Amides with borane

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]). 

The synthesis of the fluoroketone that combines the retroamide type bond (76) is shown in Scheme 5. The 2,2-difluoro-3-hydroxyester 11 from a Reformatsky reaction was converted to the primary amide 12 by treatment with ammonia in diethyl ether. Reduction of the amide with borane dimethyl sulfide and protection of the resulting amine gave the protected intermediate 13. For the preparation of peptides XIV and XV, the hydroxy function was oxidized to the corresponding ketone using pyridinium dichromate. 

The reduction of tertiary amides with borane-THF proceeds to give amines and with disiamylborane affords aldehydes. Consequently, it is possible to get the desired product using the appropriate reagent (Chart 25.1). 

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]. 

The amidic group in methyl A -acetyl-p-aminobenzoate was reduced preferentially to an ester group with borane in tetrahydrofuran (1.5-1.8 mol per mol of the amide), giving 66% yield of methyl p-A -ethylaminobenzoate. Similarly l-benzyl-3-methoxycarbonyl-5-pyrrolidone afforded methyl l-ben2yl-3-pyr-rolidinecarboxylate in 54% yield and l,2-diethyl-5-ethoxycarbonyl-3-pyra-zolidone gave ethyl l,2-diethylpyrazolidine-3-carboxylate in 60% yield. 

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],... 

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. 

A Princeton group announced the first synthesis of L-5-deazaFA (91) via a path which to date remains the shortest and most direct route to this series [79, 80], In one step, reaction of 2,4-diamino-6-hydroxypyrimidine (87a) with purified triformylmethane [81a,b] produced 2-amino-5-deazapterin-6-carbox-aldehyde (88a), which was characterized as the acetamide (89a). Reaction of (89a) with dimethyl p-aminobenzoyl-L-glutamate in glacial HOAc afforded an intermediate imine which was reduced in situ with borane-triethylamine, yielding (90). Saponification of the amide and esters then completed the synthesis of (91) in 62% yield from (88a) (Scheme 3.18). Adaptation of this... 

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. 

A series of 12- to 15-membered C-substituted cycles was prepared according to Scheme 12. Amide-benzylimines 70 were reductively coupled to the cycles 71 in a moderate yields and the cyclic amides were reduced with borane to give the free amines 72 <1995JOC3980>. Similarly, some other C-substituted derivatives were obtained <1995JOC3980>. 

Nitro-4-(trifluoromethyl)-phenol 42 (Scheme 17) in reaction with 2-bromo-2-methyl-propionamide in the presence of cesium carbonate and cesium iodide in acetonitrile afforded 2-hydroxy-2-methylpropionamide 43, apparently via derivative 44 as the intermediate [32]. Amide 44, prepared on a circuitous route, on reduction with borane-dimethylsulfide complex, gave amine 45 as the only isolated product. The parent 2-hydroxy-2-methyl-W-(2-... 

The reduction of amides to amines may be achieved with lithium aluminium hydride and with borane (Scheme 3.73). 

Reduction of pseudoephedrine amides with metal amide-borane complexes, and lithium amidotrihydroborate (LAB) in particular, furnishes the corresponding primary alcohols in high yield. In the initial report, LAB was prepared by deprotonation of the commercial, solid reagent borane-ammonia complex, using slightly less than 1 equiv of butyllithium as base (eq 11). In... 

HEXAHYDROCRESOL (25639-42-3) C,HuO Combustible liquid (flash point 149°F/65°C Fire Rating 2). Strong oxidizers may cause fire and explosions. Reacts with boranes, alkalis, aliphatic amines, amides, nitric acid, sulfuric acid. Attacks some plastics, rubber, and coatings. On small fires, use dry chemical powder... 

DINITROPHENOL (329-71-5) Combustible solid (flash point unknown). Contact with alkaline materials or UVlight may cause decomposition. Reacts with strong oxidizers, with a risk of fire or explosions. Incompatible with boranes, caustics, aliphatic amines, amides, isocyanates, nitric acid, sulfuric acid. 

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