCl, was entirely ineffective (entry 3). The use of iPrMgBr or tBuCH2MgBr instead of CyMgBr resulted in a lower yield (entries 6 and 7), while the reaction was shut down with Me3SiCH2MgCl (entry 8). The yield of 3 a decreased when the reaction was performed with a lower amount of TMEDA (entry 9) or in its absence (entry 10). The yield also decreased with a reduced amount of allylbenzene (1.2 equiv) (entry 11). The catalyst loading (CoBr2, IXyl·HCl, CyMgBr, and TMEDA) could be reduced by half, albeit with a decreased efficiency (entry 12).

[a] T. Yamakawa, Prof. N. Yoshikai Division of Chemistry and Biological Chemistry School of Physical and Mathematical Sciences Nanyang Technological University Singapore 637371, Singapore Fax: (+ 65) 6791-1961 E-mail: [email protected] Supporting information for this article is available on the WWW under

Chem. Asian J. 2014, 9, 1242 – 1246


 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Takeshi Yamakawa and Naohiko Yoshikai

Table 1. Addition of 3-iminoindole 1 a to allylbenzene 2 a.[a]


Ligand [mol %]

RMgX [mol %]

Yield [%] (3 a:4 a)[b]

1 2 3 4 5 6 7 8 9[d] 10[e] 11[f] 12[g] 11[e,h,i] 12[e,h]

IXyl·HCl (10) IMes·HCl (10) IPr·HCl (10) PPh3 (20) PCy3 (10) IXyl·HCl (10) IXyl·HCl (10) IXyl·HCl (10) IXyl·HCl (10) IXyl·HCl (10) IXyl·HCl (10) IXyl·HCl (5) DMPU (600) DMPU (600)

CyMgBr (100) CyMgBr (100) CyMgBr (100) CyMgBr (100) CyMgBr (100) iPrMgBr (100) tBuCH2MgBr (100) Me3SiCH2MgCl (100) CyMgBr (100) CyMgBr (100) CyMgBr (100) CyMgBr (50) CyMgCl (100) tBuCH2MgBr (60)

87 (> 99:1)[c] 40 (> 99:1) 99:1) 27 (99:1) 29 (> 99:1) 13 (> 99:1) 99:1) 70 (> 99:1) 71 (> 99:1) 74 (> 99:1) 22 (46:54) 57 (5:95)[j]

[a] The reaction was performed on a 0.2 mmol scale. [b] Determined by GC or 1H NMR. [c] The isolated yield was 81 %. [d] 1 equiv of TMEDA was used. [e] TMEDA was omitted from the reaction. [f] 1.2 equiv of 2 a was used. [g] 5 mol % of CoBr2 and 1 equiv of TMEDA were used. [h] CoACHTUNGRE(acac)3 was used instead of CoBr2. The reaction time was 12 h. [i] Et2O was used as the solvent. [j] The isolated yield was 50 %.

The reaction with Nakamuras CoACHTUNGRE(acac)3–DMPU (N,N’dimethylpropyleneurea)–CyMgCl catalytic system in Et2O (cf. Scheme 1 b)[4b] afforded 3 a along with the linear alkylation product 4 a in 22 % overall yield with a modest ratio of about 1:1 (entry 13).[11] Notably, modification of this catalytic system allowed us to achieve regioselective formation of 4 a. Thus, by using tBuCH2MgBr and THF instead of CyMgCl and Et2O, respectively, the reaction afforded 4 a in 57 % yield with a regioisomeric ratio as high as 95:5 (entry 14). Typical rhodium(I)-based catalytic systems (RhClACHTUNGRE(PPh3)3, [RhClACHTUNGRE(coe)2]2-PCy3) proved to be much less effective (data not shown). Scheme 2 shows the scope of the isomerization–hydroarylation reaction with respect to the indole and allylbenzene derivatives. A series of indole substrates bearing different substituents on the benzene ring or the nitrogen atom participated in the reaction with parent allylbenzene 2 a, affording 1,1-diarylpropane derivatives 3 b–3 g in moderate to good yields with exclusive regioselectivity. A ketimine-bearing indole substrate was also amenable to the present reaction (see 3 h). Substituted allylbenzenes reacted with the substrate 1 a to exclusively afford branched products 3 i–3 m in good yields, with tolerance of an ortho substituent on the benzene ring (see 3 l and 3 m). The reaction of 2-allylthiophene was rather sluggish, yet afforded 1,1-diarylpropane derivative 3 n as the exclusive hydroarylation product in a low yield. Alkyl- and silyl-substituted allylbenzene derivatives also participated in the present isomerization–hydroar-

