Sodium compounds nucleophilic trapping

Even if the imine may not be isolated, the transient species may sometimes be trapped by reaction with a suitable nucleophile. This is the basis of the reductive amination reaction in which an amine is formed from the reaction of ammonia with a carbonyl compound in the presence of a reducing agent such as sodium borohydride or formate. Use of a primary or secondary amine results in the specific formation of secondary or tertiary amines respectively (Fig. 5-45). This synthetic method allows the preparation of high yields of amines, in contrast to the unselective and uncontrollable reaction of alkylating agents with amines. A specific example involving the preparation of a-phenylethylamine from acetophenone is presented in Fig. 5-46. 

Support for the new mechanism was provided by trapping the intermediate with methyl iodide to give epoxide 133. The structure of this compound was indicated by IR absorption at 1646 cm- (2-quinolone carbonyl) and by the NMR spectrum. The epoxide was converted readily into the diol balfourolone (135) on alumina chromatography or by treatment with 2 N sodium hydroxide at 20° the mild conditions and the failure of 2,4-dimethoxyquinoline epoxides (e.g., 109) to react under similar conditions suggest that this reaction occurs through formation of O-methylbalfourodinium salt (134) and subsequent nucleophilic attack at the 2-position rather than by direct reaction of hydroxide ion on the epoxide ring. Epoxide 133 is the presumed intermediate in reaction of 4-methoxy-... 

Evidence for the intermediacy of the enamine (138) and the immonium ion (140) derives from the condensation reaction in which potassium cyanide replaced sodium cyanoborohydride the immonium ion (140) was thus trapped by reaction with nucleophilic cyanide ion, with formation of 21-cyanotetrahydroalstonine (141a) and 21-cyanoakuammigine (141b). Both cyano-compounds suffered slow reduction to the parent alkaloid by sodium borohydride, and were re-converted (by silver acetate) into the precursor immonium ions (140), which could be rapidly reduced (NaBH4) to the alkaloids. Scheme 17 illustrates some, but not by any means all, of the numerous interconversions involved in these biomimetic experiments. 

C-Labelling showed that the thermal conversion of the phenyl trimethylsilyl diazo-compound (168) into (169) involved isomerization of a phenyl carbene into a cycloheptatrienylidene, silacyclopropanes were not involved. It was shown that the P-naphthyl carbene obtained by rearrangement of 4,5-benzocycloheptatrienylidene enters the singlet-triplet manifold as a singlet. Evidence has been reported that aryl carbenes can show both electrophilic and nucleophilic properties in their intramolecular ring expansion. Low-temperature photolysis of the sodium salt of the toluene-p-sulphonyl hydrazone (170) gave, by intramolecular carbene addition, the dibenzobicyclo[4,l,0]heptatriene (171) which was trapped by buta-l,3-diene. ... 

In subsequent studies, the scope of the Heck reaction/ anion-trapping cascade was further extended using soft car-banionic nucleophiles as illustrated in the asymmetric synthesis of (—)-D -capnellene 17. Treatment of prochiral vinyl triflate 15 with Pd(OAc>2, (5)-BINAP, and NaBr, as weU as the sodium enolate of diethyl (2-((rert-butyldiphe-nylsilyl)oxy)ethyl)malonate, gave the cyclic product 16 in 87% ee and 77% yield as the sole product. The use of NaBr as an additive improved the optical yields and was critical in preventing counteranion exchange between the triflate anion and the enolate anion by complexing with sodium enolate (Scheme 13.6). Compound 16 was then advanced through several steps to complete the total synthesis (—)-D -capnellene 17. 

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