Synthesis 2021; 53(01): 182-192
DOI: 10.1055/s-0040-1707351
paper
© Georg Thieme Verlag Stuttgart · New York

Diastereoselective Synthesis of Alkylated 1,4-Cyclohexadiene Esters Using Epimeric Pyrroloimidazolones

Ngan Tran
,
Dusty Cadwallader
,
Costa Metallinos
Department of Chemistry, Brock University, 1812 Sir Isaac Brock Way, St. Catharines, ON, L2S 3A1, Canada   Email: [email protected]
› Author Affiliations
This work was supported by NSERC Canada under the Discovery Grant program.
Further Information

Publication History

Received: 14 June 2020

Accepted after revision: 13 July 2020

Publication Date:
24 August 2020 (online)


Abstract

A pair of ortho-benzoate esters containing epimeric pyrroloimidazolones undergo sequential Birch reduction and diastereoselective alkylation to provide products ranging from 88:12 to >95:5 diastereomeric ratio (dr) for the syn-epimer, and 50:50 to 95:5 dr for the anti-epimer. The stereochemistry of the products is confirmed by a combination of X-ray crystallography on a key anti-epimer-derived product, in combination with specific rotation measurements of enantiomers that are prepared from the syn or anti starting materials. A diastereomerically pure allyl-substituted substrate is shown to undergo Cope rearrangement, which transposes the quaternary chiral center to a remote position without racemization. This work is complementary to asymmetric reductive alkylation reported previously by Schultz using anisole substrates with chiral benzamide auxiliaries in that the pyrroloimidazolones act as surrogates for the methoxy group.

Supporting Information

 
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