Chem. Asian J. 2014, 9, 1242 – 1246

Scheme 2. Addition of 3-iminoindoles to allylbenzene derivatives (0.2 mmol scale). [a] The reaction was performed at 60 8C for 12 h.

ylation reaction at an elevated temperature (60 8C) to afford 1,1-diarylalkanes 3 o and 3 p in moderate yields. The formation of 1,1-diarylpropanes apparently results from dual roles of the cobalt catalyst in promoting alkene isomerization[12] and hydroarylation. Thus, not unexpectedly, the present catalytic system allowed addition of 1 a to a variety of b-substituted styrene derivatives (Scheme 3). Both the E- and Z-isomers of b-methylstyrene reacted smoothly at room temperature to afford the product 3 a in good yields. The reaction of other b-alkylstyrenes, including those bearing benzyl- and THP ether moieties and the bulky cyclohexyl group, was achieved at 60 8C, affording 1,1-diarylalkanes 3 o and 3 q–3 s in moderate yields. We noted that, in the reaction of b-propylstyrene, a better yield was achieved with a 1:1 mixture of E and Z isomers than with the pure Eisomer, thus indicating a higher reactivity of the Z isomer. In agreement with this observation, the reaction of stilbene and b-trimethylsilylstyrene took place more smoothly with the corresponding Z-isomers, affording the adducts 3 t and 3 u in good yields. b,b-Dimethylstyrene failed to participate in the reaction, while 1,1-diphenylethylene underwent C C bond formation at the exomethylene carbon atom to afford the primary alkylation product 3 v in 25 % yield.


 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Takeshi Yamakawa and Naohiko Yoshikai

1 a to alkenes 6 and 7, thereby affording the primary alkylation products 4 w and 4 o, respectively, in modest yields with high regioselectivity (> 10:1). During the above investigations, we noted that the isomerization of allylbenzene to b-methylstyrene (E/Z > 95:5) completed before substantial conversion of the indole substrate 1 a. This observation indicates that olefin isomerization and hydroarylation take place through independent catalytic cycles. Indeed, in the absence of 1 a, the Co–IXyl– CyMgBr system caused isomerization of allylbenzene to bmethylstyrene within a few minutes. On the other hand, the isomerization of homoallylbenzene to b-ethylstyrene was much slower; even after substantial conversion of 1 a, we observed a mixture of but-2-en-1-ylbenzene and b-ethylstyrene. To gain insight into the mechanism of the present hydroarylation reaction, we performed a series of experiments using the C2-deuterated substrate [D]-1 a (Scheme 5). First,

Scheme 3. Addition of 3-iminoindole 1 a to b-substituted styrenes (0.2 mmol scale). [a] The reaction was performed at room temperature for 1 h.

The Co–IXyl–CyMgBr catalytic system also allowed the tandem isomerization–hydroarylation reaction of nonconjugated arylalkenes with aryl and alkenyl moieties separated by more than one carbon atom (Scheme 4). Thus, the reaction of 1 a with homoallylbenzene 6 and bishomoallylbenzene 7 afforded the corresponding 1,1-diarylalkane products 3 w and 3 o in moderate yields without formation of other regioisomers. Note that the reaction of 6 in the absence of TMEDA was sluggish (46 % yield) and was accompanied by the formation of a linear adduct 4 w (5 %). By contrast, the Co–DMPU–tBuCH2MgBr catalytic system (Table 1, entry 11) promoted the linear-selective addition of

