Boranes with amides

In the late 1960s, methods were developed for the synthesis of alkylated ketones, esters, and amides via the reaction of trialkyl-boranes with a-diazocarbonyl compounds (50,51), halogen-substituted enolates (52), and sulfur ylids (53) (eqs. [33]-[35]). Only one study has addressed the stereochemical aspects of these reactions in detail. Masamune (54) reported that diazoketones 56 (Ri = CH3, CH2Ph, Ph), upon reaction with tributylborane, afford almost exclusively the ( )-enolate, in qualitative agreement with an earlier report by Pasto (55). It was also found that E) - (Z)-enolate isomerization could be accomplished with a catalytic amount of lithium phenoxide (CgHg, 16 hr, 22°C) (54). 

SCHEME 18.30 Proposed mechanism of the n-BuLi catalyzed dehydrocoupling of tris(hydridosilyl-ethylene)boranes and ammonia. (1) deprotonation with formation of an amide, (2) substitution of silicon-bonded hydride with amide, (3) polymerization through condensation. 

The reduction of indoles by pyridine-borane in CF3COOH [K3] or BH3 THF in CF3COOH [MMl] is compatible with amide, nitrile, or ester groups. It is interesting to emphasize that LAH in ether media reduces these groups without affecting the... 

We wonld expect a considerable downfield shift npon coordination of the phosphane, and we are therefore not snrprised to observe it in the ensning adducts. However, why do we observe an npfield shift upon coordination to the borane with the phosphanes in the lower part of the table The difference mnst lie in the behavior of the snbstituents on phosphorns, as this is the one parameter that changes as we look down the list. In the top part, the snbstituents are H, methyl, and phenyl, whereas in the lower part, the snbstitnents are flnoride, amide, and methoxide. The latter three (F, NMe and MeO) are capable of a 7r-bonding interaction toward phosphorus that increases as the electron density on phosphorus diminishes upon coordination. Since the P-NMR chemical shifts are more sensitive toward. ir-interactions than cr-interactions, the net result can very well be an upfield shift upon coordination of the phosphane, if substituents capable of . r-backbonding are present on phosphorus. 

Starting from a vinyl-substimted resin, hydroboration with 9-BBN yields a homobenzylb-orane (Scheme 9). This intermediate can be coupled with various functionalized aryl iodides as well as vinyl and alkyl iodides giving rise to resins with amide, ester, or protected hydroxy functionaUties.t Similarly, bromostyrene could be coupled with functionalized boranes for the attachment of preformed handles, for example, for the construction of the silicon traceless linker.t i The carbometaUation of certain alkenes such as tropanes and the subsequent treatment with aryl boronic acid gives rise to two new C—C bonds (Scheme 10). 

Amides are derivatives of carboxylic acids, so that their coordination behavior to boranes might be similar to that of their parent compounds. B-NMR spectroscopic studies have shown that compounds 31 and 32 are monomeric species in solution, while compounds 33 and 34 with the more Lewis acidic 9-borabicyclo[3.3.1]nonyl unit form aggregates that may be dimeric, oligomeric, or polymeric. The grade of association could not be determined by mass spectrometric analyses, because in all cases only the monomer is liberated into the gas phase [65]. 

By chance, the existence of the borane complex 330 of 329 was discovered. The liberation of 330 occurred with the best efficiency with sodium bis(trimethylsilyl)-amide from the borane complex 327 of 326. When styrene or furan was used as the solvent, three diastereomeric [2 + 2]-cycloadducts 328 and [4 + 2]-cycloadducts 331, respectively, were obtained in 30and 20% yield (Scheme 6.70) [156]. With no lone pair on the nitrogen atom, 330 cannot be polarized towards a zwitterionic structure, which is why its allene subunit, apart from the inductive effect of the nitrogen atom, resembles that of 1,2-cydohexadiene (6) and hence undergoes cycloaddition with activated alkenes. It is noted that the carbacephalosporin derivative 323 (Scheme 6.69) also does not have a lone pair on the nitrogen atom next to the allene system because of the amide resonance. 

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. 

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 ... 

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