The conversion of allenes to strained three-membered heterocycles

Abstract

This article reviews methods for converting allenes to strained, three-membered methylene heterocycles, and also covers the reactivity of these products. Specifically, the synthesis and reactivity of methylene aziridines, allene oxides/spirodiepoxides, methylene silacyclopropanes, methylene phosphiranes, and methylene thiiranes are described, including applications to the synthesis of complex molecules. Due to the primary focus on heterocyclic motifs, the all-carbon analogue of these species (methylene cyclopropane) is only briefly discussed.

Intermolecular [3+3] ring expansion of aziridines to dehydropiperi-dines through the intermediacy of aziridinium ylides

“…We previously leveraged the unusual strain (~42 kcal/mol) in methyleneaziridine 1a to achieve a formal [3+1] reaction to furnish methyleneazetidine 1d upon exposure to rhodium-supported carbene 1b ( Fig. 2a) [55][56][57][58][59][60][61][62] . Mechanistic studies support initial formation of the aziridinium ylide 1c, which subsequently undergoes a highly asynchronous, concerted [2,3]-Stevens rearrangement to form 1d 63 .…”

Oxidative Allene Amination for the Synthesis of Azetidin‐3‐ones

“…Our group has been engaged in developing an array of oxidative allene amination strategies that provide both heteroatom and stereochemical diversity for the synthesis of complex amine stereotriads that contain three contiguous and heteroatom-bearing chiral carbons (Scheme 2). [9] Ak ey component of our strategy is ah ighly chemo-, regio-, and 10] Our first challenge was to ascertain how the identity and the specific substitution pattern of the groups on the allene could be employed to reliably divert aziridination to the distal double bond. Placing ab ulky tert-butyl group at C1 of the homoallenic sulfamate 1 (Scheme 3) did not completely prevent aziridination yielding a2 :1 mixture of exo-and endocyclic bicyclic methyleneaziridines 2a and 2b.…”

“…In our previous studies involving Rh-catalyzed aziridination of the proximal double bond of homoallenic sulfamates, the transfer of axial to central chirality occurred with excellent fidelity to give enantioenriched amines. [9] To ensure that this same transfer of axial chirality was operative in the synthesis of these heterocycles,t he synthesis of the enantioenriched TBS-azetidinone (Scheme 6) was accomplished starting from (R)-(+ +)-3-butyn-2-ol, employing the same methodology used to synthesize racemic analogues.The enantioenriched azetidinone was derivatized by opening of the sulfamate ring with thiophenol to provide achromophore for chiral HPLC analysis.T he product 42 was isolated with 96 % ee.T he low yield was due to aside reaction initiated by deprotonation of 41,f ollowed by electrocyclic ring-opening and hydrolysis to 43 (see SI for details). Nonetheless,t his experiment clearly showed effective transfer of the axial chirality of the allene to the azetidin-3-one.…”

Oxidative allene amination for the synthesis of nitrogen-containing heterocycles

“…Based on literature precedent and our initialinvestigations, controlling the regioselectivity of intermolecular allene aziridination was difficult and often led to unstable products. [51][52][53] In contrast, intramolecular aziridination of homoallenic sulfamates of the form 1 (Scheme 2) using a dinuclear Rh(II) catalyst, such as Rh 2 (TPA) 4 (TPA = triphenylacetate), yielded exocyclic methyleneaziridines of the form 2 with excellent chemo-, regio-, and stereoselectivity. [54][55][56] While the labile 2 could be observed by NMR, it was readily opened in the presence of water or silica gel.…”