Rhodium(I)-Catalyzed Benzannulation of Heteroaryl Propargylic Esters: Synthesis of Indoles and Related Heterocycles.

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Chemistry. Author manuscript; available in PMC 2017 July 18. Published in final edited form as: Chemistry. 2016 July 18; 22(30): 10410–10414. doi:10.1002/chem.201602088.

Rhodium(I)-Catalyzed Benzannulation of Heteroaryl Propargylic Esters: Synthesis of Indoles and Related Heterocycles** Dr. Xiaoxun Li[a], Dr. Haibo Xie[a], Xiaoning Fu[b], Ji-tian Liu[a], Hao-yuan Wang[a], Prof. Dr. Bao-min Xi[c], Prof. Dr. Peng Liu[d], Prof. Dr. Xiufang Xu[b], and Prof. Dr. Weiping Tang[a],[e] Bao-min Xi: [email protected]; Peng Liu: [email protected]; Xiufang Xu: [email protected]; Weiping Tang: [email protected]

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[a]School

of Pharmacy, University of Wisconsin-Madison, Madison, WI 53705, USA

[b]Department

of Chemistry, Key Laboratory of Advanced Energy Materials Chemistry (Ministry of Education), Nankai University, Tianjin, 300071, P. R. China [c]Guangdong

Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Gaungzhou, Guangdong, 510515, P. R. China

[d]Department

of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA

[e]Department

of Chemistry, University of Wisconsin-Madison, Madison, WI 53706

Abstract Author Manuscript

A de novo synthesis of benzene ring allows the preparation of a diverse range of heterocycles including indoles, benzofurans, benzothiophenes, carbazoles and dibenzofurans from simple heteroaryl propargylic esters using a unified carbonylative benzannulation strategy. Multiple substituents can now be easily introduced to the C4–C7 positions of indoles and related heterocycles.

Graphical Abstract A unified strategy was developed for the synthesis of indoles and related heterocycles from simple heteroaryl propargylic esters and various substituents could be introduced to C4–C7 positions of indoles and the benzene portion of other related heterocycles.

Author Manuscript Correspondence to: Bao-min Xi, [email protected]; Peng Liu, [email protected]; Xiufang Xu, [email protected]; Weiping Tang, [email protected]. Dedicated to Professor Stuart L. Schreiber on the occasion of his 60th birthday. Supporting information for this article is given via a link at the end of the document.

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Keywords annulation; rhodium; catalysis; indole; carbonylation

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The importance of indole as one of the most abundant heterocycles in natural products and pharmaceutical agents continues to inspire the development of general methods for their preparation.[1] The majority of indole syntheses focused on the formation of pyrroles from substituted benzene derivatives by forming bonds a–d or their combinations via cyclization or cycloaddition reactions (X = NR, Scheme 1). Substituents on the C4–C7 positions of indoles need to be derived from polysubstituted benzene derivatives, which are often not readily available. Synthesis of indoles from substituted pyrroles by forming bonds e–i would be different from most methods in the literature and allows the introduction substituents to the C4–C7 positions on indoles from the corresponding reactants. This approach, however, is challenging as it requires a de novo synthesis of the benzenoid ring.[2] We herein report a carbonylative benzannulation strategy for the synthesis of highly substituted indoles 3 and 4 from pyrrolyl propargylic esters 1 and 2, respectively. Multiple substituents on C4–C7 positions of the indole products can be easily introduced from the corresponding propargylic esters via the de novo synthesis of the benzenoid ring.[2] We also demonstrated that the dearomative benzannulation strategy could be extended to the synthesis of other heterocycles such as benzofurans, benzothiophenes, carbazoles and dibenzofurans.

