A Highly cis-Selective Synthesis of 2-Ethynylaziridines by Intramolecular Amination of Chiral Bromoallenes:  Improvement of Stereoselectivity Based on the Computational Investigation

Abstract

The base-mediated intramolecular amination of bromoallenes having an axial chirality is described. The treatment of (4S,aR)-4-alkyl-4-[N-(arylsulfonyl)amino]-1-bromobuta-1,2-dienes with NaH in DMF affords 2,3-cis-2-ethynylaziridines in good to excellent selectivity (2,3-cis:trans = 92:8-99:1). The reaction of (4S,aS)-bromoallenes with NaH/DMF also gives 2,3-cis-2-ethynylaziridines selectively (79:21-91:9). These experimental results have been rationalized by B3LYP density functional calculations together with the 6-31+G(d) basis set and the Onsager solvation model. The transition structures for cis-aziridine formation of both (4S,aR)- and (4S,aS)-bromoallenes in DMF are favored over the corresponding trans transition structures by 4.35 and 1.41 kcal/mol, respectively. Furthermore, the calculations predicted that a less polar solvent gives higher cis selectivity for (4S,aS)-bromoallenes. In fact, improvement of the cis selectivity to 99:1 has been realized by using a less polar solvent such as THF. The cyclization of bromoallenes bearing a beta- or gamma-amino group also affords four- and five-membered azacycles in a highly cis-selective manner.

Density Functional Theory Study of Solvent Effects on the Structure and Vibrational Frequencies of Tetranitrotetraazabicyclooctane “bicyclo-HMX”

“…Since then, this model has been applied to a number of problems with the use of semi-empirical MO theory, [16][17][18][19][20] and some applications using density functional theory have been reported. [21][22][23][24] In addition, since the Onsager model does not account for local interactions, only a gross estimate of the solvent effect of water, a kind of H-bonding solvent, was provided. Thus, in this paper, the effects of five solvents, i.e.…”

“…This theory has been successfully applied to many problems with the use of both semi-empirical methods [16][17][18][19][20] and DFT methods. [21][22][23][24] In this paper, we have used the DFT SCRF theory to study the effects of different solvents on the structure and spectroscopic properties of bicyclo-HMX.…”

Development of Useful Reactions Involving Tandem Cyclizations Based on the Novel Reactivities of Allenic Compounds

“…Although the reaction mechanism of this cyclopropanation is not understood, this reaction clearly demonstrates a novel reactivity of allenes with a palladium (0) 129,130) Reactions of bromoallenes have attracted much interest in recent years, because of their cumulated double bonds and high reactivity. 131) These reactions involve organocopper-mediated substitutions, 132,133) palladium-catalyzed cross-coupling reactions, 134) and the formation of nucleophilic allenylmetal reagents.…”

“…These results are in good agreement with the computational investigation by Prof. Ando. 130) [152][153][154] Medium-sized heterocycles are an extremely important class of compounds, the structural units of which are commonly found within the framework of a variety of natural products. 155) In particular, seven-and eightmembered heterocycles are constituents of a number of compounds with interesting pharmacological properties.…”

“…In the course of our examination of the aziridination reaction of bromoallenes (Section 4.1), 129,130) it was found that the reaction of bromoallene 131a with Pd(PPh 3 ) 4 and NaOMe in MeOH provided 2,3-cis-2-(1-methoxy)vinylaziridine 138 stereoselectively (Chart 18). This result strongly suggests the formation of h 3 -allylpalladium complex 137 bearing a methoxy group on the central carbon.…”