Scheme 5. Reaction of C2-deuterated substrate [D]-1 a. Reaction conditions: a–c): CoBr2 (10 mol %), IXyl·HCl (10 mol %), CyMgBr (100 mol %), TMEDA (2 equiv), THF, rt, 3 min; d) CoBr2 (10 mol %), IXyl·HCl (10 mol %), CyMgBr (100 mol %), TMEDA (2 equiv), THF, 60 8C, 1 min. The number of protons on each carbon atom was determined by 1H NMR spectroscopy using the integration of the indole C4-H as the reference. The assignment of the diastereotopic protons Ha and Hb in 3 i is based on the assumption of a syn-hydroarylation mechanism.

the reactions of [D]-1 a with Z- and E-isomers of 1-methoxy-4-(prop-1-en-1-yl)benzene 5 i were quenched at the reaction time of 3 min to afford the hydroarylation product 3 i in yields of 74 % and 26 %, respectively (Scheme 5 a, b), again showing a higher reactivity of the Z-isomer over the E-isomer (cf. Scheme 3). 1H NMR spectroscopic analysis of the product revealed that the deuterium atom of [D]-1 a was mainly incorporated into the 2-position of 3 i in a diastereoselective fashion and that (Z)-5 i and (E)-5 i afforded opposite diastereomers. Note that the assignment of the relative

Scheme 4. Regiodivergent addition of 3-iminoindole 1 a to homoallylbenzene and bishomoallylbenzene.

Chem. Asian J. 2014, 9, 1242 – 1246


 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

stereochemistry of 3 i is tentative and is based on the assumption of a syn-hydroarylation mechanism. In the former reaction, the unreacted alkene was recovered as an E/Z mixture (1:1), whereas only the E-isomer was recovered in the latter. Next, the reaction of [D]-1 a with 4-methoxyallylbenzene 2 b under the same reaction conditions afforded 3 i in 59 % yield, where deuterium incorporation into the 2-position was observed to a modest extent (0.49D in total) with low diastereoselectivity (Scheme 5 c). Note also that the deuterium content of the unreacted indole substrate decreased to 77 %, while the unreacted alkene was recovered exclusively as (E)-5 i with minor (< 10 %) deuterium incorporation into the b-position. More strikingly, the reaction of [D]-1 a and 1homoallyl-4-methoxybenzene 8 resulted in virtually no significant deuterium incorporation into any position of the hydroarylation product 3 x (Scheme 5 d), while the deuterium content of the unreacted indole decreased to 54 %.[13] To probe the origin of the above anomalous observations, control experiments were performed with a modified catalytic system using [D7]-iPrMgBr instead of CyMgBr (Scheme 6). The reaction of 1 a alone resulted in significant incorporation of deuterium (40 %), presumably from the bposition of the Grignard reagent, into the C2 position of the recovered indole (42 % yield; Scheme 6 a). The rest of 1 a largely underwent reduction of the imine moiety by the Grignard reagent. On the other hand, the reaction of 2 b alone cleanly afforded (E)-5 i with only slight deuterium incorporation into the olefinic and allylic positions (Scheme 6 b). The reaction of 1 a and 2 b under the modified catalytic system resulted in partial and diastereoselective deuterium incorporation into the C2-Ha position of the hydroarylation product 3 i (Scheme 6 c).

