Double Lawton S_N2‘Addition to Epoxyvinyl Sulfones:  Selective Construction of the Stereotetrads of Aplyronine A

Abstract

[reaction: see text] Enantiopure epoxyvinyl sulfones function as templates for the diastereoselective construction of the three stereotetrads of aplyronine A. Lawton S(N)2' addition of 3,5-dimethylpyrazole followed by its displacement in an alcohol-directed Lawton S(N)2' reaction establishes the required product stereochemistry with high selectivity.

Palladium-catalyzed formation of oxazolidinones from biscarbamates: a mechanistic study

“…Fiaud et al suggested an antiperiplanar orientation of metal and the nucleophile (–NHTs group) [6]. According to the S N 2' substitution reaction mechanism [27–30], nucleophiles attack the double bond from the same side from which the leaving group departs, as shown below (Fig. 3).…”

Recent Progress in The Synthetic Study of an Antitumor Marine Macrolide Aplyronine A and Related Molecules

“…28 They previously established the stereoselective synthesis of vinyl sulfone 56 as a starting material of the C15-C20 part ( Figure 5). 30 These vinyl sulfones 59 and 69 were used as precursors of C5-C11 and C21-C27 segments 62 and 73, respectively. 30 These vinyl sulfones 59 and 69 were used as precursors of C5-C11 and C21-C27 segments 62 and 73, respectively.…”

“…29 They also developed a stereoselective method of synthesizing seven-membered vinyl sulfones 59 and 69 involving four contiguous stereogenic centers by using the double Lawton SN2' addition as a key step. The seven-membered vinyl sulfone 69, 30 On the other hand, they synthesized the C15-C27 segment 75 by using Julia-Kocienski olefination 31 as a key step (Scheme 12).…”

“…Strategy for the synthesis of aplyronine A (1) developed by the Fuchs group Synthesis of the C15-C20 segment 58 is shown in Scheme 11. Synthesis of the C1-C20 segment 68 started from seven-membered vinyl sulfone 5930 (Scheme 11). Synthesis of the C1-C20 segment 68 started from seven-membered vinyl sulfone 5930 (Scheme 11).…”

Nucleophilic Aliphatic Substitution

“…32 can be methylated in a second regio-and stereo-specific S N 2 reaction with MeMgBr de (Scheme 12) to give >95% yield with 95% of (26) with the methyl group syn to the OH group. Surprisingly, when the temperature of the methylation was lowered to 0 • C, the syn:anti ratio decreased from 20:1 to 1:1 and it was reduced further to 1:4 at −45 • C. This temperature dependence was attributed to an equilibrium between two conformations of the magnesium alkoxide intermediates in the methylation reaction.…”