Phthalimides sodium borohydride

Amines f-Butyl benzotriazol-1-yl carbonate. r-Butyl 2-pyridyl carbonate. N-(Ethoxycar-bonyl)phthalimide. 2-(2-Pyridyl)ethyl-p-ni-trophenyl carbonate Sodium borohydride. 

R = COzMe, COzEt), in water to yield the benzoic acid 179 (R = CO2H), and in alcoholic solutions containing dimethylamine or pyrrolidine to afford benzamides 179 [R = CONMe2, CON(CH2)4]. Sodium borohydride reduction of 127 afforded the benzyl alcohol 179 (R = CH2OH) and phthalimide... 

Alternative methods to remove the phthaloyl group have been developed over the years as the classical method is often deemed too harsh, sometimes leading to degradation of other functionalities present. An example is the two-stage one-pot method using sodium borohydride followed by acetic acid reported by Ganem and co-workers.8 Previously, NaBH4 reduction of phthalimides has been described but these examples... 

Theil et al. developed a method for chemoenzymatic synthesis of both enantiomers of cispentacin [89]. frans-2-Hydroxymethylcyclopentanol, obtained by the sodium borohydride reduction of ethyl 2-oxocyclopentanecarboxylate, was monosilylated with tert-butyldimethylsilyl (TBDMS) chloride to afford 55. Lipase PS-catalysed transesterification with vinyl acetate in /erf-butyl methyl ether furnished the ester 56 and the alcohol 57. The deacetylated 58 was obtained by the Mitsunobu reaction with phthalimide, triphenylphosphine and diethyl azodicarboxylate (DEAD) to furnish the cis oriented 59 with inversion of configuration (not retention as mentioned in the original article) (Scheme 9). Desilylation, Jones oxidation and subsequent deprotection with aqueous methylamine gave the ( R,2S) enantiomer 5 [89]. The (15, 2/f) enantiomer was prepared by the same route from the silyl alcohol 57. 

Sodium borohydride in combination with ethanedithiol (but not ethanethiol) or with thiophenol reduces amides to amines in refluxing THF. The reaction proceeds most readily with primary amides tertiary amides are not reduced to any appreciable extent. Phthalimide (7) is reduced to (8). ... 

Isomannide (80) was the core for a hexahydrofurofuran library." Primary amines were loaded onto solid-support by reductive amination and acylated with bromoacetic acid to give bromides 79 (Scheme 7.16). Alkylation of bromides 79 on solid-support with isomannide (80) gave the solid-supported alcohols 81. A Mitsunobu reaction with phthalimide (82) proceeded to furnish amines 83 in excellent yield and purity after removal of the protecting group." " Support-bound primary amines 83 were converted to secondary amines by stepwise imine formation with aldehydes 84 and reduction with sodium borohydride." The hindered secondary amines 85 were acylated with acid chlorides, sulfonyl chlorides, isocyanates, and isothiocyanates to yield 87 after cleavage from solid-support. 

T. Watanabe, F. Hamaguchi, and S. Ohki. Reduction of cyclic imides. II. Reduction of 3- and 4-substitutkl phthalimides with sodium borohydride. Chem. and Pharm, Bull. Japan), 1978, 26, 530. 

SO an excess is used to minimize this. A secondary or tertiary amine may be prepared by treating a primary or secondary amine with an alkyl halide or sulfonate in the same way. Primary amines can be made cleanly using potassium phthalimide instead of ammonia, and a number of improvements to the original procedure have been suggested. Osby and co-workers have treated the phthalimide with sodium borohydride and propanol followed by acetic acid to isolate the primary amine in high yield [92]. 

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