Takeshi Yamakawa and Naohiko Yoshikai

The relevance of the present catalytic species and reaction pathways to the chemistry of well-defined cobalt-NHC complexes[14] remains unclear, and it appears premature to give an unambiguous interpretation of the above observations. Nevertheless, some mechanistic speculations can be made. Alkene isomerization typically proceeds through hydrometalation–b-hydride elimination or allylic C H activation-reductive elimination.[15] While the control experiment in Scheme 6b does not allow us to distinguish between these mechanisms, we speculate that the latter is more likely in light of a related Co–NHC–Grignard catalytic system for alkene isomerization.[12] Alkene hydroarylation with a lowvalent transition metal catalyst is generally considered to involve three major steps, that is, C H oxidative addition to the metal center, alkene insertion into the M H bond, and C C bond-forming reductive elimination.[1] While we also prefer this mechanistic framework,[4] the H/D exchange of 1 a caused by [D7]-iPrMgBr (Scheme 6 a) and the low deuterium incorporation into 3 x (Scheme 5 d) apparently indicate further mechanistic complexity. We speculate that the cobalt precatalyst and the secondary Grignard reagent give rise to a low-valent cobalt hydride species, and that this putative species undergoes exchange of hydrogen atoms with the indole substrate, thus interfering with the incorporation of the original C2-H atom into the hydroarylation product. The regio- and diastereoselective deuterium incorporation observed for (Z)- and (E)-5 i (Scheme 5 a, b) may point to regio- and stereoselective (most likely syn-selective) insertion of these alkenes into the Co H bond. Upon the alkene insertion, the resulting alkylcobalt intermediate would prefer to undergo reductive elimination rather than b-hydride elimination because the latter pathway would deteriorate the diastereoselectivity of the deuterium incorporation. In summary, we have reported on a Co–NHC–CyMgBr catalytic system for the indole alkylation reaction with arylsubstituted alkenes to afford 1,1-diarylalkane derivatives with exclusive regioselectivity. Allyl-, homoallyl-, and bishomoallylbenzene derivatives are amenable to the regioconvergent C C bond formation through a tandem alkene isomerization–hydroarylation sequence. The Co–DMPU– tBuCH2MgBr catalytic system allows complementary, linearselective alkylation. Deuterium-labeling experiments shed light on the involvement of the secondary alkyl Grignard reagent in the C H activation process. We speculate that the secondary alkyl Grignard reagents also play important roles in other relevant cobalt-catalyzed C H functionalization reactions.[4b, 10e, 16] Extension of the substrate scope is currently underway to establish a general synthetic approach to 1,1-diarylalkanes.[17]

Experimental Section Typical Procedure: Synthesis of 1-Methyl-2-(1-phenylpropyl)-1H-indole-3carbaldehyde (3 a)

Scheme 6. Control experiments using deuterated Grignard reagent. The number of protons on each carbon atom was determined by 1H NMR spectroscopy using the integration of the indole C4-H (a, c) or the methoxy CH3 (b) as the reference.

Chem. Asian J. 2014, 9, 1242 – 1246

To a solution of (E)-N-(4-methoxyphenyl)-1-(1-methyl-1H-indol-3-yl)methanimine (1 a, 52.9 mg, 0.20 mmol), allylbenzene (2 a, 35.5 mg,


 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

0.30 mmol), CoBr2 (0.1 m solution in THF, 0.2 mL, 0.02 mmol), 1,3bis(2,6-dimethylphenyl)-1H-imidazol-3-ium chloride (6.3 mg, 0.02 mmol), and TMEDA (60 mL, 0.4 mmol) in THF (0.03 mL) was added CyMgBr (0.46 m in THF, 0.44 mL, 0.2 mmol) at room temperature. The resulting mixture was stirred for 1 h, followed by quenching with water (0.5 mL). After addition of THF (1.0 mL) and 3 m HCl (0.4 mL), the mixture was stirred for another 1 h and then extracted with EtOAc (3  2 mL). The combined organic layer was dried over Na2SO4 and concentrated under reduced pressure. The crude material was purified by silica gel chromatography (n-hexane/EtOAc = 20:3) to afford 3 a as an orange solid (45.8 mg, 83 % yield)



Acknowledgements [7] This work was supported by the Singapore National Research Foundation (NRF-RF2009-05), Nanyang Technological University, and JST, CREST.

[8] [9]

Keywords: alkenes · alkylation · C H functionalization · cobalt · indoles [10]

