Asymmetric One-Pot Synthesis of 1,3-Oxazolidines and 1,3-Oxazinanes via Hemiaminal Intermediates

Abstract

A highly efficient method for the enantioselective one-pot synthesis of 1,3-oxazolidines and 1,3-oxazinanes has been reported. The reaction proceeds via the formation of hemiaminal intermediates obtained by the enantioselective addition of respective alcohols to imines catalyzed by a chiral magnesium phosphate catalyst, followed by intramolecular cyclization under mildly basic conditions. A wide range of substrates have been converted to the respective chiral heterocyclic products in high yields and with excellent enantioselectivities using this one-pot procedure.

Recent Developments in the Stereoselective Synthesis of Nitrogen‐Containing Heterocycles using N‐Acylimines as Reactive Substrates

“…The synthetic operations leading to functionalized pyrrolidines from N ‐acylimines can be also carried out in several distinct steps with a suitable control of the last formed stereocenter. Upon reaction of N ‐acylimines with oxo ester 57 catalyzed by l ‐proline and subsequent reduction of the formyl group with NaBH 4 , adducts 58 are obtained as single diastereomers and with good enantioselectivity (Scheme ) . The O ‐silylated derivatives 59 can undergo an intramolecular aza‐Michael addition the diastereoselectivity of which is affected by the nature of the base employed to promote the reaction.…”

“…The asymmetric synthesis of 1,3‐oxazolidines 98 can be achieved by a one‐pot process starting with an enantioselective addition of 2‐chloroethanol to N ‐benzoylimines catalyzed by chiral magnesium salt 97 in ethyl acetate (Scheme ) …”

Enantioselective magnesium-catalyzed transformations

“…33 A recent example of enantioselective magnesium-catalyzed tandem reactions was described by Antilla et al, applied to the synthesis of chiral 1,3-oxazolidines and 1,3-oxazinanes under mild reaction conditions (Scheme 30). 54 The reaction began with the formation of hemiaminal intermediates 116 through enantioselective addition of the respective alcohols 117 to N-benzyl imines 118 catalyzed by the preformed chiral magnesium BINOL-derived phosphate catalyst 119, followed by intramolecular cyclization to give the final products 120 in good to excellent yields (77-99%) and enantioselectivities (80-97% ee). Generally, better yields (92-99% vs. 77-96%) and slightly higher enantioselectivities (83-97% ee vs. 80-95% ee) were achieved in the formation of 1,3-oxazinanes (n = 2) in comparison with 1,3-oxazolidines (n = 1).…”

Direct asymmetric N-propargylation of indoles and carbazoles catalyzed by lithium SPINOL phosphate

“…On the other hand, chiral alkali and alkaline earth metalderived salts of chiral phosphoric acids have recently emerged as a class of effective catalysts in various asymmetric transformations [41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60] . However, this class of chiral catalysts have not been successfully employed in the catalytic asymmetric functionalization of the N-H of indoles or carbazoles.…”