Amides from boranes

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. 

Conversion to benzazepine was achieved under acidic conditions via hydrogenation in alcoholic solvents to form 25, which did not require isolation. Intermediate 25 was directly cyclized under basic conditions to give crystalline lactam 26. The base-mediated ring closure proceeded from the cis/trans mixture of 25 by epimerization of the benzylic methine permitting formation of the cyclic amide from the cis isomer. Finally, conversion of 26 to the desired benzazepine (8) was accomplished by in situ borane reduction and 8 was isolated as the tosylate salt in 81% yield. 

The other alkylborohydrides, 9-BBN and Sia2BH, also transform tertiary amides to alcohols [BK5, PSl]. Alcohols are obtained via the action of LiBH4 in MeOH-hot diglyme on some tertiary amides [S03] or by the controlled reduction with Li pyrrolidinoborohydride in THF [FFl] (Figure 3.69). This latter method, however, has some limitations. The reduction of 3.183 by Li pyrrolidinoborohydride or better by LiNH2BH3 obtained from borane ammonia and n-BuLi does not promote any racemization [MY2, MY4] (Figure 3.69). 

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. 

Without additional reagents Reactions with tris(dialkylamino)boranes Carboxylic acid amides from carboxylic acids Enamines from ketones... 

The aldol methodology was applied to the synthesis of FK-5067 Treatment of aldehyde 20 with cyclic borane 21 afforded homoallylic alcohol 22 in 17 1 diastereoselectivity (eq 8). Borane 21 was prepared from the reaction of (5, -1 with 2-acetoxyallyltri-7 butylstannane in CH2CI2 for 5 min at -78 °C, and then at 23 °C for 1.5 h. Reaction of the CH2CI2 solution in situ with aldehyde 20 at -78 °C for 1 h produced homoaUylic alcohol 22 as the major product. The bis(tosyl)amide from which reagent 21 was derived was efficiently recovered for reuse. 

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. 

This topological rule readily explained the reaction product 211 (>90% stereoselectivity) of open-chain nitroolefins 209 with open-chain enamines 210. Seebach and Golinski have further pointed out that several condensation reactions can also be rationalized by using this approach (a) cyclopropane formation from olefin and carbene, (b) Wittig reaction with aldehydes yielding cis olefins, (c) trans-dialkyl oxirane from alkylidene triphenylarsane and aldehydes, (d) ketenes and cyclopentadiene 2+2-addition, le) (E)-silyl-nitronate and aldehydes, (f) syn and anti-Li and B-enolates of ketones, esters, amides and aldehydes, (g) Z-allylboranes and aldehydes, (h) E-alkyl-borane or E-allylchromium derivatives and aldehydes, (i) enamine from cyclohexanone and cinnamic aldehyde, (j) E-enamines and E-nitroolefins and finally, (k) enamines from cycloalkanones and styryl sulfone. 

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... 

Earlier work2e by Miller and Chamberlin had already shown that borane-dimethyl sulfide was the reagent of choice for deoxygenating the amide of 13. The final step of the synthesis was O-debenzylation by catalytic hydrogenation. Note how the addition of acid helped prevent the catalyst from getting poisoned by the amine, ensuring that deprotection was rapid and efficient. 

Tris(organoamino)boranes have been utilized to prepare, in reasonable yields,4,5 mono- and dihalo(organoamino)boranes which are often difficult to obtain by direct amination of the boron trihalides. Carboxylic acids, 1,3-diketones, ketones, and /3-ketoesters have been converted into carboxamides, enamino-ketones, enamines, and j -enamino-amides, respectively, by reaction with an appropriate tris(organoamino)borane under very mild conditions.6 Sulfenamides (R2NSC6H5) have also been prepared in high yield from selected tris(organoamino)boranes and sulfenic esters under relatively mild conditions.7... 

A further method for the synthesis of the title compounds with only hydrogen as byproduct is the base-catalyzed dehydrogenative coupling (index D) of ammonia and tris(hydridosilylethyl)boranes, B[C2H4Si(R)H2]3 (R = H, CH3). Initially, the strong base, e.g. n-butyl lithium, deprotonates ammonia. The highly nucleophilic amide replaces a silicon-bonded hydride to form a silylamine and lithium hydride, which then deprotonates ammonia, resuming the catalytic cycle. Under the conditions used, silylamines are not stable and by elimination of ammonia, polysilazane frameworks form. In addition, compounds B[C2l-L Si(R)H2]3 can be obtained from vinylsilanes, H2C=CHSi(R)H2 (R - H, CH3), and borane dimethylsulfide. 

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