New Perspectives in Lithium Carbenoid Mediated Homologations

Dedicated to Professor Friedrich Hammerschmidt on the occasion of his retirement

Abstract

α-Functionalized organolithium reagents (e.g., LiCH₂X) are versatile reagents for accomplishing homologations of carbon- and heteroatom-type electrophiles. The proper selection of the reaction conditions allows one to direct their intrinsic ambiphilicity towards the nucleophilic character. Herein, the homologation of various electrophiles ranging from Weinreb amides to isocyanates, carbonyl derivatives, and chalcogenides – with a particular focus on the chemoselectivity of the processes – is summarized.

1 Introduction

2 Homologation of Weinreb Amides

3 Homologation of Cyclic Ketones

4 Homologation of Isocyanates

5 Homologation of Disulfides and Diselenides

6 Conclusions

Key words

carbenoids - lithium - homologation - chemoselectivity - organometallic reagents

• References

• 1a Knochel P, Molander GA In Comprehensive Organic Synthesis . 2nd ed. Elsevier; Amsterdam: 2014
• 1b Pace V. Habilitation Thesis. University of Vienna; Austria: 2016
• 2 Pace V, Monticelli S, de la Vega-Hernandez K, Castoldi L. Org. Biomol. Chem. 2016; 14: 7848
• 3 Li JJ. Name Reactions for Homologation . Wiley; Hoboken: 2009
• 4a Köbrich G, Akhtar A, Ansari F, Breckoff WE, Büttner H, Drischel W, Fischer RH, Flory K, Fröhlich H, Goyert W, Heinemann H, Hornke I, Merkle HR, Trapp H, Zündorf W. Angew. Chem., Int. Ed. Engl. 1967; 6: 41
• 4b Boche G, Lohrenz JC. W. Chem. Rev. 2001; 101: 697
• 4c Braun M In The Chemistry of Organolithium Compounds . Rappoport Z, Marek I. John Wiley and Sons; Chichester: 2004
• 4d Capriati V In Contemporary Carbene Chemistry . John Wiley and Sons; Hoboken: 2013
• 4e Capriati V, Florio S. Chem. Eur. J. 2010; 16: 4152
• 4f Pace V, Holzer W, De Kimpe N. Chem. Rec. 2016; 16: 2061
• 4g Pace V. Aust. J. Chem. 2014; 67: 311
• 4h Luisi R, Capriati V. Lithium Compounds in Organic Synthesis: From Fundamentals to Applications. Wiley-VCH; Weinheim: 2014
• 4i Clayden J. Organolithiums: Selectivity for Synthesis . Pergamon Press; Oxford: 2002
• 4j Gessner VH. Chem. Commun. 2016; 52: 12011
• 5a Arndt F, Eistert B, Ender W. Chem. Ber. 1929; 62: 44
• 5b Candeias NR, Paterna R, Gois PM. P. Chem. Rev. 2016; 116: 2937
• 5c Ford A, Miel H, Ring A, Slattery CN, Maguire AR, McKervey MA. Chem. Rev. 2015; 115: 9981
• 5d Maas G. Angew. Chem. Int. Ed. 2009; 48: 8186
• 5e Pace V, Verniest G, Sinisterra JV, Alcántara AR, De Kimpe N. J. Org. Chem. 2010; 75: 5760
• 6a Corey EJ, Chaykovsky M. J. Am. Chem. Soc. 1962; 84: 867
• 6b Gololobov YG, Nesmeyanov AN, lysenko VP, Boldeskul IE. Tetrahedron 1987; 43: 2609
• 7a Molitor S, Gessner VH. Synlett 2015; 26: 861
• 7b Molitor S, Feichtner K.-S, Kupper C, Gessner VH. Chem. Eur. J. 2014; 20: 10752
