Sodium borohydride imines

Macrocycles have been prepared by formation of macrocyclic imines as well as by using variations of the Williamson ether synthesis ". Typically, a diamine or dialdehyde is treated with its counterpart to yield the Schiff s base. The saturated macrocycle may then be obtained by simple reduction, using sodium borohydride, for example. The cyclization may be metal-ion templated. In the special case of the all-nitrogen macrd-cycle, 15, the condensation of diamine with glyoxal shown in Eq. (4.14), was unsuccess-ful ... 

Condensation between aldehyde 40 and amine 29 followed by sodium borohydride reduction of the resultant imine and cyclisation yielded isoquinoline 41 in good yield. Cyclisation occurred exclusively at the more electron-rich aromatic group. 

Reduction of the imine with sodium borohydride leads to an intermediate amino-ester that cyclizes spontaneously to the <5-lactam function. Solvolysis of the acetyl group with methoxide followed by acylation of the hydroxyl group thus liberated with trimethoxybenzoyl chloride leads to 38. Bischler-Napieralski cyclodehydration (phosphorus oxychloride) effects closure of the remaining ring. Reduction of the imine thus formed with sodium borohydride gives 39. This, it should be noted, leads to the... 

This was converted to its imine with methylamine catalyzed by titanium tetrachloride and then sodium borohydride reduction produced 17 as a mixture of diastereomers. This was resolved by column chromatography to give sertraline [5]. Dextrorotatory cis sertraline is substantially more potent than its isomers. 

The synthesis of the E-ring intermediate 20 commences with the methyl ester of enantiomerically pure L-serine hydrochloride (22) (see Scheme 9). The primary amino group of 22 can be alkylated in a straightforward manner by treatment with acetaldehyde, followed by reduction of the intermediate imine with sodium borohydride (see 22 —> 51). The primary hydroxyl and secondary amino groups in 51 are affixed to adjacent carbon atoms. By virtue of this close spatial relationship, it seemed reasonable to expect that the simultaneous protection of these two functions in the form of an oxazolidi-none ring could be achieved. Indeed, treatment of 51 with l,l -car-bonyldiimidazole in refluxing acetonitrile, followed by partial reduction of the methoxycarbonyl function with one equivalent of Dibal-H provides oxazolidinone aldehyde 52. 

The highly strained and reactive 2iT-azirines have been extensively studied for various synthetic purposes, such as ring expansion reactions, cycloaddition reactions, preparation of functionalized amines and substituted aziridines. The older literature on azirines in synthesis has extensively been reviewed [69]. Concerning azirines with defined chirality only scarce information is available. Practically all reactions of azirines take place at the activated imine bond. Reduction with sodium borohydride leads to cz5-substituted aziridines as is shown in Scheme 48 [26,28]. 

The spiro compound 206 was prepared in five steps from (S)-l-naphthyl-ethylamine and was composed of a mixture of imine and enamine tautomers. Reduction of the imine function by sodium borohydride occurred on the less hindered si face, leading to the diamine with the R configuration of the newly formed stereo center, then the N-benzyl substituent was removed by hydrogenolysis to give 207 with good overall yield [98] (Scheme 30). 

By heating 2-benzyloxycyclohexanone 208 and (R)-l-phenylethylamine in refluxing toluene for 4 days in a Dean-Stark apparatus, the imine 209 was formed, then a rearrangement occurred to give first the a-aminocyclohexanone derivative 210 and finally the Q, o -disubstituted imine 211 with moderate diastereoselectivity. Reduction of this imine with sodium borohydride gave a mixture of two trans diamines (S,S)-212 and (R,R)-212, which were separated by chromatography. The enantiomers of 1-benzyl-1,2-diaminocyclohexanes 213 were then obtained by hydrogenolysis [99] (Scheme 31). 

