N-Alkylsulfonamides as Useful Carbon Electrophiles

Abstract

The cleavage of the sp³ carbon–nitrogen bonds in N-alkylsulfonamides has been utilized for the selective formation of various carbon–carbon and carbon–heteroatom bonds. When N-alkylsulfonamides undergo sp³ carbon–nitrogen bond cleavage in the presence of acid catalysts, the resulting carbocations can react with a broad range of carbon, sulfur, nitrogen, oxygen, or hydride nucleophiles. On the other hand, basic conditions allow N-alkylsulfonamides to act as sp³ carbon electrophiles in reactions with strong nucleophiles. In general, N-benzylic, N-allylic, and N-propargylic sulfonamides serve as suitable substrates, and their reactions with nucleophiles provide ready access to a wide range of functionalized molecules.

1 Introduction

2 Mechanism

3 Reactions with Carbon Nucleophiles

3.1 Active Methylene Compounds

3.2 Ketones and Aldehydes

3.3 Aromatic Compounds

3.4 Alkynes, Alkenes, and Arylallenes

3.5 Silylated Carbon Nucleophiles

3.6 Grignard Reagents

4 Reactions with Sulfur Nucleophiles

4.1 Thiols and Thiophenols

4.2 Thioacetic acid

4.3 Sulfinic Acids

5 Reactions with Nitrogen Nucleophiles

6 Reactions with Oxygen Nucleophiles

7 Reduction

8 Conclusion

Key words

sulfonamides - electrophiles - nucleophiles - carbo­cations - alkylation - heterocycles

• References

• 1 Carey FA, Sundberg RJ. Advanced Organic Chemistry Part B: Reactions and Synthesis . 5th ed. Springer; New York: 2007

Although the sp³ carbon–nitrogen bonds in certain alkylamines can be cleaved by some metals and strong bases, alkylamines have rarely been used in reactions with nucleophiles. For reviews, see:
• 2a Greene TW, Wuts PG. M. Protective Groups in Organic Synthesis . 3rd ed. Wiley; New York: 1999
• 2b Escoubet S, Gastaldi S, Bertrand M. Eur. J. Org. Chem. 2005; 3855

For examples of direct transformation of primary and secondary alkylamines through sp³ carbon–nitrogen bond cleavage, see:
• 3a Trost BM, Keinan E. J. Org. Chem. 1980; 45: 2741
• 3b Kunakova RV, Gaisin RL, Sirazova MM, Dzhemilev UM. Izv. Akad. Nauk SSSR, Ser. Khim. 1983; 32: 157 ; Bull. Acad. Sci. USSR, Div. Chem. Sci. (Engl. Transl.); 1983, 32: 133
• 3c Murahashi S.-I, Makabe Y, Kunita K. J. Org. Chem. 1988; 53: 4489
• 3d Garro-Helion F, Merzouk A, Guibé F. J. Org. Chem. 1993; 58: 6109
• 3e Murahashi S.-I, Imada Y, Nishimura K. Tetrahedron 1994; 50: 453
• 3f Pawlas J, Nakao Y, Kawatsura M, Hartwig JF. J. Am. Chem. Soc. 2002; 124: 3669
• 3g Zhao X, Liu D, Guo H, Liu Y, Zhang W. J. Am. Chem. Soc. 2011; 133: 19354
• 3h Li M.-B, Wang Y, Tian S.-K. Angew. Chem. Int. Ed. 2012; 51: 2968
• 3i Wu X.-S, Chen Y, Li M.-B, Zhou M.-G, Tian S.-K. J. Am. Chem. Soc. 2012; 134: 14694
• 3j Geng W, Zhang W.-X, Hao W, Xi Z. J. Am. Chem. Soc. 2012; 134: 20230
• 4a Chung KH, Kim JN, Ryu EK. Tetrahedron Lett. 1994; 35: 2913
• 4b Seong MR, Lee HJ, Kim JN. Tetrahedron Lett. 1998; 39: 6219
• 4c Lee HJ, Seong MR, Song HN, Kim JN. Bull. Korean Chem. Soc. 1999; 20: 267
• 4d Esquivias J, Gómez-Arrayás R, Carretero JC. Angew. Chem. Int. Ed. 2006; 45: 629
• 5 Olah GA, Krishnamurti R, Surya GK In Comprehensive Organic Synthesis . Vol. 3. Trost BM, Fleming I. Pergamon; Oxford: 1991: 293
• 6 For a detailed procedure, see: Yang B.-L, Tian S.-K. Chem. Commun. 2010; 46: 6180
• 7 Liu C.-R, Li M.-B, Yang C.-F, Tian S.-K. Chem. Eur. J. 2009; 15: 793
• 8 Wu X.-S, Tian S.-K. Chem. Commun. 2012; 48: 898
• 9 Li M.-B, Tang X.-L, Tian S.-K. Adv. Synth. Catal. 2011; 353: 1980