• 7c Molitor S, Becker J, Gessner VH. J. Am. Chem. Soc. 2014; 136: 15517
• 7d Kupper C, Molitor S, Gessner VH. Organometallics 2014; 33: 347
• 7e Molitor S, Gessner VH. Chem. Eur. J. 2013; 19: 11858
• 7f Gessner VH, Däschlein C, Strohmann C. Chem. Eur. J. 2009; 15: 3320
• 8 Pasco M, Gilboa N, Mejuch T, Marek I. Organometallics 2013; 32: 942
• 9a Simmons HE, Smith RD. J. Am. Chem. Soc. 1958; 80: 5323
• 9b Charette AB, Beauchemin A In Organic Reactions . John Wiley and Sons; Chichester: 2004
• 10a Satoh T. Heterocycles 2012; 85: 1
• 10b Satoh T. Chem. Soc. Rev. 2007; 36: 1561
• 10c Avolio S, Malan C, Marek I, Knochel P. Synlett 1999; 1820
• 10d Hoffmann RW, Nell PG, Leo R, Harms K. Chem. Eur. J. 2000; 6: 3359
• 10e Hoffmann RW, Nell PG. Angew. Chem. Int. Ed. 1999; 38: 338
• 11a Nishimura RH. V, Murie VE, Soldi RA, Lopes JL. C, Clososki GC. J. Braz. Chem. Soc. 2015; 26: 2175
• 11b Nishimura RH. V, Murie VE, Soldi RA, Clososki GC. Synthesis 2015; 47: 1455
• 11c Nishimura RH. V, Toledo FT, Lopes JL. C, Clososki GC. Tetrahedron Lett. 2013; 54: 287
• 12 Köbrich G. Angew. Chem., Int. Ed. Engl. 1972; 11: 473
• 13 Sadhu KM, Matteson DS. Tetrahedron Lett. 1986; 27: 795
• 14a Barluenga J, Llavona L, Concellón JM, Yus M. J. Chem. Soc., Perkin Trans. 1 1990; 417
• 14b Barluenga J, Baragaña B, Alonso A, Concellón JM. J. Chem. Soc., Chem. Commun. 1994; 969
• 14c Barluenga J, Baragaña B, Concellón JM. J. Org. Chem. 1995; 60: 6696
• 15 Tarhouni R, Kirschleger B, Rambaud M, Villieras J. Tetrahedron Lett. 1984; 25: 835
• 16a Concellón JM, Cuervo H, Fernández-Fano R. Tetrahedron 2001; 57: 8983
• 16b Concellón JM, Rodríguez-Solla H, Simal C. Org. Lett. 2008; 10: 4457
• 16c Concellón JM, Rodríguez-Solla H, Bernad PL, Simal C. J. Org. Chem. 2009; 74: 2452
• 17 Savoia D, Alvaro G, Di Fabio R, Gualandi A, Fiorelli C. J. Org. Chem. 2006; 71: 9373
• 18a Matteson DS. J. Org. Chem. 2013; 78: 10009
• 18b Matteson DS, Majumdar D. Organometallics 1983; 2: 1529
• 18c Matteson DS, Majumdar D. J. Am. Chem. Soc. 1980; 102: 7588
• 19a Sonawane RP, Jheengut V, Rabalakos C, Larouche-Gauthier R, Scott HK, Aggarwal VK. Angew. Chem. Int. Ed. 2011; 50: 3760
• 19b Pulis AP, Blair DJ, Torres E, Aggarwal VK. J. Am. Chem. Soc. 2013; 135: 16054
• 19c Burns M, Essafi S, Bame JR, Bull SP, Webster MP, Balieu S, Dale JW, Butts CP, Harvey JN, Aggarwal VK. Nature (London, U.K.) 2014; 513: 183
• 19d Rasappan R, Aggarwal VK. Nat. Chem. 2014; 6: 810
• 19e Unsworth PJ, Leonori D, Aggarwal VK. Angew. Chem. Int. Ed. 2014; 53: 9846
• 19f Watson CG, Balanta A, Elford TG, Essafi S, Harvey JN, Aggarwal VK. J. Am. Chem. Soc. 2014; 136: 17370
• 19g Balieu S, Hallett GE, Burns M, Bootwicha T, Studley J, Aggarwal VK. J. Am. Chem. Soc. 2015; 137: 4398
• 20a Emerson CR, Zakharov LN, Blakemore PR. Chem. Eur. J. 2013; 19: 16342
• 20b Blakemore PR, Burge MS. J. Am. Chem. Soc. 2007; 129: 3068
