Acyclic Stereoselection. 25. Stereoselective Synthesis of the C-1 to C-7 Moiety of Erythronolide A.

Article abstract of DOI:10.1021/jo00212a018

A stereoselective synthesis of aldehyde ester 1, a synthon for the C-1 to C-7 section of erythronolide A, is reported.The synthesis begins with β,γ-unsaturated aldehyde 12, which is prepared from mesityl oxide as shown in eq 2.Aldehyde 12 reacts with the preformed lithium enolates of reagents 13 and 5 to give, in each case, a 15:1 mixture of two aldols (eq 3 and 4).Reduction of the major isomer 16 from the reaction of 5 with lithium aluminum hydride followed by periodate cleavage of the resulting vicinal diol provides β-hydroxy aldehyde 20.This material is protected as triethylsilyl derivative 21, which is treated with the lithium enolate of BHT O-benzyllactate (22c).The resulting 5:1 mixture of aldols is converted into acetonides 27c and 28c, which are separated by chromatography.The stereostructure of the major acetonide 27c was elucidated by single-crystal X-ray analysis (Figure 1).Lithium aluminum hydride reduction of 27c gives alcohol 29, which is converted into acetate 34.Ozonolysis of this material gives aldehyde 35, which is oxidized by pyridinium dichromate in DMF.Diazomethane esterification provides diester 36, which is methanolized to hydroxy ester 37.Swern oxidation of 35 provides racemic ester aldehyde 1.Enantiomerically homogeneous 1 is obtained in similar sequence, via the O-methylmandelates 39a and 39b.