Lithium aluminum hydride diastereoselective synthesis

Earlier in 2006, Bertrand and Wolfe reported on the synthesis of (-l-)-preussin starting from decanal 103 (Scheme 40.22). After seven steps, the key intermediate 108 was obtained in 97% ee and 30% overall yield. 108 underwent Pd-catalyzed C N alkylative cyclization to afford the pyrrolidine derivative 109 with excellent diastereoselectivity. Derivative 109 under lithium aluminum hydride (LAH) reduction followed by alkaline workup produced (+)-preussin 100 in excellent yield. 

The reaction between ethyl Hthiopropiolate and the N-acylpyridinium salt formed by reaction of 4-methoxy-3-methyl-5-(triisopropylsilyl)pyridine 2363 with (+)-frafis-2-(a-cumyl)-cyclohexyl chloroformate (TCC chloro-formate) was the starting point in the synthesis of (-l-)-aUopumihotoxin 267A (1718) by Comins et al. (Scheme 301). The dihydropyridone product (—)- 2364 was obtained diastereoselectively (>96%) before hydrogenation to the saturated ester (+)-2365. However, some epimerization of the methyl substituent was apparent after cleavage of the TCC carbamate with lithium methoxide and cyclization to the indolizidinone (—)-2366 (dr 8 1). Acetoxylation at C-8 with lead tetraacetate was stereoselective, and introduced the acetate from the axial direction, possibly by stereoelec-tronicaUy-controUed intramolecular transfer of acetate from a lead—enol intermediate. The acetoxy product (—)-2367 was protodesilylated with formic acid, after which a one-pot tandem reduction with K-Selectride followed by hthium aluminum hydride gave diol (- -)-2368 with complete... 

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