• 20c Blakemore PR, Marsden SP, Vater HD. Org. Lett. 2006; 8: 773
• 20d Wu Z, Sun X, Potter K, Cao Y, Zakharov LN, Blakemore PR. Angew. Chem. Int. Ed. 2016; 55: 12285
• 21 Kapeller DC, Hammerschmidt F. J. Am. Chem. Soc. 2008; 130: 2329
• 22 Kail DC, Malova Krizkova P, Wieczorek A, Hammerschmidt F. Chem. Eur. J. 2014; 20: 4086
• 23 Degennaro L, Fanelli F, Giovine A, Luisi R. Adv. Synth. Catal. 2015; 357: 21
• 24 Kirmse W. Angew. Chem., Int. Ed. Engl. 1965; 4: 1
• 25 Loupy A, Tchoubar B. Salt Effects in Organic and Organometallic Chemistry. VCH; Weinheim: 1992
• 26a Dixon S, Fillery SM, Kasatkin A, Norton D, Thomas E, Whitby RJ. Tetrahedron 2004; 60: 1401
• 26b Mamuye AD, Castoldi L, Azzena U, Holzer W, Pace V. Org. Biomol. Chem. 2015; 13: 1969
• 27a Reeder MR, Anderson RM. Chem. Rev. 2006; 106: 2828
• 27b Honda Y, Katayama S, Kojima M, Suzuki T, Kishibata N, Izawa K. Org. Biomol. Chem. 2004; 2: 2061
• 27c Izawa K, Onishi T. Chem. Rev. 2006; 106: 2811
• 27d Pace V, Castoldi L, Pregnolato M. Mini-Rev. Med. Chem. 2013; 13: 988
• 28a Onishi T, Hirose N, Nakano T, Nakazawa M, Izawa K. Tetrahedron Lett. 2001; 42: 5883
• 28b Onishi T, Nakano T, Hirose N, Nakazawa M, Izawa K. Tetrahedron Lett 2001; 42: 5887
• 28c Onishi T, Otake Y, Hirose N, Nakano T, Torii T, Nakazawa M, Izawa K. Tetrahedron Lett. 2001; 42: 6337
• 28d Gohring W, Gokhale S, Hilpert H, Roessler F, Schlageter M, Vogt P. Chimia 1996; 50: 532
• 29a Pace V, Cortés-Cabrera Á, Fernández M, Sinisterra JV, Alcántara AR. Synthesis 2010; 3545
• 29b Pace V, Martínez F, Fernández M, Sinisterra JV, Alcántara AR. Adv. Synth. Catal. 2009; 351: 3199
• 29c Pace V, Castoldi L, Hernáiz MJ, Alcántara AR, Holzer W. Tetrahedron Lett. 2013; 54: 4369
• 30 Pace V, Holzer W, Verniest G, Alcántara AR, De Kimpe N. Adv. Synth. Catal. 2013; 355: 919
• 31 Adler M, Adler S, Boche G. J. Phys. Org. Chem. 2005; 18: 193
• 32a Nahm S, Weinreb SM. Tetrahedron Lett. 1981; 22: 3815
• 32b Balasubramaniam S, Aidhen IS. Synthesis 2008; 3707
• 32c Pace V, Holzer W, Olofsson B. Adv. Synth. Catal. 2014; 356: 3697
• 32d Pace V, Holzer W. Aust. J. Chem. 2013; 66: 507
• 33 Pace V, Castoldi L, Holzer W. J. Org. Chem. 2013; 78: 7764
• 34 Ke Z, Zhou Y, Gao H, Zhao C, Phillips DL. Chem. Eur. J. 2007; 13: 6724
• 35a Fetter J, Nagy I, Giang LT, Kajtar-Peredy M, Rockenbauer A, Korecz L, Czira G. J. Chem. Soc., Perkin Trans. 1 2001; 1131
• 35b Rasmussen JK, Hassner A. Synthesis 1973; 682
• 35c Chiba T, Okimoto M. J. Org. Chem. 1991; 56: 6163
• 36a Guijarro A, Yus M. Tetrahedron Lett. 1993; 34: 3487
• 36b Guijarro A, Mancheño B, Ortiz J, Yus M. Tetrahedron 1996; 52: 1643
• 37 Pace V, Murgia I, Westermayer S, Langer T, Holzer W. Chem. Commun. 2016; 52: 7584
• 38 Lautens M, Maddess ML, Sauer EL. O, Ouellet SG. Org. Lett. 2001; 4: 83