[1] For reviews, see: a) D. A. Colby, R. G. Bergman, J. A. Ellman, Chem. Rev. 2010, 110, 624; b) F. Kakiuchi, T. Kochi, Synthesis 2008, 3013. [2] For ruthenium catalysis, see: a) S. Murai, F. Kakiuchi, S. Sekine, Y. Tanaka, A. Kamatani, M. Sonoda, N. Chatani, Nature 1993, 366, 529; b) F. Kakiuchi, S. Sekine, Y. Tanaka, A. Kamatani, M. Sonoda, N. Chatani, S. Murai, Bull. Chem. Soc. Jpn. 1995, 68, 62; c) M. Sonoda, F. Kakiuchi, A. Kamatani, N. Chatani, S. Murai, Chem. Lett. 1996, 109; d) F. Kakiuchi, M. Yamauchi, N. Chatani, S. Murai, Chem. Lett. 1996, 111; e) M. Sonoda, F. Kakiuchi, N. Chatani, S. Murai, Bull. Chem. Soc. Jpn. 1997, 70, 3117; f) F. Kakiuchi, T. Sato, T. Tsujimoto, M. Yamauchi, N. Chatani, S. Murai, Chem. Lett. 1998, 1053; g) R. Martinez, R. Chevalier, S. Darses, J. P. Genet, Angew. Chem. Int. Ed. 2006, 45, 8232; Angew. Chem. 2006, 118, 8412; h) R. Martinez, M. O. Simon, R. Chevalier, C. Pautigny, J. P. Genet, S. Darses, J. Am. Chem. Soc. 2009, 131, 7887; i) F. Kakiuchi, T. Kochi, E. Mizushima, S. Murai, J. Am. Chem. Soc. 2010, 132, 17741. [3] For rhodium catalysis, see: a) C. P. Lenges, M. Brookhart, J. Am. Chem. Soc. 1999, 121, 6616; b) C.-H. Jun, J. B. Hong, Y. H. Kim, K. Y. Chung, Angew. Chem. Int. Ed. 2000, 39, 3440; Angew. Chem. 2000, 112, 3582; c) Y.-G. Lim, J.-S. Han, S.-S. Yang, J. H. Chun, Tetrahedron Lett. 2001, 42, 4853; d) R. K. Thalji, K. A. Ahrendt, R. G. Bergman, J. A. Ellman, J. Am. Chem. Soc. 2001, 123, 9692; e) C.-H. Jun, C. W. Moon, J.-B. Hong, S.-G. Lim, K.-Y. Chung, Y.-H. Kim, Chem. Eur. J. 2002, 8, 485; f) S.-G. Lim, J.-A. Ahn, C.-H. Jun, Org. Lett. 2004, 6, 4687; g) R. K. Thalji, J. A. Ellman, R. G. Bergman, J. Am. Chem. Soc. 2004, 126, 7192; h) R. K. Thalji, K. A. Ahrendt, R. G. Bergman, J. A. Ellman, J. Org. Chem. 2005, 70, 6775; i) H. Harada, R. K. Thalji, R. G. Bergman, J. A. Ellman, J. Org. Chem. 2008, 73, 6772. [4] For cobalt catalysis, see: a) K. Gao, N. Yoshikai, J. Am. Chem. Soc. 2011, 133, 400; b) L. Ilies, Q. Chen, X. Zeng, E. Nakamura, J. Am.

Chem. Asian J. 2014, 9, 1242 – 1246

[11] [12] [13]


[15] [16]


