Synthesis of amino acid derivatives via vinylalumination and hydroboration
Abstract
The addition of a vinylaluminum species across aldehydes or imines to afford the corresponding allylic alcohols or amines is termed as vinylalumination. This reaction allows the inclusion of several functional groups on the vinyl moiety for the convenient synthesis of functionalized allyl alcohols and amines. For example, vinylalumination has been used for the preparation of α-alkylidene-β-hydroxy esters. Due to its shorter reaction time, compatibility with fluorocarbonyls, and accommodation of β-substitution, it can be considered a superior alternative to the Baylis-Hillman reaction. Hydroalumination of ethyl-2-butynoate followed by reaction with aldehydes provides exclusively Z-crotonates. Addition of LDA to the reaction followed by quenching with a bulky proton source provides the E-crotonates in one pot. Further application has been demonstrated by the addition of the aluminate intermediate to aldehydes and ketones to furnish 1,5-diols. Conversion of vinylalumination alcohols to acetates, followed by SN2' reaction with a variety of nucleophiles gives substituted α,β-unsaturated esters. A series of GABA-uptake inhibitor analogs were prepared by the nucleophilic attack of a chiral allylic amine onto vinylalumination acetates, followed by protection and ring-closing metathesis. The SN2' tandem conjugate addition-elimination by the Schiff base of benzophenone tert-butyl ester onto vinylalumination acetates using a chiral phase-transfer catalyst gives 4-alkylidenyl glutamic acid derivatives. Hydroboration of fluorostyrenes with BH2I·SMe2 followed by oxidation or amination selectively afforded the corresponding primary alcohols and amines, respectively. Conversion of the intermediate borane to the 9-BBN derivative, followed by boron alkylation of a Schiff base cation equivalent provided fluoroamino acid derivatives.
Degree
Ph.D.
Advisors
Ramachandran, Purdue University.
Subject Area
Organic chemistry
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