Sodium borohydride amide reactions with

Sodium borohydride in combination with ethanedithiol (but not ethanethiol) or with thiophenol reduces amides to amines in refluxing THF. The reaction proceeds most readily with primary amides tertiary amides are not reduced to any appreciable extent. Phthalimide (7) is reduced to (8). ... 

Alkylation of enamines with epoxides or acetoxybromoalkanes provided intermediates for cyclic enol ethers (668) and branched chain sugars were obtained by enamine alkylation (669). Sodium enolates of vinylogous amides underwent carbon and nitrogen methylation (570), while vicinal endiamines formed bis-quaternary amonium salts (647). Reactions of enamines with a cyclopropenyl cation gave alkylated imonium products (57/), and 2-benzylidene-3-methylbenzothiazoline was shown to undergo enamine alkylation and acylation (572). A cyclic enamine was alkylated with methylbromoacetate and the product reduced with sodium borohydride to the key intermediate in a synthesis of the quebrachamine skeleton (57i). 

Similarly to 8-lactone 260, y-lactone 263, prepared also from ( )-norcamphor (228), proved to be another useful intermediate for the synthesis of all four corynantheidol stereoisomers as well as of the corresponding 18,19-didehydro derivatives. Cleavage of the a-diketone monothioketal moiety in 263 and the formation of amide 265 by its reaction with tryptamine, followed by Bischler-Napieralski cyclization and sodium borohydride reduction, resulted in a mixture... 

Two years later, the same group reported a formal synthesis of ellipticine (228) using 6-benzyl-6H-pyrido[4,3-f>]carbazole-5,ll-quinone (6-benzylellipticine quinone) (1241) as intermediate (716). The optimized conditions, reaction of 1.2 equivalents of 3-bromo-4-lithiopyridine (1238) with M-benzylindole-2,3-dicarboxylic anhydride (852) at —96°C, led regioselectively to the 2-acylindole-3-carboxylic acid 1233 in 42% yield. Compound 1233 was converted to the corresponding amide 1239 by treatment with oxalyl chloride, followed by diethylamine. The ketone 1239 was reduced to the corresponding alcohol 1240 by reaction with sodium borohydride. Reaction of the alcohol 1240 with f-butyllithium led to the desired 6-benzylellipticine quinone (1241), along with a debrominated alcohol 1242, in 40% and 19% yield, respectively. 6-Benzylellipticine quinone (1241) was transformed to 6-benzylellipticine (1243) in 38% yield by treatment with methyllithium, then hydroiodic acid, followed... 

The use of activated anthranihc acid derivatives facUitates the preparation of the amides in those cases where the amines are either umeactive or difficult to obtain. Thus, reaction of (87-1) with phosgene gives the reactive the isatoic anhydride (89-1). Condensation of that with ortho-toluidine leads to the acylation product (89-2) formed with a simultaneous loss of carbon dioxide. This is then converted to the quinazolone (89-3) by heating with acetic anhydride. Reaction with sodium borohydride in the presence of aluminum chloride selectively reduces the double bond to yield the diuretic agent metolazone (89-4) [99]. 

Dihydrothieno[2,3-6][l,5]benzothiazepines (42) were synthesized from 2-(2-thienylthio)aniline (40). Compound 40 was acylated by treatment with acetic anhydride or benzoyl chloride to give N-acyl derivatives (41), which afforded compounds 42 by cyclization with phosphorus oxychloride and subsequent reduction with sodium borohydride or Zn/HCl. N-Dimethylaminopropyl derivatives 43 were prepared by reaction with di-methylaminopropyl chloride in the presence of sodium amide (Scheme 13) (67CZP124935 68CCC1846). 