Takeshi Yamakawa and Naohiko Yoshikai

Chem. Soc. 2011, 133, 5221; c) K. Gao, N. Yoshikai, Angew. Chem. Int. Ed. 2011, 50, 6888; Angew. Chem. 2011, 123, 7020; d) Z. Ding, N. Yoshikai, Beilstein J. Org. Chem. 2012, 8, 1536; e) P.-S. Lee, N. Yoshikai, Angew. Chem. Int. Ed. 2013, 52, 1240; Angew. Chem. 2013, 125, 1278; f) Z. Ding, N. Yoshikai, Angew. Chem. Int. Ed. 2013, 52, 8574; Angew. Chem. 2013, 125, 8736; g) J. Dong, P.-S. Lee, N. Yoshikai, Chem. Lett. 2013, 42, 1140. For other transition metal catalysis, see: a) Y. Kuninobu, Y. Nishina, K. Okaguchi, M. Shouho, K. Takai, Bull. Chem. Soc. Jpn. 2008, 81, 1393; b) Y. Kuninobu, T. Matsuki, K. Takai, J. Am. Chem. Soc. 2009, 131, 9914; c) K. Tsuchikama, M. Kasagawa, Y. K. Hashimoto, K. Endo, T. Shibata, J. Organomet. Chem. 2008, 693, 3939; d) S. Pan, N. Ryu, T. Shibata, J. Am. Chem. Soc. 2012, 134, 17474. W. A. Herrmann, M. Prinz in Applied Homogeneous Catalysis with Organometallic Compounds, Vol. 3, 2nd ed. (Eds.: B. Cornils, W. A. Herrmann), Wiley-VCH, Weinheim, Germany, 2002, p. 1119. K. L. Tan, R. G. Bergman, J. A. Ellman, J. Am. Chem. Soc. 2001, 123, 2685. D. E. Fogg, E. N. dos Santos, Coord. Chem. Rev. 2004, 248, 2365. During preparation of this manuscript, Ong and co-workers reported the nickel-catalyzed addition of azoles to allylbenzene derivatives to afford 1,1-diarylpropanes in a regioselective manner: W.-C. Lee, C.-H. Wang, Y.-H. Lin, W.-C. Shih, T.-G. Ong, Org. Lett. 2013, 15, 5358. For recent examples of C2-alkylation of indole, see refs. 4 d, 4 f, 5 d, and the following: a) L. Jiao, T. Bach, J. Am. Chem. Soc. 2011, 133, 12990; b) L. Jiao, E. Herdtweck, T. Bach, J. Am. Chem. Soc. 2012, 134, 14563; c) Y. Nakao, N. Kashihara, K. S. Kanyiva, T. Hiyama, Angew. Chem. Int. Ed. 2010, 49, 4451; Angew. Chem. 2010, 122, 4553; d) Z. Shi, M. Boultadakis-Arapinis, F. Glorius, Chem. Commun. 2013, 49, 6489; e) B. Punji, W. Song, G. A. Shevchenko, L. Ackermann, Chem. Eur. J. 2013, 19, 10605. The CoBr2–phenanthroline–tBuCH2MgBr system that we reported previously (ref. 4 c) did not promote the reaction at all. T. Kobayashi, H. Yorimitsu, K. Oshima, Chem. Asian J. 2009, 4, 1078. The unreacted alkene was recovered as a mixture of (E)- and (Z)isomers of 1-(but-1-en-1-yl)-4-methoxybenzene and 1-(but-2-en-1yl)-4-methoxybenzene, and hence 1H NMR spectroscopic analysis of their deuterium content was practically difficult. a) Z. Mo, D. Chen, X. Leng, L. Deng, Organometallics 2012, 31, 7040; b) J. A. Przyojski, H. D. Arman, Z. J. Tonzetich, Organometallics 2013, 32, 723; c) Z. Mo, Y. Liu, L. Deng, Angew. Chem. Int. Ed. 2013, 52, 10845; Angew. Chem. 2013, 125, 11045. R. H. Crabtree, The Organometallic Chemistry of The Transition Metals, 5th ed., Wiley, Hoboken, NJ, 2009, p. 229. a) Q. Chen, L. Ilies, E. Nakamura, J. Am. Chem. Soc. 2011, 133, 428; b) W. Song, L. Ackermann, Angew. Chem. Int. Ed. 2012, 51, 8251; Angew. Chem. 2012, 124, 8376; c) T. Yamakawa, N. Yoshikai, Org. Lett. 2013, 15, 196; d) T. Yamakawa, N. Yoshikai, Tetrahedron 2013, 69, 4459. Under the present catalytic system, aryl and heteroaryl imines other than the indole substrates were either not reactive or poorly reactive. For example, aldimine derived from 3-thiophenecarboxaldehyde reacted with cis-b-methylstyrene to afford the desired 1,1-diarylpropane in 7 % yield. Received: January 29, 2014 Published online: March 11, 2014


 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Alkene isomerization-hydroarylation tandem catalysis: indole C2-alkylation with aryl-substituted alkenes leading to 1,1-diarylalkanes.

A cobalt-N-heterocyclic carbene catalyst generated from CoBr2 , imidazolium salt, and cyclohexylmagnesium bromide was found to promote the imine-direc...
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A metal-free and cost-effective synthesis protocol has been initially proposed for the construction of CF3-containing oxindoles via the direct oxidative trifluoromethylation of activated alkenes with Langlois' reagent (CF3SO2Na). The present methodol