Amines with borane

The desired pyridylamine was obtained in 69 % overall yield by monomethylation of 2-(aminomethyl)pyridine following a literature procedure (Scheme 4.14). First amine 4.48 was converted into formamide 4.49, through reaction with the in situ prepared mixed anhydride of acetic acid and formic acid. Reduction of 4.49 with borane dimethyl sulfide complex produced diamine 4.50. This compound could be used successfully in the Mannich reaction with 4.39, affording crude 4.51 in 92 % yield (Scheme 4.15). Analogous to 4.44, 4.51 also coordinates to copper(II) in water, as indicated by a shift of the UV-absorption maximum from 296 nm to 308 nm. 

A number of less hindered monoalkylboranes is available by indirect methods, eg, by treatment of a thexylborane—amine complex with an olefin (69), the reduction of monohalogenoboranes or esters of boronic acids with metal hydrides (70—72), the redistribution of dialkylboranes with borane (64) or the displacement of an alkene from a dialkylborane by the addition of a tertiary amine (73). To avoid redistribution, monoalkylboranes are best used /V situ or freshly prepared. However, they can be stored as monoalkylborohydrides or complexes with tertiary amines. The free monoalkylboranes can be hberated from these derivatives when required (69,74—76). Methylborane, a remarkably unhindered monoalkylborane, exhibits extraordinary hydroboration characteristics. It hydroborates hindered and even unhindered olefins to give sequentially alkylmethyl- and dialkylmethylboranes (77—80). 

Primary dialkylboranes react readily with most alkenes at ambient temperatures and dihydroborate terminal acetylenes. However, these unhindered dialkylboranes exist in equiUbtium with mono- and ttialkylboranes and cannot be prepared in a state of high purity by the reaction of two equivalents of an alkene with borane (35—38). Nevertheless, such mixtures can be used for hydroboration if the products are acceptable for further transformations or can be separated (90). When pure primary dialkylboranes are required they are best prepared by the reduction of dialkylhalogenoboranes with metal hydrides (91—93). To avoid redistribution they must be used immediately or be stabilized as amine complexes or converted into dialkylborohydtides. 

IV-substituted and B-substituted borazines are readily prepared by suitable choice of amine and borane starting materials or by subsequent reaction of other borazines with Grignard reagents, etc. Thermolysis of monocyclic borazines leads to polymeric materials and to polyborazine analogues of naphthalene, biphenyl, etc. ... 

Oximes are generally reduced to amines (19-44), ° but simple reduction to give hydroxylamines can be accomplished with borane or sodium cyanoborohy-dride. ... 

On the theoretical side, study of the dissociation of addition compounds of amines with trimethylborane, boron trifluoride, and borane provide a new quantitative approach to steric strains. These studies quickly removed doubts as to the importance of steric effects in chemical behavior. 

The Leuckart-Wallach reaction is the oldest method of reductive amination of carbonyl compounds. It makes use of formamide, formic acid or ammonium formate at high temperature. The final product is a formamide derivative, which can be converted to an amine by reduction or hydrolysis. The method has been applied to the preparation of 1,2-diamines with a norbornane framework, which are interesting rigid analogues of 1,2-diaminocyclohexanes. As a matter of fact, starting from N-acetyl-2-oxo-l-norbornylamine 222, the diamide 223 was obtained with excellent diastereoselectivity and then converted to the M-methyl-N -ethyl derivative 224 by reduction with borane [ 104] (Scheme 34). On the other hand, when the reac-... 

Tertiary amines have been prepared in good yield by a repetitive generation of imida-zolides and subsequent reduction with borane/dimethylsulfide, 1361 as the following examples show ... 

Reaction of the salts of primary and secondary alky Initio compounds with diborane in THF solution at 25 °C yields the corresponding hydroxylamines.117 Kabalka has reported the reduction of nitroalkenes to hydroxylamines or amines with a variety of borane and borohydride reagents (Eq. 6.61).118... 

XII), which is then reduced with borane in THF to produce (VI). The trimethoxy secondary amine (VI) is demethylated by refluxing its solution in glacial acetic acid and HBr to yield dobutamine hydrobromide... 

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 N-N bond of polystyrene-bound hydrazines, which are prepared by reaction of organolithium compounds with resin-bound hydrazones [457], can be cleaved by treatment with borane to yield a-branched, primary amines (Entry 9, Table 3.23). An additional example of reductive cleavage to yield amines is shown in Entry 10 (Table 3.23), in which a resin-bound a,a-disubstituted nitroacetic ester undergoes decarboxylation and reduction to the primary amine upon treatment with lithium aluminum hydride. 

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]). 

Few examples of the preparation of hydrazines or hydroxylamines on insoluble supports have been reported (Table 10.17). Hydrazines have been prepared by the reduction of aromatic diazonium salts or /V-nitroso amines (prepared from secondary amines by treatment with tert-butyl nitrite [340]), and by the N-amination of support-bound amines (Entry 3, Table 10.17). The direct reduction of hydrazones with borane to yield hydrazines on solid phase has not been reported, and appears to be difficult because of the ease with which the N-N bond of hydrazines is cleaved by reducing agents [340]. 

Reduction of the nitro compounds (193 R = R = H, or R = Me, R = OH) with lithium aluminum hydride affords the corresponding saturated amine.556 Similar reduction of carboxamides with the general formula (194) affords the corresponding amines143,8n 313, 568,569. jn t,]ie Case of 194 (R = H, R = 6-OMe), reduction with borane tetrahydrofuranate is more satisfactory.312... 

The reaction of 154 with chloroacetonitrile in the presence of potassium /-butoxide afforded 155. The nitrile group was reduced with borane methyl sulfide to the corresponding amine 156, which on treatment with sodium methoxide was transformed into the 1,4-oxazepine 157 (Scheme 23) <1996JOC6060>. 

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. 

Aryl alkyl ketoxime ethers, Ar-C(R1)=N-OR2, have been reduced with borane-THF at ca 0 °C to give amines, Ar- CH(R )-NH2 88 A chiral BINAP with an O3BN (ee) framework gives up to 98% ee. 

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