For enhancement of the catalytic activity of metal Lewis acids with silicon Lewis acids in the cleavage of sp³ carbon–halogen and sp³ carbon–oxygen bonds, see:
• 10a Onishi Y, Ito T, Yasuda M, Baba A. Tetrahedron 2002; 58: 8227
• 10b Saito T, Nishimoto Y, Yasuda M, Baba A. J. Org. Chem. 2006; 71: 8516

Before this investigation, we found that a few Lewis acids in combination with TMSCl (a byproduct) were effective in catalyzing imine additions; see:
• 11a Yang B.-L, Tian S.-K. Eur. J. Org. Chem. 2007; 4646
• 11b Song Q.-Y, Yang B.-L, Tian S.-K. J. Org. Chem. 2007; 72: 5407
• 12 For a related example, see: Jiang Z.-Y, Zhang C.-H, Gu F.-L, Yang K.-F, Lai G.-Q, Xu L.-W, Xia C.-G. Synlett 2010; 1251

For reviews, see:
• 13a Keay BA, Dibble PW In Comprehensive Heterocyclic Chemistry II . Vol. 2. Katritzky AR, Rees CW, Scriven EF. V. Pergamon; Oxford: 1996: 395
• 13b Brown RC. D. Angew. Chem. Int. Ed. 2005; 44: 850
• 13c Kirsch SF. Org. Biomol. Chem. 2006; 4: 2076

For recent examples, see:
• 14a Rohr K, Mahrwald R. Org. Lett. 2011; 13: 1878
• 14b Yang C.-F, Shen C, Wang J.-Y, Tian S.-K. Org. Lett. 2012; 14: 3092
• 14c Yang C.-F, Shen C, Li H.-H, Tian S.-K. Chin. Sci. Bull. 2012; 57: 2377
• 14d Zheng Y, Xiong H.-Y, Nie J, Hua M.-Q, Ma J.-A. Chem. Commun. 2012; 48: 4308
• 14e Zhong F, Yao W, Dou X, Lu Y. Org. Lett. 2012; 14: 4018
• 14f Chen Y, Tian S.-K. Chin. J. Chem. 2013; 31: 37
• 15 Yang C.-F, Wang J.-Y, Tian S.-K. Chem. Commun. 2011; 47: 8343
• 16a Shaikh RR, Mazzanti A, Petrini M, Bartoli G, Melchiorre P. Angew. Chem. Int. Ed. 2008; 47: 8707
• 16b Cozzi PG, Benfatti F, Zoli L. Angew. Chem. Int. Ed. 2009; 48: 1313
• 16c Brown AR, Kuo W.-H, Jacobsen EN. J. Am. Chem. Soc. 2010; 132: 9286
• 16d Zhang L, Cui L, Li X, Li J, Luo S, Cheng J.-P. Chem. Eur. J. 2010; 16: 2045
• 16e Zhang L, Cui L, Li X, Li J, Luo S, Cheng J.-P. Eur. J. Org. Chem. 2010; 4876