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Among the benzannulation methods, Dötz benzannulation[3] of alkenyl Fischer carbene with alkyne proved to be extremely versatile for the synthesis of phenols with a para-alkoxy group.[4] Wulff and Merlic developed a complimentary benzannulation of dienyl Fischer carbenes for the synthesis of phenols with an ortho-alkoxy group.[5] Barluenga extended the benzannulation strategy to the synthesis of benzofurans from alkynyl Fischer carbene and furfural derivatives.[6] Very recently, Katukojvala reported a [4+2] benzannulation of pyrroles with enalcarbenoid derived from diazo compounds for the synthesis of indoles.[7]

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Compared to Fischer carbenes[4] and diazo compounds,[8] propargylic esters are more desirable starting materials as precursors of metal carbenes through a 1,2-acyloxy migration process.[9] We[10] and others[11] have demonstrated that vinyl propargylic esters (i.e. 3acyloxy-1,4-enynes) can be employed as a five-carbon building block in [5+1] cycloadditions through carbene intermediates for the synthesis of resorcinols. We also showed that the same 1,4-enyne five-carbon building block could be employed in [5+2] cycloadditions with alkynes or alkenes through carbene intermediates for the synthesis of 7membered rings.[12] We envisioned that a variety of highly substituted heterocycles might be prepared if propargylic esters 1 or 2 could undergo benzannulation with carbon monoxide through the same metal carbene intermediate. However, the feasibility of this transformation is not obvious before we initiate our investigation because a dearomatization event is required for the formation of indoles 3 or 4 from 1 or 2, respectively,[13] while all previous studies involve 1,4-enyne systems.[10–12]

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Propargylic ester 1a (Table 1) was prepared from the corresponding aldehyde in a one-pot procedure and 83% yield. Treatment of this ester with strong π-acidic metals that are capable of promoting 1,2-acyloxy migration of propargylic esters[9] did not yield any desired product (entries 1 and 2). We were pleased to find that a 83% yield was observed for indole 3a when [Rh(CO)2Cl]2 was employed as the catalyst (entry 3). Most rhodium catalysts could promote the benzannulation reaction at room temperature (entries 4–6) with the exception of Wilkinson’s catalyst (entry 7). High yields were observed in most solvents (entries 8–12) and the yield was slightly better in DCM (entry 10). The catalyst loading could be lowered down to 3 mol%, while the reaction was still worked at room temperature (entry 13).

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We then set out to examine the scope of this new benzannulation for the synthesis of highly substituted indoles (Table 2). The type of esters did not impact the reaction much (entries 1– 3). The tosyl group could also be replaced by p-nitrobenzenesulfonyl or Boc- groups (entries 4–6), though slightly higher temperature was required in the latter case. The reaction could tolerate various functional groups, including bromine, ketone, free alcohol, and ester (entries 7–10). It is worth to point out that substituents on the 4-position of the pyrrole did not interfere with annulations that occurred on the adjacent 3-position. A carboxylic ester could be introduced to the C5-position of the indole by starting with the corresponding ynoate substrate (entry 11). Substrate 1l with a methyl group did not yield any desired indole product (entry 12), which is consistent with the preferred 1,3-acyloxy migration mode for propargylic esters bearing an internal alkyne.[9]

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We next turned out attention to substrates with a propargylic ester on the 3-position of the pyrrole. Slightly lower yields were obtained for pyrrolyl propargylic esters with either a Ntosyl or N-Boc group (entries 13 and 14). Cationic rhodium catalyst gave the best yield in the latter case. The reaction also worked with substrates bearing a tertiary ester (entry 15). An additional methyl group was introduced to the C4-position of the indole in this case. The Boc-protecting group in products 3f and 4b can be easily removed to yield the corresponding free indoles.[14]

