Acetamides, protecting groups

In a closely related example, a Mannich reaction of the somewhat more complex phenol (20-1) with formaldehyde and fert-butylamine gives the aminomethylated product (20-2). Hydrolysis of the acetamide protecting group then affords the corresponding aniline (20-3). Alkylation with the quinoline (17-6) in this case also proceeds on aniline nitrogen. The selectivity over the more basic secondary side nitrogen can probably be ascribed to steric hindrance about the latter. There is thus obtained tebuquine (20-4) [22]. 

Acetamide protecting group, 696, 697 Acetone in cyclization reactions, 78, 80. 85. 

The phosphitylation procedure activated by tetrazole led to the phosphite structure (step a) which was effectively oxidized by TBHP to yield the corresponding phosphate (step b). Finally all 2-cyanoethyl protecting group were removed by the action of DBU in the presence of the silylating reagent bis(trimethylsilyl)acetamide BSA (step c). The latter is indispensable to secure total deprotection. 

A convenient procedure for preparing dialkylphosphinic acids 62 involves addition of H-phosphinic acids and esters to conjugated double bonds via the silyl 87-89 or metal phos-phonite 61,[90 94] as illustrated in Scheme 21. The silyl phosphonite intermediates 61 (M = TMS) are typically formed either from phosphinic acids or esters using chlorotri-methylsilane or bis(trimethylsilyl)acetamide. The metal phosphonite intermediates 61 (Y = Li, Na, etc.) are prepared by deprotonation of the acids with a base such as sodium hydride, sodium methoxide, or lithium diisopropylamide. The conjugated double bonds are typically acrylic acids and esters substituted in the a-position with the appropriate amino acid side chain. After appropriate protecting group manipulations, additional amino acids... 

The first application of the AA process was the short and efficient synthesis of the paclitaxel (Taxol) side chain 32 (Scheme 4) [58]. The hydroxysulfonamide 31 crystallized directly from the reaction mixture (69% yield, 82% ee) and was transformed to 32 in two steps. The procedure was further improved when the acetamide-AA was discovered [22]. The hydroxyactamide 33 was easily obtained in good yield (71%) and excellent ee (99% ee) and removal of the N-protecting group was nearly quantitative. A direct benzamide-AA gave 34, the isopropyl ester of 32, in a single step, though with lower yield (46%) than the acetamide-AA [24]. 

This group was used as a bulky protective group to the intramolecular C-H insertion of a-diazo acetamides and in directed orthometalation reactions of aryl amides. The cumyl group is readily cleaved with CF3CO2H. Formic acid has also been used to remove a cumyl group. 

---