Retro-aza-Michael reaction in continuous flow. Approaches to synthesis of adaline and euphococcinine related products

A retro-aza-Michael ring opening reaction of tropinone and granatanone (pseudopelletierine) in flow setup was investigated and the resulting products were utilized as key intermediates in approaches to adaline and its analogues. The enantioselective flow-reaction gave products of ring opening of gran-atanone with enantiopurity up to 98% ee. Attempts to elaborate the retro-aza-Michael product to alka-loids are described. Lithiated carbamate derivative of tropane was converted to a tropane analogue of euphococcinine, an adaline related alkaloid (a methyl and tropane homologue of adaline 19). Reactivity of the retro-aza-Michael product under Morita-Baylis-Hillman conditions was also briefly investigated. (c) 2022 Elsevier Ltd. All rights reserved.