Intramolecular Schmidt Reactions of Alkyl Azides with Ketones: Scope and Stereochemical Studies

Abstract

The intramolecular Schmidt reaction of alkyl azides and ketones has been demonstrated. The reaction is proposed to occur via initial attack of an azide on a ketone activated by a variety of protic or Lewis acids, including trifluoroacetic acid, titanium tetrachloride, and others. The resulting azidohydrin undergoes a direct rearrangement to afford the product amide and molecular nitrogen. When cyclic ketones are used, fused bicyclic lactams of types encountered in a wide variety of natural products are obtained. Although the distance allowed between the carbonyl group and the alkyl azide is quite restricted, the reaction is general with respect to the ketone component, including acyclic ketones and cyclic substrates ranging from standard to large ring sizes. The reaction also succeeds with aldehydes, although elimination or hydride migration products compete. In several cases examined, the reaction was found to proceed with retention of configuration at the migrating carbon. Competing reactions with P-diketones and a$-unsaturated ketones were found to predominate over ring expansion. @

Revisiting a Classic Approach to the Aspidosperma Alkaloids: An Intramolecular Schmidt Reaction Mediated Synthesis of (+)-Aspidospermidine

“…Although such selectivity had not been demonstrated prior to this work, model studies showed that compounds with four carbons separating the two reactive moieties underwent ring expansion chemistry much more easily than those with only three, which would support the selective formation of the desired product. 6 We envisioned an asymmetric synthesis of a precursor enone 8 or 9 from 2-ethylcyclopentanone 12 using the asymmetric variant of the Robinson annulation invented by d'Angelo's group, 7 thus establishing the critical quaternary stereocenter in the desired configuration.…”

Structural Stability and Vibrational Analyses of Haloselenonyl Azides, XSeO2-NNN, where X is F, Cl, Br

“…The very high reactivity and the application of organoazides in synthetic chemistry and many important industries [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] has drawn the attention to investigate the structure and conformational behavior of vinyl azide, CH2=CH-NNN [37] and formyl azide, CHO-NNN [38], by DFT and ab initio MP2 calculations. Both molecules were predicted to have a cis/trans conformational equilibrium with the gauche form being the transition state.…”

DBU as a catalyst for the synthesis of amides via aminolysis of methyl esters

“…As expected, ester 2 was more reactive than 1 and the corresponding amides 9a and 9b were formed in better yields, in both conditions (79-90%), but the reactions were considerably faster in the presence of DBU (entries [7][8][9][10]. Once again in the reaction with aniline 7, the corresponding amides were not formed, regardless the use of DBU (entries 11 and 12).…”

“…The analytical data of amides 8a-c and 9a-c were identical to those reported previously. 10 New amides 10a-c and 11a-c were characterized by 1 H NMR, 13 C NMR and MS.…”