For reviews of asymmetric enamine catalysis, see:
• 17a Mukherjee S, Yang JW, Hoffmann S, List B. Chem. Rev. 2007; 107: 5471
• 17b Melchiorre P, Marigo M, Carlone A, Bartoli G. Angew. Chem. Int. Ed. 2008; 47: 6138
• 17c Pihko PM, Majander I, Erkkilä A. Top. Curr. Chem. 2010; 291: 29
• 18 Weng Z.-T, Li Y, Tian S.-K. J. Org. Chem. 2011; 76: 8095

For reviews, see:
• 19a Duxbury DF. Chem. Rev. 1993; 93: 381
• 19b Shchepinov MS, Korshun VA. Chem. Soc. Rev. 2003; 32: 170
• 19c Nair V, Thomas S, Mathew SC, Abhilash KG. Tetrahedron 2006; 62: 6731
• 20a Ke B, Qin Y, He Q, Huang Z, Wang F. Tetrahedron Lett. 2005; 46: 1751
• 20b Temelli B, Unaleroglu C. Tetrahedron Lett. 2005; 46: 7941
• 20c Soueidan M, Collin J, Gil R. Tetrahedron Lett. 2006; 47: 5467
• 20d Wang Y.-Q, Song J, Hong R, Li H, Deng L. J. Am. Chem. Soc. 2006; 128: 8156
• 21 Liu C.-R, Li M.-B, Yang C.-F, Tian S.-K. Chem. Commun. 2008; 1249
• 22 Tian Y, Sui Y, Gu Y, Tian S.-K. Adv. Synth. Catal. 2012; 354: 3475
• 23 Liu C.-R, Yang F.-L, Jin Y.-Z, Ma X.-T, Cheng D.-J, Li N, Tian S.-K. Org. Lett. 2010; 12: 3832

For reviews, see:
• 24a Gao H, Katzenellenbogen JA, Garg R, Hansch C. Chem. Rev. 1999; 99: 723
• 24b Alt HG, Köppl A. Chem. Rev. 2000; 100: 1205
• 24c Wang B. Coord. Chem. Rev. 2006; 250: 242

For reviews, see:
• 25a Stang PJ, Rappopoat Z, Hanack M, Subramanian LR. Vinyl Cations . Academic Press; New York: 1979
• 25b Dicoordinated Carbocations . Rappoport Z, Stang PJ. Wiley; Chichester: 1997
• 26 Li H.-H, Zhang X, Jin Y.-H, Tian S.-K. Asian J. Org. Chem. 2013; 2: 290

For the reaction of benzylic cations with alkenes to give more highly substituted alkenes, see:
• 27a Yue H.-L, Wei W, Li M.-M, Yang Y.-R, Ji J.-X. Adv. Synth. Catal. 2011; 353: 3139
• 27b Liu Z.-Q, Zhang Y, Zhao L, Li Z, Wang J, Li H, Wu L.-M. Org. Lett. 2011; 13: 2208
• 27c Peng S, Wang L, Wang J. Org. Biomol. Chem. 2012; 10: 225
• 27d Huang G.-B, Wang X, Pan Y.-M, Wang H.-S, Yao G.-Y, Zhang Y. J. Org. Chem. 2013; 78: 2742

For the reaction of benzylic cations with alkenes to give indanes, see:
• 28a Lantaño B, Aguirre JM, Ugliarolo EA, Benegas ML, Moltrasio GY. Tetrahedron 2008; 64: 4090
• 28b Li H, Li W, Liu W, He Z, Li Z. Angew. Chem. Int. Ed. 2011; 50: 2975
• 29 For a stereoselective synthesis of similar polysubstituted alkenes, see: Li H.-H, Jin Y.-H, Wang J.-Q, Tian S.-K. Org. Biomol. Chem. 2009; 7: 3219
• 30 Liu C.-R, Wang T.-T, Qi Q.-B, Tian S.-K. Chem. Commun. 2012; 48: 10913
• 31 For a related example, see: Meng B, Ma S. Org. Lett. 2012; 14: 2674

