Chiral Auxiliary Based Reductive Alkylation of α,α‐Diallkyl β‐Phosphonyl Esters

Abstract

Acyclic a,a-disubstituted b-phosphonyl esters containing chiral alcoholic auxiliaries were efficiently prepared and evaluated for the lithium naphthalenide-mediated asymmetric reductive alkylation. Among which, the best diastereoselectivity was received from the substrates bearing a (-)-phenylmenthyl group in leading to alkylated esters with up to 83:17 dr. The diastereoselectivity is proven to be controlled by the p-facial differentiation created by the chiral ester as well as the geometry of tetrasubstituted enolates generated by the reductive cleavage of C-P bond.Our previous study demonstrated that the cyclic bphosphonyl esters derived from the Diels-Alder reaction of triethyl 2-phosphono-2-alkenoates underwent the facile dephosphonylation by treating with lithium naphthalenide Scheme I Gleason´s approach for asymmetric creation of quaternary carbons 532 www.jccs.wiley-vch.de HRMS-EI m/z [M]+ calcd for C 26 H 43 O 5 P 466.2848, found 466.2857. (1R,2S,5R)-2-(Diethoxy-phosphoryl)-2-methyl-pentanoic acid 2-isopropyl-5-methyl-cyclohexyl ester (2b)From 1b, the typical procedure of preparing 2a was followed by using iodopropane and iodomethane as the alkylating

Sequential Deprotonation–Alkylation of Binaphthyloxy-Substituted Phosphonochalcogenoates: Chiral Tri- and Tetrasubstituted Carbon Centers Adjacent to a Phosphorus Atom

“…To construct rare examples of chiral tetrasubstituted carbon centers, in particular, with three carbon-containing substituents, adjacent to a phosphorus atom, we then attempted the lithiation of ester 6h (Table ). However, under a variety of reaction conditions employing other bases and increasing the reaction temperature, the lithiation was unsuccessful and 6h remained mostly intact.…”