A Novel One-Pot Procedure for the Stereoselective Synthesis of α-Hydroxy Esters from Ortho Esters

Abstract

A novel one-pot procedure for the stereoselective synthesis of alpha-hydroxy esters from ortho esters was developed. Key steps were multi-heteroatom Cope rearrangements of O-acylated N-hydroxy-l-tert-leucinol-derived oxazoline N-oxides leading to alpha-acyloxy oxazolines and, after methanolysis, to the target molecules in 67-80% yield and 94-98% ee.

C−H Reactivity of the α‐Position in Nitrones and Nitronates

“…A similar process was reported using N ‐hydroxy‐1,2‐amino alcohols 142 as chiral auxiliary groups (Scheme ) . As expected, the stereoselectivity of the [3,3]‐rearrangement was highly dependent on the R substituent.…”

“…The process shown in Scheme can be utilized to transform orthoesters into enantiomerically enriched α‐hydroxy carboxylic acids …”

Chemistry without Bo(a)rders

“…[7] The objective of my research work was to gain access to enantiomerically pure α-amino acids or α-hydroxy esters in a one-pot procedure from various ortho esters by exploiting the multi heteroatom Cope rearrangement as the key step of the synthesis (Scheme 1). The application of this method in the synthesis of methylesters of un/naturally occurring α-hydroxy acids such as l-phenyllactic acid proved to be very successful and presents a novel way for the preparation of these important synthetic building blocks.…”

“…Even though I was pretty self-sufficient when it came to laboratory work, owing to my independent research at MIT, I still had to learn a lot when it General scheme for the stereoselective synthesis of various R-hydroxy esters from the corresponding ortho esters employing the multi heteroatom Cope rearrangement (MHACR) in a one-pot procedure. [7] came to puzzling out what undesired pathway a reaction had taken or how to cope with the constant failure we experience in every day lab life. (Let us be honest, as a scientist in lab we have more of the cuss word moments than the eureka moments.…”

α-Amination of keto-nitrones via Multihetero-Cope rearrangement employing an imidoyl chloride reagent

“…Several substituted benzyl nitrones were examined, with the tolyl group providing the highest yield ( 14 ). A chiral nitrone derived from ( S )-α-methyl benzylamine was synthesized and tested, 11 but chirality transfer was poor ( 18 ).…”