TY - JOUR
T1 - Practical and highly selective sulfur ylide-mediated asymmetric epoxidations and aziridinations using a cheap and readily available chiral sulfide
T2 - Extensive studies to map out scope, limitations, and rationalization of diastereo- and enantioselectivities
AU - Illa, Ona
AU - Namutebi, Mariam
AU - Saha, Chandreyee
AU - Ostovar, Mehrnoosh
AU - Chen, C. Chun
AU - Haddow, Mairi F.
AU - Nocquet-Thibault, Sophie
AU - Lusi, Matteo
AU - McGarrigle, Eoghan M.
AU - Aggarwal, Varinder K.
PY - 2013/8/14
Y1 - 2013/8/14
N2 - The chiral sulfide, isothiocineole, has been synthesized in one step from elemental sulfur, γ-terpinene, and limonene in 61% yield. A mechanism involving radical intermediates for this reaction is proposed based on experimental evidence. The application of isothiocineole to the asymmetric epoxidation of aldehydes and the aziridination of imines is described. Excellent enantioselectivities and diastereoselectivities have been obtained over a wide range of aromatic, aliphatic, and α,β-unsaturated aldehydes using simple protocols. In aziridinations, excellent enantioselectivities and good diastereoselectivities were obtained for a wide range of imines. Mechanistic models have been put forward to rationalize the high selectivities observed, which should enable the sulfide to be used with confidence in synthesis. In epoxidations, the degree of reversibility in betaine formation dominates both the diastereoselectivity and the enantioselectivity. Appropriate tuning of reaction conditions based on understanding the reaction mechanism enables high selectivities to be obtained in most cases. In aziridinations, betaine formation is nonreversible with semistabilized ylides and diastereoselectivities are determined in the betaine forming step and are more variable as a result.
AB - The chiral sulfide, isothiocineole, has been synthesized in one step from elemental sulfur, γ-terpinene, and limonene in 61% yield. A mechanism involving radical intermediates for this reaction is proposed based on experimental evidence. The application of isothiocineole to the asymmetric epoxidation of aldehydes and the aziridination of imines is described. Excellent enantioselectivities and diastereoselectivities have been obtained over a wide range of aromatic, aliphatic, and α,β-unsaturated aldehydes using simple protocols. In aziridinations, excellent enantioselectivities and good diastereoselectivities were obtained for a wide range of imines. Mechanistic models have been put forward to rationalize the high selectivities observed, which should enable the sulfide to be used with confidence in synthesis. In epoxidations, the degree of reversibility in betaine formation dominates both the diastereoselectivity and the enantioselectivity. Appropriate tuning of reaction conditions based on understanding the reaction mechanism enables high selectivities to be obtained in most cases. In aziridinations, betaine formation is nonreversible with semistabilized ylides and diastereoselectivities are determined in the betaine forming step and are more variable as a result.
UR - http://www.scopus.com/inward/record.url?scp=84882256472&partnerID=8YFLogxK
U2 - 10.1021/ja405073w
DO - 10.1021/ja405073w
M3 - Article
AN - SCOPUS:84882256472
SN - 0002-7863
VL - 135
SP - 11951
EP - 11966
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 32
ER -