ORGANIC LETTERS
Efficient N-Heterocyclic Carbene-Catalyzed O- to C-Acyl Transfer
2006 Vol. 8, No. 17 3785-3788
Jennifer E. Thomson, Kathryn Rix, and Andrew D. Smith* EaStChem, School of Chemistry and Centre for Biomolecular Sciences, UniVersity of St Andrews, North Haugh, St Andrews, KY16 9ST, U.K.
[email protected] Received June 6, 2006
ABSTRACT
An N-heterocyclic carbene promotes the rearrangement of r-amino acid derived O-acyl carbonates to their corresponding C-acylated isomers, generating a C−C bond and a quaternary stereocenter with high efficiency, under mild reaction conditions and with low catalyst loadings.
N-Heterocyclic carbenes (NHCs) have recently been shown to promote a range of organocatalytic reactions.1 Within this rapidly expanding field of research, two mechanistically distinct reaction pathways are widely recognized, involving the use of NHCs as either acyl anion equivalents or acyl transfer reagents. The ability of NHCs to generate acyl anion equivalents for C-C bond-forming applications has been demonstrated for benzoin- and Stetter-type transformations2 and has been extended to nucleophilic substitution3 and homoenolate reactions,4 although these reaction protocols typically require >5 mol % of catalyst. NHCs have been utilized as catalytic acyl transfer agents to promote trans(1) For selected reviews, see: Enders, D.; Balensiefer, T. Acc. Chem. Res. 2004, 37, 534. Johnson, J. S. Angew. Chem., Int. Ed. 2004, 43, 1326. (2) Teles, J. H.; Melder, J.-P.; Ebel, K.; Schneider, R.; Gehrer, E.; Harder, W.; Brode, S.; Enders, D.; Breuer, K.; Raabe, G. HelV. Chim. Acta 1996, 79, 61. Enders, D.; Breuer, K.; Teles, J. H. HelV. Chim. Acta 1996, 79, 1217. Enders, D.; Breuer, K.; Runsink, J.; Teles, J. H. HelV. Chim. Acta 1996, 79, 1899. Enders, D.; Kallfass, U. Angew. Chem., Int. Ed. 2002, 41, 1743. Kerr, M. S.; de Alaniz, J. R.; Rovis, T. J. Am. Chem. Soc. 2002, 124, 10298. Chow, K. Y. K.; Bode, J. W. J. Am. Chem. Soc. 2004, 126, 8216. Reynold, N. T.; de Alaniz, J. R.; Rovis, T. J. Am. Chem. Soc. 2004, 126, 9518. Myers, M. C.; Bharadwaj, A. R.; Milgram, B. C.; Scheidt, K. A. J. Am. Chem. Soc. 2005, 127, 14675. (3) Suzuki, Y.; Toyota, T.; Imada, F.; Sato, M.; Miyashita, A. Chem. Commun. 2003, 1314. 10.1021/ol061380h CCC: $33.50 Published on Web 07/15/2006
© 2006 American Chemical Society
esterification reactions,5-7 and these methods have been extended to the kinetic resolution of racemic alcohols using chiral NHCs.8 Although these resolutions proceed with high levels of stereoselectivity, relatively high catalyst loadings (typically 5-30 mol %) and long reaction times (up to 48 h) are needed to achieve significant reaction conversion. To date, applications of NHCs as catalytic acyl transfer reagents have been limited to acyl transfer to alcohols;9 to the best of our knowledge, their application in truly catalytically (4) For selected examples, see: Burstein, C.; Glorius, F. Angew. Chem., Int. Ed. 2004, 43, 6205. Sohn, S. S.; Rosen, E. L.; Bode, J. W. J. Am. Chem. Soc. 2004, 126, 14370. Chan, A.; Scheidt, K. A. Org. Lett. 2005, 7, 905. (5) Grasa, G. A.; Kissling, R. M.; Nolan, S. P. Org. Lett. 2002, 4, 3583. Grasa, G. A.; Gu¨veli, T.; Singh, R.; Nolan, S. P. J. Org. Chem. 2003, 68, 2812. (6) Connor, E. F.; Nyce, G. W.; Myers, M.; Mo¨ck, A.; Hedrick, J. L. J. Am. Chem. Soc. 2002, 124, 914. Nyce, G. W.; Lamboy, J. A.; Connor, E. F.; Waymouth, R. M.; Hedrick, J. L. Org. Lett. 2002, 4, 3587. Nyce, G. W.; Glauser, T.; Connor, E. F.; Mo¨ck, A.; Waymouth, R. M.; Hedrick, J. L. J. Am. Chem. Soc. 2003, 125, 3046. (7) Movassaghi and Schmidt have proposed that NHCs function as carbon-centred Bronsted bases: Movassaghi, M.; Schmidt, M. A. Org. Lett. 2005, 7, 2453. (8) Suzuki, Y.; Maramatsu, K.; Yamauchi, K.; Morie, Y.; Sato, M. Chem. Commun. 2004, 2770. Kano, T.; Sasaki, K.; Maruoka, K. Org. Lett. 2005, 7, 1347. Suzuki, Y.; Maramatsu, K.; Yamauchi, K.; Morie, Y.; Sato, M. Tetrahedron 2006, 62, 302.
efficient C-C bond-forming reactions has not been demonstrated. In 1970, Steglich and Ho¨fle showed that DMAP and 4-(pyrrolidino)pyridine could act as nucleophilic catalysts and promote the rearrangement of 5-acyloxyoxazole derivatives to their corresponding 4- or 2-acyl-azlactones.10 This process allows access to synthetically useful R,R-disubstituted R-amino acid derivatives,11-13 although the regioselectivity of this transformation is dependent upon both the steric and electronic nature of the 2- and 4-substituents of the acyloxyoxazole. Fu11 and Vedejs,12 among others,13 have elegantly shown that chiral DMAP derivatives can induce enantiocontrol in this reaction. Herein, we report that NHCs can also promote the efficient rearrangement of O-acyl carbonates to their corresponding C-acylated isomers with low catalyst loadings (
