An Asymmetric Synthesis of Fully Functionalized B Ring System of Taxol

Abstract

Optically active 7-t-butyldimethylsiloxy-4,8-dibenzyloxy-6,6-dimethyl-5-p-methoxybenzyloxy-2-cycloocten-1-one (1) was synthesized from 3,7-dibenzyloxy-4,8-di-t-butyldimethylsiloxy-5,5-dimethyl-6-p-methoxybenzyloxy-2-octanone (2) by way of intramolecular Reformatsky-type reaction using SmI2.

Coupling of Organic Halides with Carbonyl Compounds Promoted by SmI2, the Kagan Reagent

“…Intramolecular versions of the SmI 2 mediated Reformatsky reaction work fine. Cyclization of α-chloro or bromo ketones bearing an aldehydo group in suitable position takes place efficiently and allows the synthesis of the fully functionalized eight-membered B ring system of Taxol (Scheme ) and of an 11-membered ketone precursor of the cytochalasin ring system (Scheme , entry b) . In the latter case, remarkably high stereocontrol has been achieved which is unavailable under usual conditions involving, for example, zinc (Scheme , entry a) …”

Progress in the Construction of Cyclooctanoid Systems: New Approaches and Applications to Natural Product Syntheses

“…Samarium iodide mediated Barbier/Grignard-type reactions have also been developed for the synthesis of eight-membered rings. , Inanaga et al . have reported the cyclization of bromoaldehyde 330 → 331 .…”

“…Shina et al . have converted the highly functionalized bromoaldehyde 332 → 333 representing the highly embellished ring B of taxanes, Scheme . Other interesting examples include cyclization of 334 → 335 and 336 → 337 .…”

“…Samarium iodide mediated Barbier/Grignard-type reactions have also been developed for the synthesis of eight-membered rings. 135,136 Inanaga et al 135 have reported the cyclization of bromoaldehyde 330 f 331. Shina et al 136 have converted the highly functionalized bromoaldehyde 332 f 333 representing the highly embellished ring B of taxanes, Scheme 66.…”

Asymmetric Total Synthesis of Taxol.

“…2). This novel strategy offers a flexible synthesis of the B ring system of Taxol and its analogues from chiral linear precursors,6), 7) Commercially available neopentyl glycol (1) was converted to aldehyde 2 via its benzylideneacetal. An asymmetric aldol reaction between 2 and the requisite ketene silyl acetal promoted by Sn(OTf)2 coordinated with chiral diamine gave the desired optically active ester 3 in good selectivity (anti/syn=79121, anti aldol; 93% ee).…”