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A unified strategy may be realized for various indole-related heterocycles by simply replacing the pyrrole ring with other heteroaryl groups (Table 3). Indeed, benzofurans and benzothiophenes with multiple substituents on the C4–C7 positions were prepared in good yields from the corresponding aryl propargylic esters (entries 1–4). It is worth to mention that substrates 5a and 5b were prepared from bio-renewable feedstock furfural in high yields.[15] Tricyclic carbazoles 6e and 6f were easily prepared from the corresponding 2indolyl propargylic ester 5e and 3-indolyl propargylic ester 5f, respectively (entries 5 and 6). These two carbazoles have complementary substituents on the newly formed benzene ring. Tricyclic dibenzofuran 6g was synthesized from the corresponding aryl propargylic ester 5g (entry 7). Multiple substituents could be introduced to the indolyl propargylic ester starting materials and highly substituted carbazoles on both benzene rings were prepared efficiently (entries 8–11). No benzannulation product was observed for phenyl propargylic ester 5l (entry 12). Instead, carboxylic acid 7 was obtained in 52% yield. We also tried to replace the phenyl group in 5l by p-methoxyphenyl group and no desired benzannulation product was


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observed. A 36% yield of product 6m could be obtained from nathphyl propargylic ester 5m. The pivalate and hydroxyl groups derived from the benzannulation can serve as handles for the introduction of more functional groups. For example, the former may undergo direct Nicatalyzed cross-coupling reactions;[16] and the latter can be converted to triflate for Pdcatalyzed cross-coupling reactions. As shown in Scheme 2, a Pd-catalyzed reduction afforded indole product 8; and a Sonogashira coupling with a terminal alkyne yielded indole product 9. An allyl substituent could be introduced to the C5- or C6-position of indoles 10 and 11, respectively, by a sequence of allylation of the phenolic OH group followed by Claisen-rearrangement. The Ts-group in product 6k can be easily removed to afford carbazole 12 while retaining the pivalate group.

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In Rh-catalyzed cycloadditions involving 3-acyloxy-1,4-enynes, the 1,2-migration of ester was the rate-determining step and the reaction was significantly faster for esters bearing an electron-donating group.[10, 12d, 17] Under our standard conditions, both products 6n and 6o could be prepared in 70% and 66% yields, respectively. Surprisingly, we found that the benzannulation of 5n with an electron-rich ester was completed in less than 1 min at room temperature. We then mixed substrates 5n and 5o in a 1:1 ratio and tried to examine the rate difference between them. After running the reaction for just around 10 s, we observed over 95% yield of 6n and less than 5% yield of 6o based on 1H NMR using CH2Br2 as the internal standard. The first 1,2-acyloxy migration step is likely the rate-determining step for the benzannulation of heteroaryl propargylic esters.

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Previously, a concerted 1,2-acyloxy migration oxidative cyclization was proposed as the initial step for Rh-catalyzed cycloadditions of 3-acyloxy-1,4-enyne 13 to form metallacycle 14 and metal carbene intermediate 14′ (Scheme 4).[17a] The double bond in the aryl group of 15, however, is unlikely to coordinate to rhodium. A sequence of 1,2-acyloxy migration, carbene formation, and CO insertion may afford ketene 18. A dearomatic 6πelectrocyclization of ketene 18 followed by aromatization may yield product 19. Although metal catalysts (e.g. Au- or Pt-based complexes) can promote the 1,2-acyloxy migration of propargylic esters to generate metal-carbene intermediates, very few of them have the ability to undergo CO insertion to yield ketenes.[9] This may explain why only Rh(I)-complexes worked for the carbonylative benzannulation of aryl propargylic esters among the π-acidic metals in Table 1.

