Stereochemistry of the Deamination of Spiropentylamine

Abstract

The stereochemistry of the deamination of (−)-spiropentylamine in acetic acid has been studied, and it was found that one of the major products, (−)-spiropentyl acetate, was formed with essentially complete inversion of configuration. This suggests that it is formed via an SN2 displacement on the spiropentyldiazonium ion. The stereochemistry was established by the conversion of (−)-spiropentanecarboxylic acid to (−)-spiropentylamine via a Curtius rearrangement that proceeds with retention of configuration. The (−) acid also was converted to spiropentyl methyl ketone with methyllithium and then to (+)-spiropentyl acetate via the Baeyer−Villiger reaction that also results in retention of configuration. The deamination of N-nitroso-N-spiropentyl urea was studied in methanol, and spiropentyl methyl ether was a major product. Similarly, the reaction in water led to spiropentanol. The latter reactions also lead to 2-methoxymethyl- or 2-hydroxymethyl-1,3-butadiene, respectively, corresponding to the alternative mode of reaction via a cyclopropyl cation−allyl cation rearrangement.

Configurational and Conformational Analysis of Chiral Molecules Using IR and VCD Spectroscopies: Spiropentylcarboxylic Acid Methyl Ester and Spiropentyl Acetate

“…The ACs of 1 and 2 are thus unambiguously R (−) / S (+) and R (+)/ S (−), respectively. The AC reported earlier for 2 was R (+)/ S (−) . The AC reported earlier for 4 was R (−)/ S (+) .…”

“…The stereochemistry and mechanism of the nitrous acid deamination of spiropentylamine in acetic acid was recently studied . Optically active spiropentylamine, 3 , and spiropentyl acetate, 2 , of known relative configurations were prepared from optically active spiropentylcarboxylic acid, 4 , using reactions of known stereochemistry (Scheme ), and the specific rotations of 2 and 3 established.…”

“…Measurement of the specific rotation of 2 obtained by deamination of optically active 3 then led to the conclusion that deamination occurs with essentially complete inversion of configuration, consistent with S N 2 displacement at a spiropentyldiazonium ion intermediate. Simultaneously, the absolute configuration (AC) of 4 was determined via X-ray crystallography of its salt with ( S )-(−)-α-phenylethylamine to be R (−)/ S (+) . This in turn allowed the ACs of 2 and 3 to be inferred: 2 , R (+)/ S (−); 3 , R (−)/ S (+).…”

Rearrangements of Spiropentyl Cation

“…Thus, the deamination should lead to the acetate having an inverted configuration. This has been tested experimentally and the reaction is found to give complete inversion of configuration …”

A Solid-Phase Synthesis of N,N‘-Disubstituted Ureas and Perhydroimidazo[1,5-a]pyrazines via the Curtius Rearrangement

“…An important utilitarian feature of this reaction is that a diverse assortment of carboxylic acids can be converted into their corresponding acyl azides which can undergo thermal rearrangement to isocyanates in one pot. Useful carboxylic acids include aliphatic, aromatic, heterocyclic, unsaturated, and chiral acids . Since the number of commercially available carboxylic acids greatly exceed the corresponding pool of isocyanates, the Curtius rearrangement has been used with great success to access noncommercially available isocyantes as they are required in a particular synthesis.…”