Crotyl acetal reduction

Coupling, reductive, of o-chlorobenzal-dehyde by hexamethylphosphor-ous triamide to give 2,2 -di-chloro-a,a -epoxybibenzyl, 46, 31, -Cresol, 48, 96 -t-Crotonolactone, 46,22 Crotyl diazoacetate, 49, 22, 24 Cupric acetate in coupling of phenyl-acetylene, 46, 39... 

Brown s crotylboration protocol was used effectively in the synthesis of azu-mamide A 28. Azumamides are unusual cyclic peptides that show potent inhibitory activity on histone deacetylase enzymes. A highly diastereo- and enan-tioselective (dr >99% 98% ee) crotylation of 3-benzyloxypropanal with the chiral reagent ( >crotyl-1Ipc2borane (l19E) afforded the homoallylic alcohol 29. Subsequent reductive ozonolysis and K2CO3-mediated hydrolysis of the acetate furnished the diol 3016 (Scheme 3.1m). 

Treatment of (31) with crotyl chloride-potassium carbonate in DMF afforded (33), which was converted into (34) by heating in a sealed tube. Methylation of the phenol (34) with methyl iodide-potassium carbonate gave (35). Osmic acid-sodium periodate oxidation produced the keto-aldehyde (36). Acetalization by standard methods gave the diacetal (37). Reduction of (37) with lithium in liquid ammonia and subsequent toluene-p-sulphonic acid work-up afforded (38) in a yield of 50 %. A vinylogous aldol condensation was effected with methan-olic potassium hydroxide. The resulting mixture was oxidized with chromium... 

The o, )-unsaturated ester 7 can be transformed reductively into the p,Y-unsaturated system 8 in high yield using magnesium in methanol J Reaction of the chiral crotyl silane 9 with various aldehydes and acetals offers a diastereoselective approach to branched P,Y-unsatuiated esters, as in the example in Scheme 2, and, as indicated, stereospecific allylic rearrangement gave the a,p-unsaturated system. Similar reactions were also described using the C-2 epimer of 9. ... 

Next, regioselective silyiation, reduction, and protection steps produced 288. Oxidative cleavage of C=C double bond and diastereoseiective crotylation with 290 gave intermediate 291. The latter was submitted to hydroformylation and acetate formation yielding product 292 (Scheme... 

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