Transition-Metal-Catalyzed Ketone α-Alkylation and Alkenylation with Simple Alkenes and Alkynes through a Dual Activation Strategy

Abstract

In this personal account, we summarize our investigations on the α-alkylation and α-alkenylation reactions of ketones with nonactivated alkenes and alkynes, respectively. The serendipitous discovery of C–H alkylation/alkenylation of cyclic 1,2-diketones provided a proof of concept for a dual activation strategy. Extension to the α-alkylation and α-alkenylation of regular ketones was achieved by using 7-azaindoline as a bifunctional ligand. Subsequently, intramolecular coupling ­between ketones and olefins was achieved with Rh- and Ru-based systems, respectively. Finally, branched-selective α-alkylation was achieved through an Ir-catalyzed enamide-mediated C–H alkylation.

1 Introduction

2 Serendipitous Discovery of α-Alkylation and α-Alkenylation of 1,2-Diketones through Enamine-Mediated C–H Activation

3 Intermolecular Ketone α-Alkylation of Regular Ketones with Nonactivated Olefins

4 Intermolecular Ketone α-Alkenylation of Regular Ketones with Nonactivated Alkynes

5 Intramolecular Ketone α-Alkylation of Regular Ketones with Nonactivated Olefins

6 Branched-Selective α-Alkylation of Regular Ketones with Non­activated Olefins

7 Conclusions and Outlook

Key words

ketones - alkylation - alkenylation - directing groups - bifunctional catalysis - C-H activation

• References

• 1a Smith MB, March J. March’s Advanced Organic Chemistry: Reactions, Mechanisms and Structure . Wiley; New York: 2001. 5th ed.
• 1b Carey FA, Sundberg RJ. Advanced Organic Chemistry. Part B: Reactions and Synthesis . Springer; New York: 2007. 5th ed.
• 2a Ono Y. Pure Appl. Chem. 1996; 68: 367
• 2b Anastas PT, Warner JC. Green Chemistry: Theory and Practice . Oxford University Press; Oxford: 1998
• 3a Stork G, Terrell R, Szmuszkovicz J. J. Am. Chem. Soc. 1954; 76: 2029
• 3b Stork G, Landesman H. J. Am. Chem. Soc. 1956; 78: 5128
• 4 Hydrofunctionalization . Ananikov VP, Tanaka M. Springer; Berlin: 2013
• 5 Hack D, Blümel M, Chauhan P, Philipps AR, Ender D. Chem. Soc. Rev. 2015; 44: 6059

For reactions between a ketone and an alkyne, see:
• 6a Binder JT, Crone B, Haug TT, Menz H, Kirsch SF. Org. Lett. 2008; 10: 1025
• 6b Yang T, Ferrali A, Campbell L, Dixon DJ. Chem. Commun. 2008; 2923
• 6c Davies PW, Detty-Mambo C. Org. Biomol. Chem. 2010; 8: 2918
• 6d Boominathan SS. K, Hu W.-P, Senadi GC, Wang J.-J. Adv. Synth. Catal. 2013; 355: 3570

For intramolecular ketone α-alkylations with simple alkenes, see:
• 6e Wang S, Pei T, Han X, Widenhoefer RA. Org. Lett. 2003; 5: 2699
• 6f Xiao Y.-P, Liu X.-Y, Che C.-M. Angew. Chem. Int. Ed. 2011; 50: 4937
• 7 Majima S, Shimizu Y, Kanai M. Tetrahedron Lett. 2012; 53: 4381
• 8 Iwahama T, Sakaguchi S, Ishii Y. Chem. Commun. 2000; 2317
• 9 Huang Z, Lim HN, Young MC, Dong G. Chem. Soc. Rev. 2015; 44: 7764
• 10 Xu T, Alpay D, Guangbin D. Top. Curr. Chem. 2014; 346: 233
• 11 Rulev AYu. New J. Chem. 2017; 41: 4262

For reviews, see:
• 12a Jun C.-H. Chem. Soc. Rev. 2004; 33: 610
• 12b Jun C.-H, Park J.-W. Top. Organomet. Chem. 2007; 24: 117
• 12c Park YJ, Park J.-W, Jun C.-H. Acc. Chem. Res. 2008; 41: 222
• 12d Kim D.-S, Park W.-J, Jun C.-H. Chem. Rev. 2017; 117: 8977

