Stereoselective Synthesis of Chiral 2,3-cis-2-Ethynylaziridines by Base-Mediated Intramolecular Amination of Bromoallenes

Abstract

[reaction: see text] Novel stereoselective synthesis of 2,3-cis-2-ethynylaziridines from amino allenes is presented. While sodium hydride mediated intramolecular amination of (4S,aS)-4-alkyl-4-[N-(arylsulfonyl)amino]-1-bromobuta-1,2-dienes yields a mixture of 2,3-cis- and 2,3-trans-2-ethynylaziridines in which the cis-isomer predominates (79:21-89:11), the amination of (4S,aR)-isomers affords 2,3-cis-aziridines in excellent selectivities (91:9-100:0). Conversion of 2,3-trans-2-ethynylaziridines into the corresponding cis-isomers via a sequence of reactions (methanesulfonic acid mediated ring-opening reaction, bromination, and aziridination) is also described.

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.…”

“…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.…”

Bromoallenes as Synthetic Equivalents of Allyl Dications: Synthesis of Medium‐Sized Nitrogen Heterocycles through the Cyclization of Bromoallenes in the Presence of a Palladium(0) Catalyst and an Alcohol

“…[6][7][8] In contrast, as far as we are aware, ring-forming reactions of bromoallenes have scarcely been studied. [9] This Communication is based on a new finding that the bromoallene 1 can act as allyl dication equivalent 4 when treated with palladium(0) in an alcohol solvent, presumably by the mechanism shown in Scheme 1. [10] Although similar types of reaction are often observed with propargylic carbonates in the presence of a palladium catalyst and a soft nucleophile such as active methylene, aryl alcohols, or amides, [10,11] the reaction of allenic substrates and the synthesis of eight-membered rings are unprecedented.…”

“…When the reaction was carried out in THF in the presence or absence of palladium (Table 1, entries 3 and 4), cis-2-ethynylaziridine 12 was obtained as a single isomer, consistent with the results of our previous study. [9] Next, according to the working hypothesis depicted in Scheme 2, we investigated the synthesis of medium-sized heterocycles through the cyclization of bromoallenes in the presence of a palladium catalyst. To investigate the effect of axial chirality on the cyclization reaction, diastereomerically pure (S,aS)-bromoallenes 14 a-i were prepared from known intermediates.…”

“…To investigate the effect of axial chirality on the cyclization reaction, diastereomerically pure (S,aS)-bromoallenes 14 a-i were prepared from known intermediates. [9] The results of the cyclization reactions are summarized in Table 2. Bromoallene 14 a, which bears an oxygen functionality, was treated with NaOMe (1.5 equiv) in MeOH in the presence of [Pd(PPh 3 ) 4 ] (5 mol %) to afford the seven-membered ring 15 a (73 %) and a small amount of its regioisomer 16 a (9 %; Table 2, entry 1).…”