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To further understand the details of the mechanism, we performed Density Functional Theory (DFT) calculations for several potential pathways. The preferred one is shown in Scheme 5 and other pathways are outlined in the Supporting Information. DFT calculations indicate that [Rh(CO)3Cl] is the resting state of the catalyst (Scheme 5). Substrate 5b undergoes ligand exchange with [Rh(CO)3Cl] to form complex 20. This 16-electron rhodium complex adopts a square-planar geometry, where only the alkyne coordinates to the Rh centre. This is different from the Rh(I)-catalyzed [5+n] cycloaddition of 3-acyloxy-1,4enyne with alkyne and CO, where the rhodium binds to both alkyne and alkene simultaneously in the initial π-complex.[17] Promoted by the Rh(I) catalyst, the 1,2-acyloxy migration occurs stepwise with an overall barrier of 21.9 kcal/mol, leading to the formation


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of zwitterion intermediate 22, where the positive charge is stabilized by both the alkene and the furan moieties. The 1,2-acyloxy migration requires the highest free energy of activation (TS1), thus being rate determining step, which is consistent with faster reactions for electron-rich esters such as 5n.[17]

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Intermediate 22 can be isomerized a four-membered metallacycle, which can undergo CO insertion and subsequent reductive elimination to afford ketene intermediate similar to 18 for 6π-electrocyclization and aromatization to furnish benzofuran product 6b, as shown in the Supporting Information (Figure S1). In contrast to reactions involving 3-acyloxy-1,4-enynes, where the 1,4-enyne serves as a bidentate ligand,[17] the furan ring does not coordinate to rhodium at any time. The benzannulation involves much higher energy barriers when the furan moiety coordinates to the metal centre to form metallacyles related to 14 or 14′ as shown in Figures S1 and S2). It is clear that aryl propargylic esters behave very differently from 1,4-enynes we studied before. In summary, we have developed a practical and unified method for the synthesis of indoles and related heterocycles. This method differs from most previous approaches by allowing the introduction of various substituents to the benzene-portion of indoles and related heterocycles. We demonstrated that indoles and related heterocycles with substituents at any of C4–C7 positions could be prepared by starting with appropriately substituted heteroaryl propargylic esters. We anticipate that this method will find immediate applications in many areas of organic, medicinal and material chemistry. Computational studies suggest that a zwitterion intermediate instead of a metallacycle intermediate is formed after the 1,2acyloxy migration. This finding may have broad implications in many transition metalcatalyzed reactions.

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Supplementary Material Refer to Web version on PubMed Central for supplementary material.

Acknowledgments We thank NIH (R01GM088285), NSF (CHE-1464754) and University of Wisconsin-Madison for financial support. X. Xu thanks Tianjin Natural Science Foundation (No. 21421001 X.X.), and MOE Innovation Teams (Nos. IRT-13R30 and IRT13022) of China for funding. J.-t. Liu thanks Chinese Scholarship Council for financial support. B.-m. Xi thanks Southern Medical University for financial support of the visiting professorship at UW-Madison. This study made use of the Medicinal Chemistry Center at UW-Madison instrumentation, funded by the Wisconsin Alumni Research Foundation (WARF) and the UW School of Pharmacy.

References Author Manuscript

1. For selected reviews on indole synthesis, see: Barluenga J, Rodriguez F, Fananas FJ. Chem Asian J. 2009; 4:1036. [PubMed: 19360759] Taber DF, Tirunahari PK. Tetrahedron. 2011; 67:7195. [PubMed: 25484459] Vicente R. Org Biomol Chem. 2011; 9:6469. [PubMed: 21779596] Platon M, Amardeil R, Djakovitch L, Hierso JC. Chem Soc Rev. 2012; 41:3929. [PubMed: 22447100] 2. For a leading reference on de novo synthesis of polysubstituted benzenes, see: Izawa Y, Pun D, Stahl SS. Science. 2011; 333:209. [PubMed: 21659567] For a recent example on making indoles by benzannulation, see: Lam TY, Wang Y-P, Danheiser RL. J Org Chem. 2013; 78:9396. [PubMed: 23952525]


