Issue in Honor of Prof. Binne Zwanenburg ARKIVOC 2004 (ii) 24-50
respectively. Treatment of the unsaturated ammonium salt 20 with KOH,44 t-BuOK,45,46 NaOH,47,48 NaOMe,49 or Et3N,50 gave products which immediately decomposed during the isolation process. Only when 20 was treated with LDA the desired product 21 together with the N-monomethylated product 19 could be isolated in 32% and 26% yield, respectively (Scheme 5). The formation of demethylated products can be explained by difficulties in the proton abstraction, which is necessary for ringopening. In these cases the competitive nucleophilic substitution resulting in demethylation is strongly favored over the Hofmann degradation. LDA is a small and strong enough base to abstract the proton from C20, but only in the case of 20 compound 21 was formed. The presence of the .16,17 double bond makes H20 to an allylic proton, which is more prone to abstraction. The further degradation of 21 to DPA (6) requires several protection and deprotection steps as shown by Maitra and Breslow,51 which are not very attractive for industrial application. Besides the use of several hazardous reagents is another reason to look for alternatives.
The spirosolane routes
H N H 11 a 12 b 15 c OH d H HO 22
H HO N HH OH Cl HO HH e O NH fH 23
24
25 Scheme 6. a. BrCN, CHCl3, ., 24 h, 68%. b. KOAc, DMF, 83%. c. Red-Al, toluene, ., 93%. d. NCS, CH2Cl2, RT, 2 h, 95%. e. NaOMe, MeOH, ., 95%. f. Ac2O, pyridine, 98%. g. HOAc, ., 85%. h. CrO3, HOAc, ., 76%.
AcO 6hg O AcO HH O N H H O NHAc ISSN 1424-6376 Page 31 ©ARKAT USA, Inc
