Borane amide reductions

Scheme 26 Supposed mechanism of amide reduction by BH3 and subsequent hberation of the resulting amino-borane complex [30]...

The chemistry and procedures for modification of the - CO2H groups of PAA hyperbranched grafts on PE powder were analogous to those used for PAA grafts on PE or PP films and wafers. For example, a 90% yield in ester formation was possible using acid-catalyzed Fisher esterification. Likewise, quantitative reduction (ethyl chloroformate activation, borane-dimethyl sulfide reduction) to hyperbranched poly(allyl alcohol)s and amidation all could be carried out using procedures like those used for PAA/Au surfaces. 

High yields of amines have also been obtained by reduction of amides with an excess of magnesium aluminum hydride (yield 100%) [577], with lithium trimethoxyaluminohydride at 25° (yield 83%) [94] with sodium bis(2-methoxy-ethoxy)aluminum hydride at 80° (yield 84.5%) [544], with alane in tetra-hydrofuran at 0-25° (isolated yields 46-93%) [994, 1117], with sodium boro-hydride and triethoxyoxonium fluoroborates at room temperature (yields 81-94%) [1121], with sodium borohydride in the presence of acetic or trifluoroacetic acid on refluxing (yields 20-92.5%) [1118], with borane in tetrahydrofuran on refluxing (isolated yields 79-84%) [1119], with borane-dimethyl sulflde complex (5 mol) in tetrahydrofuran on refluxing (isolated yields 37-89%) [1064], and by electrolysis in dilute sulfuric acid at 5° using a lead cathode (yields 63-76%) [1120]. 

Introduction of the C2 sulfonamide is accomplished via sulfonylation with chlorosulfonic acid, conversion to the sulfonyl chloride using thionyl chloride, and amidation using concentrated ammonium hydroxide in tetrahydrofuran. Reduction of the 4-acetamido compound using borane-tetrahydrofuran complex provides the 4-ethylamino derivative. The 45,65-frans diastereomer is selectively crystallized as its maleate salt from acetone in the presence of the unwanted 4R,6S-cis diastereomer. Neutralization of the maleate salt and extraction of the free base in ethyl acetate, followed by formation of the hydrochloride salt, yields crude dorzolamide hydrochloride. 

A more recent example, which involves an enantiomerically pure compound, reverts to the original lead by incorporating a hydroxyl group on the benzylic carbon. Preparation of this close relative of ibutilide (5-3) uses the same starting material. Acylation of w-dibutylamine with the acid chloride from the treatment of (6-1) with tert-butylcarbonyloxy chloride leads to the amide (6-2). Reduction of the carbonyl group in this compound with chloro-(+)-diisopropylcamphemyl borane (DIPCl) proceeds to afford the R alcohol (6-3) in high enantiomeric exess. 

The facile reduction of amides by borane[67 69 was used for the reduction of the carbonyl group of the peptide bond.159 This reduction procedure is compatible with Boc, Z, OMe, and OBzl protecting groups. Generally, yields are relatively low. The following experimental procedure describing a dipeptide reduction, is the one which produces the best results/57 ... 

Polystyrene-bound amides, including peptides, can be reduced to the corresponding amines by treatment with borane in ethereal solvents. Other reagents, such as lithium aluminum hydride, are less convenient for reductions on insoluble supports, because insoluble precipitates can readily form and clog frits. Carbamates, tert-butyl ethers or thioethers, and trityl or benzhydryl amines remain unchanged upon treatment with borane, but carboxylic esters may undergo partial or complete reduction [178],... 

The reduction of amides with borane leads to the formation of borane-amine adducts, which can be resistant towards acylating agents or hydrolysis. Such borane complexes can be cleaved either by treatment with a secondary amine (e.g. piperidine, 60 °C [180]), or oxidatively, by treatment with iodine (Entry 3, Table 10.11 [181,182]). 

Reduction of amides. Sodium borohydride combined with methanesulfonic acid in DMSO reduces amides to the corresponding amines in 60-90% isolated yield. I he system also reduces acids and esters to primary alcohols. These reductions have been conducted with lithium aluminum hydride and with borane-tetrahydrofurane (5,48),2 hut with somewhat different selectivities. This new reagent, however, appears to be less hazardous than the latter reagent. 

Related catalysts for asymmetric borane reduction of ketones are open chain and cyclic phosphoric amides, in the oxidation state +3 or +5 (Scheme 11.3) [10, 11]. Early examples are the phosphonamides and phosphinamides 5a and 5b of Wills et al. [12] and the oxazaphospholidine-borane complex 6a of Buono et al. [13]. In the presence of 2-10 mol% catalysts 5a,b, co-chloroacetophenone was reduced by BH3 SMe2 with 35-46% ee [12]. For catalyst 6a a remarkable 92% ee was reported for the catalytic reduction of methyl iso-butyl ketone and 75% ee for acetophenone... 

Phosphoric amide catalysts for the borane reduction of ketones ... 

Reductive removal of the amide carbonyl with borane and Mannich closure of the middle ring give P-lycorane 72. A feature of this synthesis is that by changing the order of events and by adding ArLi with chelation control, all three lycoranes can be made selectively. 

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