Bioinspired enantioselective synthesis of crinine-type alkaloids via iridium-catalyzed asymmetric hydrogenation of enones

Abstract

A bioinspired enantioselective synthesis of crinine-type alkaloids was developed by iridium-catalyzed asymmetric hydrogenation of enones, providing 24 crinine-type alkaloids and 8 analogues with high yield and high enantioselectivity.

Synthetic routes to crinine and vittatine

“…[17] Subsequently, the removal of the Nprotecting group in 86 (or 87) was followed by a conjugate S C H E M E 2 0 Zhou's asymmetric synthesis addition to furnish oxocrinine, which is a well-established intermediate en route to crinine. [22,23] S anchez et al took advantage of a hydroazepinyl aldehyde 91 as a springboard to establish a N-protected spirocyclic enone 92 (Scheme 17). [24] The benzohydroazepine nucleus (90) was assembled through a Tscherniac-Einhorn reaction of N-hydroxymethylated carbamate 89.…”

“…Scheme 17), and this accordingly constitutes a formal synthesis of (±)-crinine. [22,23] Zhou and coworkers demonstrated a stereodivergent reductive resolution of racemic oxocrinine leading to the facile syntheses of (À)-crinine and (+)-vittatine (Scheme 20). [23] In this study, (±)-oxocrinine was prepared by the known four-step process (via the spirocyclic intermediate).…”

“…[ 17 ] Subsequently, the removal of the N ‐protecting group in 86 (or 87 ) was followed by a conjugate addition to furnish oxocrinine, which is a well‐established intermediate en route to crinine. [ 22,23 ]…”

The Chemical Synthesis of the Crinine and Haemanthamine Alkaloids: Biologically Active and Enantiomerically-Related Systems that Serve as Vehicles for Showcasing New Methodologies for Molecular Assembly

“…Zhou has described [ 90 ] an asymmetric hydrogenation process, using a homochiral iridium catalyst, that allows for the direct conversion of enones such as, for example, (±)- 136 into (–)-crinine [(–)- 26 ] and (+)- epi -crinine [(+)- 135 ] ( Scheme 45 ), each of which was obtained in good enantiomeric excess. These products were most readily obtained in pure form by conversion into their respective benzoyl esters, chromatographic separation of these, and subsequent independant saponification of each.…”

A Review on Recent Syntheses of Amaryllidaceae Alkaloids and Isocarbostyrils (Time period mid-2016 to 2017)

“…Through an analogous set of reactions used for conversion of 93 into 44 illustrated in Scheme 14, ketone 94 was converted into (+)-4a-dehydroxycrinamabine 95 in 20% yield (for 5 steps), the final one being treatment with concentrated hydrochloric acid in methanol (Scheme 15). iv) Bioinspired enantioselective synthesis of crinine-type alkaloids via iridium-catalyzed asymmetric hydrogenation of enones, by Zhou and co-workers: Zhou and co-workers developed an interesting iridium catalyst viz., Ir-SpiroPAP and applied it for the bioinspired asymmetric hydrogenation of racemic oxocrinine to produce the cis and trans products 96 and 97 (Scheme 16) [24]. These compounds were then converted into their benzoyl esters in order to simplify their chromatographic separation after which hydrolysis of the pure isolates afforded (-)-crinine 96 and (+)epivittatine 97.…”