Formal Total Synthesis of (+)‐Cortistatins A and J

Abstract

An efficient formal total synthesis of (+) cortistatins A and J has been accomplished, by exploiting a highly diastereoselective intramolecular [4+3] cycloaddition of epoxy enolsilanes as the key reaction to construct rings B and C of the cortistatins in one step.

Escaping from Flatland: Stereoconvergent Synthesis of Three‐Dimensional Scaffolds via Ruthenium(II)‐Catalyzed Noyori–Ikariya Transfer Hydrogenation

“…employed reductive desymmetrization of 2‐methyl‐2‐alyl‐cyclopentane‐1,3‐dione 126 as a first step in their formal total synthesis of cortastatins, for example 128 (Figure 30). [52] ( R , R )‐ H catalyzed transfer hydrogenation was reproducible on 15 to 42 g scale and afforded 127 in up to 95 % yield (a mixture of diastereomers) with excellent enantiomeric purity (>99 % ee ) and acceptable diastereoselectivity. The enantiopure desired diastereomer was isolated in 77 % yield after column chromatography as an oil.…”

Recent Advances in Reductive Desymmetrization of Diketones

“…This mini review has presented some efficient methods for catalytic reductive desymmetrization of achiral and meso substrates by enzyme, transition‐metal catalysis, organocatalysis, frustrated Lewis pairs catalysis and photoredox catalysis for nearly a decade (Table 1). They offered a straightforward and facile access to a wide range of chiral hydroxy ketones which were widespread in nature and considered as significant motifs in drugs owing to the pharmaceutical and biological activities [9,10,12,15,20] . The desymmetrization of diketones also provided a novel and highly efficient strategy for the construction of all carbon quaternary stereocenters and multiple stereogenic centers [9–13,15,18–23,25,27] …”

“…The ruthenium‐catalyzed hydrogenative desymmetrization of prochiral 1,3‐diketones with an α ‐ tertiary or quaternary carbon is probably one of the most streamlined reactions to construct β‐hydroxy ketone derivatives. The desymmetrization was applied to the synthesis of (+)‐cortistatin A and J by Chiu and co‐workers [20] in 2015. Substrate 2‐allyl‐2‐methylcyclopentane‐1,3‐dione 14 a in the presence of Noyori's Ru transfer hydrogenation catalyst was converted to the key intermediate β‐hydroxy ketone 15a′ on gram scale, the synthetic utility of which was demonstrated in the natural products synthesis (Scheme 12).…”

Total synthesis of cyrneines A–B and glaucopine C

“…Notably, the reaction was viable for 2-furyl and benzo-2-furyl boronic acids ( 17 f , 17j , 17n , 17r , and 17w ). These results would be appealing because coupling of 2-heteroaryl boronic acids is a considerable challenge resulting from the detrimental pyrolysis under conventional heating conditions 35 , especially with the nonactivated enol triflates as seen from the sporadic examples explored in the synthesis of relevant natural products 36 .…”