For research articles, see:
• 12e Jun C.-H, Lee H. J. Am. Chem. Soc. 1999; 121: 880
• 12f Jun C.-H, Lee H, Park J.-B, Lee D.-Y. Org. Lett. 1999; 1: 2161
• 12g Jun C.-H, Lee H, Lim S.-G. J. Am. Chem. Soc. 2001; 123: 751
• 12h Park YJ, Kwon B.-I, Ahn J.-A, Lee H, Jun C.-H. J. Am. Chem. Soc. 2004; 126: 13892
• 13a Ponaras AA. J. Org. Chem. 1983; 48: 3866
• 13b Trost BM, Schroeder GM. J. Am. Chem. Soc. 2000; 122: 3785
• 14a Zhang F, Spring DR. Chem. Soc. Rev. 2014; 43: 6906
• 14b Zhao Q, Poisson T, Xavier P, Tatiana B. Synthesis 2017; 49: 4808
• 14c Gandeepan P, Ackermann L. Chem 2018; 4: 199
• 14d St John-Campbell S, Bull JA. Org. Biomol. Chem. 2018; 16: 4582
• 14e Bhattacharya T, Pimparkar S, Maiti D. RSC Adv. 2018; 8: 19456
• 15a Lewis JC, Bergman RG, Ellman JA. Acc. Chem. Res. 2008; 41: 1013
• 15b Colby DA, Bergman RG, Ellman JA. Chem. Rev. 2010; 110: 624
• 15c Dong Z, Ren Z, Thompson SJ, Xu Y, Dong G. Chem. Rev. 2017; 117: 9333
• 16 Wang Z, Reinus BJ, Dong G. J. Am. Chem. Soc. 2012; 134: 13954
• 17a Chun YS, Ko YO, Shin H, Lee S.-g. Org. Lett. 2009; 11: 3414
• 17b Fujimoto T, Endo K, Tsuji H, Nakamura M, Nakamura E. J. Am. Chem. Soc. 2008; 130: 4492
• 17c Yu Y.-Y, Niphakis MJ, Georg GI. Org. Lett. 2011; 13: 5932
• 18a Besset T, Kuhl N, Patureau FW, Glorius F. Chem. Eur. J. 2011; 17: 7167
• 18b Du J, Zhou B, Yang Y, Li Y. Chem. Asian J. 2013; 8: 1386
• 19 Nishimura T, Washitake Y, Uemura S. Adv. Synth. Catal. 2007; 349: 2563
• 20 Wang Z, Reinus BJ, Dong G. Chem. Commun. 2014; 50: 5230
• 21 Fanyang M, Dong G. Science 2014; 345: 68
• 22a Yamaguchi M, Hayashi A, Hirama M. J. Am. Chem. Soc. 1993; 115: 3362
• 22b Yamaguchi M, Sehata M, Hayashi A, Hirama M. J. Chem. Soc., Chem. Commun. 1993; 1708
• 22c Hayashi Y, Yamaguchi M, Hirama M. Synlett 1995; 51
• 22d Yamaguchi M, Tsukagoshi T, Arisawa M. J. Am. Chem. Soc. 1999; 121: 4074
• 23a Trofimov BA, Schmidt EY, Ushakov IA, Zorina NV, Skital’tseva EV, Protsuk NI, Mikhaleva AI. Chem. Eur. J. 2010; 16: 8516
• 23b Trofimov BA, Schmidt EYu, Zorina NV, Ivanova EV, Ushakov IA. J. Org. Chem. 2012; 77: 6880
• 24 Mague JT, Wilkinson G. J. Chem. Soc. A 1966; 1736
• 25 Mo F, Lim HN, Dong G. J. Am. Chem. Soc. 2015; 137: 15518

For Au^I catalysis, see:
• 26a Kennedy-Smith JJ, Staben ST, Toste FD. J. Am. Chem. Soc. 2004; 126: 4526
• 26b Staben ST, Kennedy-Smith JJ, Toste FD. Angew. Chem. Int. Ed. 2004; 43: 5350
• 26c Ochida A, Ito H, Sawamura M. J. Am. Chem. Soc. 2006; 128: 16486
• 26d Pan J.-H, Yang M, Gao Q, Zhu N.-Y, Yang D. Synthesis 2007; 2539
• 26e Ito H, Makida Y, Ohmiya M, Sawamura M. Org. Lett. 2008; 10: 5051