For reviews of electrophilic additions to allenes, see:
• 32a Ma S In Modern Allene Chemistry . Vol. 2. Krause N, Hashmi AS. K. Wiley-VCH; Weinheim: 2004: 595
• 32b Ma S. Pure Appl. Chem. 2007; 79: 261
• 32c Ma S. Acc. Chem. Res. 2009; 42: 1679
• 33 Fleming I, Barbero A, Walter D. Chem. Rev. 1997; 97: 2063
• 34 For weaker nucleophiles, such as organozinc reagents, more-reactive N-allylic sulfonimides were used, see: Tang X.-L, Wu Z, Li M.-B, Gu Y, Tian S.-K. Eur. J. Org. Chem. 2012; 4107
• 35a Enders D, Narine AA, Toulgoat F, Bisschops T. Angew. Chem. Int. Ed. 2008; 47: 5661
• 35b Sun F.-L, Zheng X.-J, Gu Q, He Q.-L, You S.-L. Eur. J. Org. Chem. 2010; 47
• 36 For a review of catalytic enantioselective stereoablative reactions that destroy stereogenic elements of a molecule, see: Mohr JT, Ebner DC, Stoltz BM. Org. Biomol. Chem. 2007; 5: 3571

For reviews on asymmetric catalysis using chiral phosphoric acids, see:
• 37a Akiyama T. Chem. Rev. 2007; 107: 5744
• 37b Terada M. Chem. Commun. 2008; 4097
• 37c Terada M. Synthesis 2010; 1929
• 37d Yu J, Shi F, Gong L.-Z. Acc. Chem. Res. 2011; 44: 1156

The stereoselectivity factor (s = k_fast /k_slow ) was not used to evaluate the reaction because this varies with the conversion; for reviews, see:
• 38a Keith JM, Larrow JF, Jacobsen EN. Adv. Synth. Catal. 2001; 343: 5
• 38b Vedejs E, Jure M. Angew. Chem. Int. Ed. 2005; 44: 3974
• 39a Kang Q, Zhao Z.-A, You S.-L. J. Am. Chem. Soc. 2007; 129: 1484
• 39b Xu F, Huang D, Han C, Shen W, Lin X, Wang Y. J. Org. Chem. 2010; 75: 8677
• 39c Xing C.-H, Liao Y.-X, Ng J, Hu Q.-S. J. Org. Chem. 2011; 76: 4125

For related examples, see:
• 40a Jia Y.-X, Zhong J, Zhu S.-F, Zhang C.-M, Zhou Q.-L. Angew. Chem. Int. Ed. 2007; 46: 5565
• 40b Lin J.-H, Xiao J.-C. Eur. J. Org. Chem. 2011; 4536
• 40c Cheng D.-J, Wu H.-B, Tian S.-K. Org. Lett. 2011; 13: 5636
• 40d Cheng D.-J, Tian Y, Tian S.-K. Adv. Synth. Catal. 2012; 354: 995
• 41 Liu C.-R, Li M.-B, Cheng D.-J, Yang C.-F, Tian S.-K. Org. Lett. 2009; 11: 2543
• 42 For a similar mechanism, see: Li H.-H, Dong D.-J, Jin Y.-H, Tian S.-K. J. Org. Chem. 2009; 74: 9501
• 43 Liu, C.-R.; Tian, S.-K. unpublished results.
• 44 Li H.-H, Dong D.-J, Tian S.-K. Eur. J. Org. Chem. 2008; 3623
• 45 Yang B.-L, Weng Z.-T, Yang S.-J, Tian S.-K. Chem. Eur. J. 2010; 16: 718
• 46 Nickon A, Sinz A. J. Am. Chem. Soc. 1960; 82: 753