Mechanisms of sodium borohydride reactions with primary, secondary, and tertiary amides have been investigated both at the B3LYP/6-31+- -G(d,p)//B3LYP/6-31G(d,p) and B3LYP/6-31++G(d,p)//HF/6-31G(d,p) levels of theory. The predicted structures of the key intermediates were then confirmed by experiment.317 For chemoselective reductions of a-substituted and aromatic esters with sodium borohydride, agreement between experimental results and theoretical computations at the B3LYP/6-31+-1-G(d,p)//HF/6-31G(d,p) levels of theory have been reported.318... 

In preparation for the eventual removal of the undesired oxygen function at C-10 of 313 via a Birch reduction, the phenol 313 was phosphorylated with diethyl phosphorochloridate in the presence of triethylamine to give 314, which underwent stereoselective reduction with sodium borohydride with concomitant N-deacylation to deliver the amino alcohol 315. N-Methylation of 315 by the Eschweiler-Clarke protocol using formaldehyde and formic acid followed by ammonolysis of the ester group and acetylation of the C-2 hydroxyl function afforded 316. Dehydration of the amide moiety in 316 with phosphorus oxychloride and subsequent reaction of the resulting amino nitrile 317 with LiAlH4 furnished 318, which underwent reduction with sodium in liquid ammonia to provide unnatural (+)-galanthamine. 

An alternative route (Scheme 48) was used by Dolby et al. (160) to prepare the tricyclic enamine (225). A Vilsmeier reaction between 3,4-methylenedioxy-A yV-dimethylbenzamidc (232), and pyrrole gave the amide (233) in 80% yield. Reduction with sodium borohydride provided the benzyl pyrrole (234), which... 

The reagent is prepared by reaction or toluene with hexane, ng agent comparable to other lithium VC 1,2-rcduction of enoncs. Reduction proceeds at —78°. However, ketones cr. Esters arc reduced to a mixture of in alcohol can be effected by reduction sodium borohydride. Tertiary amides Ics in generally high yield. Selective ondary halides is possible. 

Pictet-Spengler cyclization of L-tryptophan with formaldehyde afforded the monochiral carboxylic acids 20a,b, whereas cyclization with acetaldehyde yielded the diastereomeric carboxylic acids 21a,b (23). Acids 20a,b with a hydrogen at C-1 are enantiomers, but acids 21a,b are diaste-reomers the cis isomer 21a was the major reaction product when the cyclization of L-tryptophan with acetaldehyde was carried out in the presence of sulfuric acid. Direct removal of the carboxy group in these acids is difficult, but it can be accomplished in several steps dehydration of the amides prepared from the acids with phosphorus oxychloride affords nitriles, and the nitrile group can be removed by reduction with sodium borohydride in pyridine-ethanol (31). 

The structures of all currently approved gastric acid secretion inhibitors that act as inhibitors of the sodium-potassium pump consists of variously substituted pyiidylsulfonyl-benzimidazoles. A structurally very distinct compound based on a pyrimidine moiety has much the same activity as the benzimidazole-based drugs. In yet another convergent synthesis, reaction of (3-phenethylamine (53) with acetic anhydride affords amide 54. Treatment with polyphosphoric acid (PPA) then leads to ring closure to form the dihydroisoquinoline (55). Sodium borohydride then reduces the enamine function to afford fragment 56. 

Amidals 1 were prepared by the reaction of secondary allylic alcohols with benzyl hydroxy-methylcarbamate in dichloromethane using 4-methylbenzenesulfonic acid as a catalyst. The cyclization proceeded by treating 1 with mercury(II) acetate (1.25-2.0 equiv) in acetonitrile at 20 °C for 12 hours, followed by addition of sodium acetate and sodium borohydride to give the corresponding oxazolidine 2 in 60-90% yield158. 

The mercury-induced cyclization of amidals in which a stereogenic center is positioned at the amidal center adjacent to the nucleophilic amide functionality, gave oxazolidines with high stereoselectivity. Reaction of the amidals 10 with mercury(ll) acetate/mercury(ll) trifluoroac-etate in acetonitrile in the presence of sodium hydrogen carbonate followed by reductive cleavage with sodium borohydride afforded the corresponding fused oxazolidines 11164. 

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