Vitamin Reformatsky reaction

A new preparation of the C g ketone, an important synthon for the synthesis of vitamin A had also been published by Valla et al. [71]. Hence p-ionone and acetonitrile were condensed in the presence of KOH, to afford the nitrile (80%, E/Z isomers 80/20). A Reformatsky reaction of ethyl bromoacetate with the nitrile provided the ethyl P-ionylideneacetoacetate in 70% yield. Subsequent reduction with NaBH4, followed by esterification (MeSC Cl) and desulfonation of the unstable... 

The Reformatsky reaction of 4-bromocrotonate esters with conjugated enones can conceivably give four regioisomers, as shown in equation (27). Several workers have applied such reactions to the synthesis of vitamin A and related compounds. In most cases, 8-lactones derived from 1,2-7-adducts were obtained, as exemplified by results with -cyclocitral (equation 28). ... 

Reformatsky reactions have been used in the total synthesis of various important natural products such as phytol,225 naturally occurring polyenes,226 and vitamin A (from / -ionylideneacetaldehyde).227... 

Of the various organometallic reactions employed in carbon-carbon bond formation, the metal acetylide, Grignard, and Reformatsky reactions have been the most prevalent in the synthesis of vitamin A (7) and carotenoids [1]. However, there has been considerable interest in the applications of transition metals and, for the preparation of symmetrical carotenoids, low valent titanium. This article is divided according to the metals used in carbon-carbon bond formation, with further subdivisions based on reaction type and/or putative reactive intermediates. For multi-step syntheses, only the steps that employ metals in carbon-carbon bond formation are discussed and, whenever possible, the reaction conditions and yields are indicated on the reaction schemes. 

Carbon-14-labeled TMS acetates are most directly prepared from the corresponding haloacetates, as preparation by the reaction of lithiated acetate esters with trimethylsilyl chloride (TMSCl) would result in a mixture of C- and O-silylated products. The preferred procedme involves reaction of TMSCl with the organozinc reagent of the haloacetate in a modified Reformatsky reaction. An application of this Peterson-olefination sequence is illustrated by the preparation of the antipsoriatic vitamin D derivative 204. Reaction of the anion of benzyl trimethylsilyl[l, 2-"C2]acetate (20ft) with TBS-protected cyclohexa-none-3,5-diol afforded the expected benzyl cyclohexylidene[l,2-"C2]acetate t201i in moderate yield. The subsequent transformation of 201 to the phosphine oxide 202 followed... 

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