[Re^I catalysis]:
• 26f Kuninobu Y, Kawata A, Takai K. Org. Lett. 2005; 7: 4823

[Ni^II catalysis]:
• 26g Gao Q, Zheng B.-F, Li J.-H, Yang D. Org. Lett. 2005; 7: 2185

[Cu^I catalysis]:
• 26h Bouyssi D, Monteiro N, Balme G. Tetrahedron Lett. 1999; 40: 1297
• 26i Montel S, Bouyssi D, Balme G. Adv. Synth. Catal. 2010; 352: 2315

[Cu^II/Ag^I catalysis]:
• 26j Deng C.-L, Song R.-J, Guo S.-M, Wang Z.-Q, Li J.-H. Org. Lett. 2007; 9: 5111
• 26k Deng C.-L, Zou T, Wang Z.-Q, Song R.-J, Li J.-H. J. Org. Chem. 2009; 74: 412

[In^III catalysis]
• 26l Itoh Y, Tsuji H, Yamagata K.-i, Endo K, Tanaka I, Nakamura M, Nakamura E. J. Am. Chem. Soc. 2008; 130: 17161
• 26m Takahashi K, Midori M, Kawano K, Ishihara J, Hatakeyama S. Angew. Chem. Int. Ed. 2008; 47: 6244

[Fe^III catalysis]
• 26n Chan LY, Kim S, Park Y, Lee PH. J. Org. Chem. 2012; 77: 5239

[Zn^II catalysis]:
• 26o Lebold TP, Leduc AB, Kerr MA. Org. Lett. 2009; 11: 3770
• 26p Leduc AB, Lebold TP, Kerr MA. J. Org. Chem. 2009; 74: 8414
• 26q Deng C.-L, Song R.-J, Liu Y.-L, Li J.-H. Adv. Synth. Catal. 2009; 351: 3096
• 26r Liu Y, Song R.-J, Li J.-H. Synthesis 2010; 3663
• 26s Hess W, Burton JW. Adv. Synth. Catal. 2011; 353: 2966

[Mo⁰ catalysis]
• 26t McDonald FE, Olson TC. Tetrahedron Lett. 1997; 38: 7691

For asymmetric Conia-ene transformations, see:
• 27a Corkey BK, Toste FD. J. Am. Chem. Soc. 2005; 127: 17168
• 27b Yang T, Ferrali A, Sladojevich F, Campbell L, Dixon DJ. J. Am. Chem. Soc. 2009; 131: 9140
• 27c Matsuzawa A, Mashiko T, Kumagai N, Shibasaki M. Angew. Chem. Int. Ed. 2011; 50: 7616
• 27d Sladojevich F, Fuentes de Arriba ÁL, Ortin I, Yang T, Ferrali A, Paton R, Dixon DJ. Chem. Eur. J. 2013; 19: 14286

For Conia-ene reactions between a 1,3-dicarbonyl compound and an alkene, see:
• 28a Pei T, Widenhoefer RA. J. Am. Chem. Soc. 2001; 123: 11290
• 28b Yao X, Li C.-J. J. Am. Chem. Soc. 2004; 126: 6884
• 28c Yao X, Li C.-J. J. Org. Chem. 2005; 70: 5752
• 28d Zhou C.-Y, Che C.-M. J. Am. Chem. Soc. 2007; 129: 5828
• 28e Rueping M, Nachtsheim B, Kuenkel A. Synlett 2007; 1391
• 28f Guérinot A, Fang W, Sircoglou M, Bour C, Bezzenine-Lafollée S, Gandon V. Angew. Chem. Int. Ed. 2013; 52: 5848
• 28g Fang W, Presset M, Guérinot A, Bour C, Bezzenine-Lafollée S, Gandon V. Chem. Eur. J. 2014; 20: 5439
• 29a Arockiam PB, Bruneau C, Dixneuf PH. Chem. Rev. 2012; 112: 5879
• 29b Li B, Dixneuf PH. Top. Organomet. Chem. 2015; 48: 119
• 30 Lim HN, Dong G. Angew. Chem. Int. Ed. 2015; 54: 15294
• 31 Perlmutter P. Conjugate Addition Reactions in Organic Synthesis . Pergamon; Oxford: 1992
• 32a Stork G, Dowd SR. J. Am. Chem. Soc. 1963; 85: 2178
• 32b Corey EJ, Enders D. Tetrahedron Lett. 1976; 17: 3

