Dearomative [2,3] sigmatropic rearrangement of ammonium ylides followed by 1,4-elimination to form α-(ortho-vinylphenyl)amino acid esters

Abstract

A base-induced dearomative [2,3] sigmatropic rearrangement of amino acid ester-derived ammonium salts followed by 1,4-elimination produced α-(ortho-vinylphenyl)amino acid esters. The reaction of azetidine-2-carboxylic acid-derived ammonium salt, (1S,2S,1'R)-3b, proceeded with a perfect N-to-C chirality transfer to afford α-(ortho-vinylphenyl)azetidine-2-carboxylic acid ester, (R)-5 (99% ee). On the other hand, the reaction of glycine-derived ammonium salt (R)-6a, which involves an efficient chirality transfer from a chiral benzylic carbon to an α-carbon of an ester carbonyl giving the optically active α-(ortho-vinylphenyl)glycine ester, (R)-8a (85% ee), was demonstrated. Although this dearomative [2,3] rearrangement followed by 1,4-elimination has limitations with regard to the structures of the substrates, our method provides unique access to substituted α-arylamino acid derivatives.

Recent Advances in the Generation of Onium Ylides for Sommelet–Hauser Rearrangements

“…Successive dearomative [2,3] sigmatropic rearrangements followed by 1,4-elimination was achieved as a further application of the rearrangement of N-(α-branched)benzylic salts (Scheme 17). 27 The presence of an α-acetoxymethyl substituent in the N-(α-branched)benzylic migrating group, such as in (1S,2S,1'R)-71, resulted in the in situ conversion of the corresponding dearomatized intermediate 72 to the orthovinylphenyl derivative (R)-75 by base-promoted 1,4-elimination of 73. This transformation requires 2 equivalents of tBuOK to obtain (R)-75 in a high yield.…”

Diastereoselective Indole-Dearomative Cope Rearrangements by Compounding Minor Driving Forces

“…This is because of the generally favorable kinetics and thermodynamics of such systems. There is a rich variety of “heteroatomic 1,5-diene” substrate classes reported (Figure A), − including many “named reactions” (aromatic Claisen and Sommelet–Hauser , rearrangements and Fischer indole synthesis). The aromatic Cope rearrangement is significantly more limited with few modern examples that can be applied to complex molecule synthesis .…”

“…Experimental procedures and characterization data ( 1 H NMR, 13 C NMR, 19 F NMR, HRMS, X-ray, and HPLC traces) (PDF)…”