• 39 Pace V, Castoldi L, Holzer W. Adv. Synth. Catal. 2014; 356: 1761
• 40 Pace V, Castoldi L, Hoyos P, Sinisterra JV, Pregnolato M, Sánchez-Montero JM. Tetrahedron 2011; 67: 2670
• 41 Gorokhovik I, Neuville L, Zhu J. Org. Lett. 2011; 13: 5536
• 42 Mamuye AD, Monticelli S, Castoldi L, Holzer W, Pace V. Green Chem. 2015; 17: 4194
• 43a Pace V, Castoldi L, Mamuye AD, Langer T, Holzer W. Adv. Synth. Catal. 2016; 358: 172
• 43b Chodnekar MS, Crowther AF, Hepworth W, Howe R, McLoughlin BJ, Mitchell A, Rao BS, Slatcher RP, Smith LH, Stevens MA. J. Med. Chem. 1972; 15: 49
• 43c Kennewell PD, Miller DJ, Scrowston RM, Westwood R. J. Chem. Soc., Miniprint 1995; 10: 2380
• 43d Chouhan M, Senwar KR, Sharma R, Grover V, Nair VA. Green Chem. 2011; 13: 2553
• 43e Hajra S, Maity S, Maity R. Org. Lett. 2015; 17: 3430
• 44a Allen AD, Tidwell TT. Chem. Rev. 2013; 113: 7287
• 44b Delebecq E, Pascault J.-P, Boutevin B, Ganachaud F. Chem. Rev. 2013; 113: 80
• 45 Gilman H, Kinney CR. J. Am. Chem. Soc. 1924; 46: 493
• 46a Padwa A, Crawford KR, Rashatasakhon P, Rose M. J. Org. Chem. 2003; 68: 2609
• 46b Antczak MI, Ready JM. Chem. Sci. 2012; 3: 1450
• 46c Ach D, Reboul V, Metzner P. Eur. J. Org. Chem. 2002; 2573
• 47a Schäfer G, Bode JW. Chimia 2014; 68: 252
• 47b Schäfer G, Matthey C, Bode JW. Angew. Chem. Int. Ed. 2012; 51: 9173
• 48 Pace V, Castoldi L, Holzer W. Chem. Commun. 2013; 49: 8383
• 49 Pace V, Castoldi L, Mamuye AD, Holzer W. Synthesis 2014; 46: 2897
• 50 Pace V, de la Vega-Hernández K, Urban E, Langer T. Org. Lett. 2016; 18: 2750
• 51 Hoppe D, Hintze F, Tebben P. Angew. Chem., Int. Ed. Engl. 1990; 29: 1422
• 52 Kerrick ST, Beak P. J. Am. Chem. Soc. 1991; 113: 9708
• 53 Pace V, Castoldi L, Monticelli S, Safranek S, Roller A, Langer T, Holzer W. Chem. Eur. J. 2015; 21: 18966
• 54a Lhermet R, Ahmad M, Fressigné C, Silvi B, Durandetti M, Maddaluno J. Chem. Eur. J. 2014; 20: 10249
• 54b Boddaert T, François C, Mistico L, Querolle O, Meerpoel L, Angibaud P, Durandetti M, Maddaluno J. Chem. Eur. J. 2014; 20: 10131
• 54c Negishi E, Akiyoshi K, O’Connor B, Takagi K, Wu G. J. Am. Chem. Soc. 1989; 111: 3089
• 55a Field L, Banks CH. J. Org. Chem. 1975; 40: 2774
• 55b Field L, Chu H.-K. J. Org. Chem. 1977; 42: 1768
• 56 Petragnani N, Schill G. Chem. Ber. 1970; 103: 2271
• 57 Pace V, Pelosi A, Antermite D, Rosati O, Curini M, Holzer W. Chem. Commun. 2016; 52: 2639
• 58a Giannerini M, Fañanás-Mastral M, Feringa BL. Nat. Chem. 2013; 5: 667
• 58b Giannerini M, Hornillos V, Vila C, Fañanás-Mastral M, Feringa BL. Angew. Chem. Int. Ed. 2013; 52: 13329
• 58c Vila C, Giannerini M, Hornillos V, Fananas-Mastral M, Feringa BL. Chem. Sci. 2014; 5: 1361

For highlights, see:
• 58d Pace V, Luisi R. ChemCatChem 2014; 6: 1516
• 58e Capriati V, Perna FM, Salomone A. Dalton Trans. 2014; 43: 14204
• 58f Firth JD, O’Brien P. ChemCatChem 2015; 7: 395