Synthesis of amines and amino acids via aluminum and boron reagents

Thomas E Burghardt, Purdue University

Abstract

Vinylalumination is a highly useful reaction for the preparation of functionalized allylic alcohols. Due to significantly shortened reaction times, accommodation for the β-substitution, and reactivity with ketones and fluorocarbonyls it is complimentary to the Baylis-Hillman protocol. Vinylalumination of various carbonyl compounds provided the desired 2° or 3° allylic alcohols. Vinylaluminations of keto-protected pyruvaldehyde provided the products, which were converted to α-alkylidene-β-hydroxy-γ-lactones. To show further applications for the vinylalumination reactions, β-substituted allylic amides and α-methylene-β-amino esters were prepared from the acetates of vinylalumination products via tandem SN2' substitution--reduction--[3,3]-sigmatropic rearrangement. The use of nitrogen nucleophile provided N-substituted β-amino esters in essentially one step from the vinylalumination products. Similar allylic dienyl amines were prepared via 'allyl'boration of α,β-unsaturated aldehydes with α-pinene-based 'allyl'boranes. The homoallylic alcohols were obtained in good yields and high de and ee and were converted to trichloroacetimidates and subjected to thermal [3,3]-sigmatropic rearrangement to yield allylic amides. Representative allylic amides were converted to the corresponding α-amino acids. Allylboration, crotylboration, and alkoxyallylboration of N-silyl and N-aluminoimines furnished, after the addition of 1.0 eq of methanol or water, the corresponding homoallylic amines in good yields, high de and ee. This is the first report of reagent-controlled crotyl and alkoxyallylboration of imines, which proceed only with the boron 'ate' complexes. To demonstrate the application of this methodology, representative amines were oxidized to β-amino acids, δ-amino alcohols, γ-amino acids, and γ-lactams. To show further application of the prepared homoallylic amines and to expand the use of the tandem vinylalumination and SN2' methodology, representative chiral functionalized tetrahydropyridines, known potent GABA-uptake and muscarinic inhibitors, were prepared.

Degree

Ph.D.

Advisors

Ramachandran, Purdue University.

Subject Area

Organic chemistry

COinS