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3. Dötz KH. Angew Chem Int Ed. 1975; 14:644.Dötz KH. Angew Chem Int Ed. 1984; 23:587.Wulff WD, Tang PC, Chan KS, McCallum JS, Yang DC, Gilbertson SR. Tetrahedron. 1985; 41:5813. 4. For recent reviews on reactions involving Fischer carbenes, see: Gomez-Gallego M, Mancheno MJ, Sierra MA. Acc Chem Res. 2005; 38:44. [PubMed: 15654736] Dötz KH, Stendel J Jr. Chem Rev. 2009; 109:3227. [PubMed: 19642645] 5. a) Wulf, WD. Advances in Metal-Organic Chemistry. Liebeskind, LS., editor. Vol. 1. JAI Press; Greenwich, CT: 1989. p. 336b) Lian YQ, Wulff WD. J Am Chem Soc. 2005; 127:17162. [PubMed: 16332045] c) Merlic CA, Xu DQ. J Am Chem Soc. 1991; 113:7418.d) Merlic CA, Burns EE, Xu DQ, Chen SY. J Am Chem Soc. 1992; 114:8722. 6. Barluenga J, Gomez A, Santamaria J, Tomas M. J Am Chem Soc. 2009; 131:14628. [PubMed: 19780554] 7. Dawande SG, Kanchupalli V, Kalepu J, Chennamsetti H, Lad BS, Katukojvala S. Angew Chem Int Ed. 2014; 53:4076. 8. For selected reviews, see: Ye T, McKervey MA. Chem Rev. 1994; 94:1091.Doyle MP, McKervey MA, Ye T. Modern Catalytic Methods for Organic Synthesis with Diazo Compounds. John Wiley & SonsNew York1998Zhang Z, Wang J. Tetrahedron. 2008; 64:6577. 9. For selected reviews, see: Marion N, Nolan SP. Angew Chem Int Ed. 2007; 46:2750.MarcoContelles J, Soriano E. Chem Eur J. 2007; 13:1350. [PubMed: 17200921] Shu XZ, Shu D, Schienebeck CM, Tang W. Chem Soc Rev. 2012; 41:7698. [PubMed: 22895533] 10. Schienebeck CM, Song W, Smits AM, Tang W. Synthesis. 2015; 47:1076. [PubMed: 26508806] 11. a) Brancour C, Fukuyama T, Ohta Y, Ryu I, Dhimane AL, Fensterbank L, Malacria M. Chem Commun. 2010; 46:5470.b) Fukuyama T, Ohta Y, Brancour C, Miyagawa K, Ryu I, Dhimane AL, Fensterbank L, Malacria M. Chem Eur J. 2012; 18:7243. [PubMed: 22505021] 12. a) Shu XZ, Huang S, Shu D, Guzei IA, Tang W. Angew Chem Int Ed. 2011; 50:8153.b) Shu XZ, Li X, Shu D, Huang S, Schienebeck CM, Zhou X, Robichaux PJ, Tang W. J Am Chem Soc. 2012; 134:5211. [PubMed: 22364320] c) Shu XZ, Schienebeck CM, Song W, Guzei IA, Tang W. Angew Chem Int Ed. 2013; 52:13601.d) Schienebeck CM, Robichaux PJ, Li X, Chen L, Tang W. Chem Commun. 2013; 49:2616.e) Schienebeck CM, Li X, Shu XZ, Tang W. Pure Appl Chem. 2014; 86:409. [PubMed: 24839310] f) Shu, X-z; Schienebeck, CM.; Li, X.; Zhou, X.; Song, W.; Chen, L.; Guzei, IA.; Tang, W. Org Lett. 2015; 17:5128. [PubMed: 26440751] 13. For selected reviews on dearomatization reactions, see: Pape AR, Kaliappan KP, Kundig EP. Chem Rev. 2000; 100:2917. [PubMed: 11749310] Roche SP, Porco JA Jr. Angew Chem Int Ed. 2011; 50:4068.Zhuo CX, Zhang W, You SL. Angew Chem Int Ed. 2012; 51:12662.Ding Q, Zhou X, Fan R. Org Biomol Chem. 2014; 12:4807. [PubMed: 24875150] Zhuo CX, Zheng C, You SL. Acc Chem Res. 2014; 47:2558. [PubMed: 24940612] 14. Shu D, Winston-McPherson GN, Song W, Tang W. Org Lett. 2013; 15:4162. [PubMed: 23909946] 15. Sheldon RA. Green Chem. 2014; 16:950. 16. Quasdorf KW, Tian X, Garg NK. J Am Chem Soc. 2008; 130:14422. [PubMed: 18839946] 17. a) Xu X, Liu P, Shu XZ, Tang W, Houk KN. J Am Chem Soc. 2013; 135:9271. [PubMed: 23725341] b) Ke X, Schienebeck CM, Zhou C, Xu X, Tang W. Chin Chem Lett. 2015; 26:730. [PubMed: 27152064]

