Convenient and Practical Alkynylation of Heteronucleophiles with Copper Acetylides

Dedicated to Prof. François Couty on the occasion of his 50^th birthday

Abstract

Copper acetylides, readily available reagents which are characterized by their lack of reactivity, can be simply activated by oxidation with oxygen in the presence of simple nitrogen ligands such as TMEDA or imidazole derivatives. Upon activation, these nucleophilic species undergo a formal umpolung and can transfer their alkyne subunit to a wide range of heteronucleophiles, including amides, oxazolidinones, imines, and dialkyl phosphites. This alkynylation, which provides one of the most practical entry to useful building blocks such as ynamides, ynimines, and alkynylphosphonates, proceeds under especially mild conditions and can be easily performed on a multigram scale.

Key words

copper acetylides - alkynylation - ynamides - ynimines - alkynylphosphonates

• References

• 1 For a recent review on metal-catalyzed synthesis of hetero-substituted alkynes, see: Evano G, Gaumont A.-C, Alayrac C, Wrona IE, Giguere JR, Delacroix O, Bayle A, Jouvin K, Theunissen C, Gatignol J, Silvanus AC. Tetrahedron 2014; 70: 1529

For recent reviews on the chemistry of nitrogen-substituted alkynes, see:
• 2a Evano G, Coste A, Jouvin K. Angew. Chem. Int. Ed. 2010; 49: 2840
• 2b DeKorver KA, Li H, Lohse AG, Hayashi R, Lu Z, Zhang Y, Hsung RP. Chem. Rev. 2010; 110: 5064
• 2c Evano G, Jouvin K, Coste A. Synthesis 2013; 45: 17
• 2d Wang X.-N, Yeom H.-S, Fang L.-C, He S, Ma Z.-X, Kedrowski BL, Hsung RP. Acc. Chem. Res. 2014; 47: 560

For recent general references on the chemistry of oxygen-substituted alkynes, see:
• 3a Witulski B, Alayrac C In Science of Synthesis: Houben-Weyl Methods of Molecular Transformations . Vol. 24. de Meijere A. Thieme; Stuttgart: 2005: 933-956
• 3b Potapov VA, Trofimov BA In Science of Synthesis: Houben-Weyl Methods of Molecular Transformations . Vol. 24. de Meijere A. Thieme; Stuttgart: 2005: 957-1005

For recent general references on the chemistry of phosphorus-substituted alkynes, see:
• 4a Pietrusiewicz KM, Stankević M. In Science of Synthesis: Houben-Weyl Methods of Molecular Transformations . Vol. 24. de Meijere A. Thieme; Stuttgart: 2005: 1073-1086
• 4b Kondoh A, Yorimitsu H, Oshima K. Chem. Asian J. 2010; 5: 398
• 4c Bernoud E, Veillard R, Alayrac C, Gaumont A.-C. Molecules 2012; 17: 14573
• 5a Frederick MO, Mulder JA, Tracey MR, Hsung RP, Huang J, Kurtz KC. M, Shen L, Douglas CJ. J. Am. Chem. Soc. 2003; 125: 2368
• 5b Dunetz JR, Danheiser RL. Org. Lett. 2003; 5: 4011
• 5c Zhang Y, Hsung RP, Tracey MR, Kurtz KC. M, Vera EL. Org. Lett. 2004; 6: 1151
• 5d Hamada T, Ye X, Stahl SS. J. Am. Chem. Soc. 2008; 130: 833
• 5e Coste A, Karthikeyan G, Couty F, Evano G. Angew. Chem. Int. Ed. 2009; 48: 4381
• 5f Jia W, Jiao N. Org. Lett. 2010; 12: 2000
• 5g Jouvin K, Couty F, Evano G. Org. Lett. 2010; 12: 3272
• 5h Sueda T, Oshima A, Teno N. Org. Lett. 2011; 13: 3996
• 5i DeKorver KA, Walton MC, North TD, Hsung RP. Org. Lett. 2011; 13: 4862
• 5j Laouiti A, Rammah MM, Rammah MB, Marrot J, Couty F, Evano G. Org. Lett. 2012; 14: 6
• 5k Wang L, Huang H, Priebbenow DL, Pan F.-F, Bolm C. Angew. Chem. Int. Ed. 2013; 52: 3478
• 6a Lera M, Hayes CJ. Org. Lett. 2000; 2: 3873
• 6b Beletskaya IP, Afanasiev VV, Kazankova MA, Efimova IV. Org. Lett. 2003; 5: 4309
• 6c Afanasiev VV, Beletskaya IP, Kazankova MA, Efimova IV, Antipin MU. Synthesis 2003; 2835
• 6d Gao Y, Wang G, Chen L, Xu P, Zhao Y, Zhou Y, Han L.-B. J. Am. Chem. Soc. 2009; 131: 7956
• 6e Hu J, Zhao N, Yang B, Wang G, Guo L.-N, Liang Y.-M, Yang S.-D. Chem. Eur. J. 2011; 17: 5516
• 6f Bernoud E, Alayrac C, Delacroix O, Gaumont A.-C. Chem. Commun. 2011; 47: 3239
• 6g Berger O, Petit C, Deal EL, Montchamp J.-L. Adv. Synth. Catal. 2013; 355: 1361
• 7 Normant JF. Synthesis 1972; 63

For general references on the oxidation of organocopper reagents, see:
• 8a Surry DS, Spring DA. Chem. Soc. Rev. 2006; 35: 218
• 8b Aves SJ, Spring DR In The Chemistry of Functional Groups. The Chemistry of Organocopper Compounds . Vol. 24. Rappoport Z, Marek I. Wiley; Chichester: 2009: 585-602
• 9a Jouvin K, Heimburger J, Evano G. Chem. Sci. 2012; 3: 756
• 9b Laouiti A, Jouvin K, Rammah MM, Rammah MB, Evano G. Synthesis 2012; 44: 1491
• 9c Jouvin K, Veillard R, Theunissen C, Alayrac C, Gaumont A.-C, Evano G. Org. Lett. 2013; 15: 4592
• 10a Nast R, Pfab W. Chem. Ber. 1956; 89: 415
• 10b Blake D, Calvin G, Coates GE. Proc. Chem. Soc. 1959; 396
• 10c Stephens RD, Castro CE. J. Org. Chem. 1963; 28: 3313
• 10d Atkinson RE, Curtis RF, Taylor JA. J. Chem. Soc. C 1967; 578
• 10e Owsley DC, Castro CE. Org. Synth. Coll. Vol. 6 . Wiley; New York: 1988: 916
• 11 Except for the copper derivatives of acetylene and p-diethynylbenzene, alkynylcopper reagents are stable to shock and heat: Royer EC, Barral MC, Moreno V, Santos A. J. Inorg. Nucl. Chem. 1981; 43: 705
• 12 Wei L.-L, Mulder JA, Xiong H, Zificsak CA, Douglas CJ, Hsung RP. Tetrahedron 2001; 57: 459
• 13 Gourdet B, Rudkin ME, Watts CA, Lam HW. J. Org. Chem. 2009; 74: 7849
• 14 He G, Zhang Q, Huang H, Chen S, Wang Q, Zhang D, Zhang R, Zhu H. Eur. J. Org. Chem. 2013; 6979
• 15 Al-Rashid ZF, Hsung RP. Org. Lett. 2008; 10: 661
• 16 Kramer S, Odabachian Y, Overgaard J, Rottländer M, Gagosz F, Skrydstrup T. Angew. Chem. Int. Ed. 2011; 50: 5090
• 17 Liu P, Yang J, Li P, Wang L. Appl. Organomet. Chem. 2011; 25: 83