For selected review and examples of Ir(I)-catalyzed branched-selective hydroarylations of alkenes, see:
• 33a Crisenza GE. M, Bower JF. Chem. Lett. 2016; 45: 2
• 33b Tsuchikama K, Kasagawa M, Hashimoto Y.-K, Endo K, Shibata T. J. Organomet. Chem. 2008; 693: 3939
• 33c Pan S, Ryu N, Shibata T. J. Am. Chem. Soc. 2012; 134: 17474
• 33d Sevov CS, Hartwig JF. J. Am. Chem. Soc. 2013; 135: 2116
• 33e Sevov CS, Hartwig JF. J. Am. Chem. Soc. 2014; 136: 10625
• 33f Crisenza GE, McCreanor NG, Bower JF. J. Am. Chem. Soc. 2014; 136: 10258
• 33g Crisenza GE, Sokolova OO, Bower JF. Angew. Chem. Int. Ed. 2015; 54: 14866
• 33h Shirai T, Yamamoto Y. Angew. Chem. Int. Ed. 2015; 54: 9894
• 33i Ebe Y, Nishimura T. J. Am. Chem. Soc. 2015; 137: 5899
• 33j Hatano M, Ebe Y, Nishimura T, Yorimitsu H. J. Am. Chem. Soc. 2016; 138: 4010
• 33k Grélaud S, Cooper P, Feron LJ, Bower JF. J. Am. Chem. Soc. 2018; 140: 9351

For selected branched-selective hydroarylation of alkenes with other metal catalysis, see [for Ru]:
• 34a Uchimaru Y. Chem. Commun. 1999; 1133

[Ni]:
• 34b Nakao Y, Kashihara N, Kanyiva KS, Hiyama T. J. Am. Chem. Soc. 2008; 130: 16170
• 34c Mukai T, Hirano K, Satoh T, Miura M. J. Org. Chem. 2009; 74: 6410
• 34d Shih W.-C, Chen W.-C, Lai Y.-C, Yu M.-S, Ho J.-J, Yap GP. A, Ong T.-G. Org. Lett. 2012; 14: 2046

[Co]:
• 34e Gao K, Yoshikai N. J. Am. Chem. Soc. 2011; 133: 400
• 34f Lee PS, Yoshikai N. Angew. Chem. Int. Ed. 2013; 52: 1240
• 34g Zell D, Bursch M, Müller V, Grimme S, Ackermann L. Angew. Chem. Int. Ed. 2017; 56: 10378

[Zr]:
• 34h Jordan RF, Taylor DF. J. Am. Chem. Soc. 1989; 111: 778

[Sc]:
• 34i Song GO W. W. N, Hou Z. J. Am. Chem. Soc. 2014; 136: 12209

[Re]:
• 34j Kuninobu Y, Matsuki T, Takai K. J. Am. Chem. Soc. 2009; 131: 9914

For selected examples of activation of alkenyl C−H bonds of enamides through a CMD pathway, see:
• 35a Zhou H, Xu Y.-H, Chung W.-J, Loh T.-P. Angew. Chem. Int. Ed. 2009; 48: 5355
• 35b Zhou H, Chung W.-J, Xu Y.-H, Loh T.-P. Chem. Commun. 2009; 3472
• 35c Stuart DR, Alsabeh P, Kuhn M, Fagnou K. J. Am. Chem. Soc. 2010; 132: 18326
• 35d Rakshit S, Patureau FW, Glorius F. J. Am. Chem. Soc. 2010; 132: 9585
• 35e Hesp KD, Bergman RG, Ellman JA. J. Am. Chem. Soc. 2011; 133: 11430
• 35f Pankajakshan S, Xu Y.-H, Cheng JK, Low MT, Loh T.-P. Angew. Chem. Int. Ed. 2012; 51: 5701
• 35g Li B, Wang N, Liang Y, Xu S, Wang B. Org. Lett. 2013; 15: 136
• 35h Wang L, Ackermann L. Org. Lett. 2013; 15: 176
• 35i Zhao M.-N, Ren Z.-H, Wang Y.-Y, Guan Z.-H. Org. Lett. 2014; 16: 608
• 35j Wu J, Xu W, Yu Z.-X, Wang J. J. Am. Chem. Soc. 2015; 137: 9489
• 36 Xing D, Dong G. J. Am. Chem. Soc. 2017; 139: 13664
• 37 Huang G, Liu P. ACS Catal. 2016; 6: 809
• 38 Li X, Wu H, Lang Y, Huang G. Catal. Sci. Technol. 2018; 8: 2417