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Scheme 1.

Strategies for the Synthesis of Indoles and Related Heterocycles


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Author Manuscript Author Manuscript Author Manuscript Scheme 2.

Further Functionalization of Indoles Derivatives


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Scheme 3.

Effect of Ester for the Benzannulation Reaction

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Scheme 4.

Proposed Mechanism Based on Previous [5+2] Cycloaddition of 3-Acyloxy-1,4-enynes and Alkynes


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Author Manuscript Author Manuscript Scheme 5.

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Gibbs Free Energy Profiles for 1,2-Acyloxy Migration. Energies Are in kcal/mol and Calculated Using B3LYP/SDD-6-31G(d)/SMD(CH2Cl2)


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Table 1

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Screening of Catalysts and Conditions for substrate 1a

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entry

conditions

yield[a]

1

PtCl2, (5 mol %), DCE, 60 °C, 12h

0

2

AuCl(PPh3) (5 mol %), DCE, 60 °C, 12h

0

3

[Rh(CO)2Cl]2 (5 mol %), DCE, 60 °C, 12h

83%

4

[Rh(CO)2Cl]2 (5 mol %), DCE, rt, 12h

89%

5

[Rh(COD)2Cl]2 (5 mol %), DCE, rt, 12h

79%

6

Rh(COD)2]BF4 (5 mol %), DCE, rt, 12h

58%

7

[Rh(Ph3P)3Cl] (5 mol %), DCE, rt, 12h

0

8

[Rh(CO)2Cl]2 (5 mol %), CHCl3, rt, 12h

84%

9

[Rh(CO)2Cl]2 (5 mol %), TCE, rt, 12

90%

10

[Rh(CO)2Cl]2 (5 mol %), DCM, rt, 12h

92%

11

[Rh(CO)2Cl]2 (5 mol %), toluene, rt, 12h

81%

12

[Rh(CO)2Cl]2 (5 mol %), dioxane, rt, 12h

90%

13


91%

14


38%

[a] Yields were calculated based on 1H NMR using CH2Br2 as the internal standard. DCE = dichloroethane; TCE = tetrachloroethylene;


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Table 2

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Scope of the RhI–Catalysed Benzannulation for Indoles[a]


Entry

substrates

products

yields

1

1a, R = Piv

3a

86%

2

1b, R = Ac

3b

80%

3

1c, R = Bz

3c

88%

4

1d, Ar = p-NO2, R = Piv

3d

86%

5

1e, Ar = p-NO2, R = Ac

3e

81%

6[b]

1f

3f

82%

7

1g, R = Br

3g

84%

8

1h, R = Ac

3h

80%

9

1i, R = OH

3i

82%

10

1j, R = OAc

3j

78%


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Entry

substrates

products

yields

11

1k, R = CO2Et

3k

58%

12

1l, R = Me

3l

0

13

2a, E = Ts, R = H, R′ = Piv

4a

68%

14[c]

2b, E = Boc, R = H, R′ = Piv

4b

65%

15[b]

2c, E = Ts, R = Me, R′ = Ac

4c

62%

[a] Condition A: [Rh(CO)2Cl]2 (3 mol %), CO balloon (1 atm), CH2Cl2, rt, 8–12h unless noted otherwise. All yields are isolated yields. [b]

Condition B: [Rh(CO)2Cl]2 (3 mol %), CO balloon (1 atm), dioxane, 60 °C, 8–12h.