Enantiopure 3-phenyl-2-cyanoazetidines (S)-238 and (K)-238, which are epimeric at C2, are prepared in high yields from (K)-phenylglycinol. A one-pot sequence, including addition of organohthium or allyhnagne-sium bromide to the cyano group and in situ reduction of the resulting imine with sodium borohydride, allowed for the preparation of 2-(l-aminoalkyl)azetidines, which were then protected as N-Boc derivatives (R,S)-239 and (S,it)-239 [112] (Scheme 36). Complete anti diastereoselectivity (dr more than 95 5 by NMR) was observed in both cases. The same sequence... 

Typically, the imine linkages can be reduced chemically (for example, using sodium borohydride in methanol), catalytically (for example, using H2 in the presence of a catalyst such as Pd/C) or electrochemically. The reduced ligands can normally be removed from their respective metal ions using one of a number of procedures. 

The reverse reaction, namely hydrogenation, has also frequently been used to decrease the degree of unsaturation present in macrocyclic systems - typically converting imine linkages to amine groups. Such hydrogenations have usually been performed catalytically (for example, using H2 in the presence of Raney nickel or a precious metal catalyst) or by means of chemical reductants such as sodium borohydride. 

Hydrogen will not reduce ketones or imines using CATHy or related catalysts. Inorganic hydrogen donors that have been used include dithionite and di-hydrogenphosphite salts, metal hydrides such as sodium borohydride, and sodium cyanoborohydride. Recently, amines have been shown to function as hydrogen donors with some catalysts. The enzymic cofactor NADH can be used stoichiometrically, and the potential exists to use this catalytically [56]. 

Phosphorylated allenes 195 (R1 = H or Me) are a source of secondary ( )-allylamines. The allenes are treated with an amine R2NH2 (R2 = t-Bu or 4-MeCgH4 and the products, which exist as equilibrium mixtures of enamines 196 and imines 197, are olefinated by successive reaction with methyllithium and an aldehyde R3CHO (R = i-Bu, 4-MeCgH4, PhCH2CH2 etc). Reduction with sodium borohydride finally yields the... 

A number of pendant arm ligand derivatives based on hexamine macrocyclic backbones have been reported." One such species was formed by the [2 -f 2] Schiff base condensation between 3,3-iminobis(propylamine) and diformyl-p-cresol followed by sodium borohydride reduction of the four imine functions so generated. Potentiometric studies indicate that a range of both mononuclear and dinuclear species are formed in solution with manganese(II) incorporating various both protonated and nonprotonated forms of the ligand. 

Arylmethyl-4H-pyrrolo[l,2-fl][l,4]benzodiazepines 236 can be transformed with sodium borohydride to corresponding derivatives reduced at the imine double bond (Scheme 50, Section 3.1.1.3 (1995EJM593)). 

Through a slight modification the Pomeranz-Fritsch synthesis can be made particularly useful for the preparation of 1,2-dihydroisoquinolines. The imine is first reduced with sodium borohydride in 98% ethanol to the corresponding benzylamine, prior to cyclization, by treatment with 6 M hydrochloric acid. When electron-donating groups (such as a methoxyl) are present in the aromatic unit of the benzylamine, the ring-... 

Alkyl-3-formylcarbazoles form-arylhydrazones " and azines or hydrazones with hydrazine. 9-Ethyl-3-formylcarbazole gives Schiflf bases with arylamines. Variously substituted 3-formylcarbazoles condense with aminoacetal, " and the resulting imines are easily reduced catalytically or with sodium borohydride. Anils from... 

Also other reaction types have been dealt with in CHEC(1984) and CHEC-II(19%) like reduction to alcohols (e.g., sodium borohydride), Wolff Kishner reduction, nucleophilic addition via reaction with Grignard reagents or organo-lithium compounds, and formation of imine type functional groups (e.g., hydrazones). New examples are the reaction of... 

In the special case of a-alkyl-a -nitro-substituted imines, reduction with sodium borohydride/ cerium(III) chloride and elimination of the chiral auxiliary generated the nitroalkene without racemization22. 

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