[c] Condition C: [Rh(COD)2]BF4 (5 mol %), CO balloon (1 atm), CH2Cl2, rt, 8–12h.


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Table 3

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Scope of the RhI –Catalysed Benzannulation for Other Heterocycles[a]


entry

substrates

products

yields

1

5a, R = Piv

6a

81%

2

5b, R = Ac

6b

64%

3

5c

6c

88%

4

5d

6d

50%

5

5e

6e

82%

6

5f

6f

58%

7

5g

6g

74%


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entry

substrates

products

yields

8

5h, X = F, Y = Z = H

6h

70%

9

5i, Y = F, X = Z = H

6i

65%

10

5j, Z = F, X = Y = H

6j

55%

11

5k

6k

76%

12

5l

7

52%

13

5m

6m

36%

[a] Condition A: [Rh(CO)2Cl]2 (3–5 mol %), CO balloon (1 atm), CH2Cl2, rt, 8–12h unless noted otherwise. All yields are isolated yields.


Rhodium enalcarbenoids: direct synthesis of indoles by rhodium(II)-catalyzed [4+2] benzannulation of pyrroles.

Palladium-catalyzed synthesis of 2-(aminomethyl)indoles from 3-(o-trifluoroacetamidoaryl)-1-propargylic alcohols and amines.

intramolecular cyclization cascade sequence in water or DMSO.

cyclization of indoles and pyrroles: divergent synthesis of heterocycles.

Copper-catalyzed intermolecular asymmetric propargylic dearomatization of indoles.

Efficient synthesis of eight-membered nitrogen heterocycles from o-propargylic oximes by rhodium-catalyzed cascade reactions.

Synthesis of polysubstituted 1,2-dihydroquinolines and indoles via cascade reactions of arylamines and propargylic alcohols catalyzed by FeCl3·6H2O.

Benzannulation of indoles to carbazoles and its applications for syntheses of carbazole alkaloids.

Gold-Catalyzed Intramolecular Cyclizations of Cyclopropenes with Propargylic Esters.

Rearrangements of propargylic esters can be induced by some electrophiles.

Dearomative [2 + 2] Cycloaddition and Formal C-H Insertion Reaction of o-Carboryne with Indoles: Synthesis of Carborane-Functionalized Heterocycles.

Borylation of propargylic substrates by bimetallic catalysis. Synthesis of allenyl, propargylic, and butadienyl Bpin derivatives.

Catalytic asymmetric synthesis of [2,3]-fused indoline heterocycles through inverse-electron-demand aza-Diels-Alder reaction of indoles with azoalkenes.

Enantioselective synthesis of highly functionalized dihydrofurans through copper-catalyzed asymmetric formal [3+2] cycloaddition of β-ketoesters with propargylic esters.

Synthesis of saturated N-heterocycles.

Propargylic sulfides: synthesis, properties, and application.

Chemistry of bridged lactams and related heterocycles.

Synthesis and anticonvulsant activity of some new pyrazolo[3,4-b]pyrazines and related heterocycles.

One-pot synthesis and applications of N-heteroaryl iodonium salts.

Palladium-Catalyzed Modular Synthesis of Substituted Piperazines and Related Nitrogen Heterocycles.

The synthesis of vinylogous amidine heterocycles.

Diurnal profiles of melatonin synthesis-related indoles, catecholamines and their metabolites in the duck pineal organ.

Copper-catalyzed propargylic substitution of dichloro substrates: enantioselective synthesis of trisubstituted allenes and formation of propargylic quaternary stereogenic centers.

Gold(I)-catalyzed intramolecular cycloisomerization of propargylic esters with furan rings.