Stereocontrolled Syntheses of Seven‐Membered Carbocycles by Tandem Allene Aziridination/[4+3] Reaction

Abstract

A tandem allene aziridination/[4+3]/reduction sequence converts simple homoallenic sulfamates into densely functionalized aminated cycloheptenes, where the relative stereochemistry at five contiguous asymmetric centers can be controlled through the choice of the solvent and the reductant. The products resulting from this chemistry can be readily transformed into complex molecular scaffolds which contain up to seven contiguous stereocenters.

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 nitrogen-containing heterocycles

“…92 In this manner, the stereochemistry of the subsequent [4+3] cycloaddition with furan to furnish 133 could be altered in a tunable manner. 93 Likewise, reagent-controlled reduction in the transformation of 133 to 134 provides an opportunity to vary the relative stereochemistry between the amine at C2 and the stereochemistry at C1 and C3 of the original allene precursor. In this manner, stereodivergent syntheses of four different stereoisomers of 134 from a single allene might be accomplished.…”

“…Addition of a 1:1 mixture of furan/THF furnished the 1,3-syn heterocycle 139 through the intermediacy of 137, whereas a 1:1 furan/MeNO 2 mixture delivered the 1,3-anti heterocycle 142 via 138. 93 Further stereodivergence was accomplished in reagent-controlled reduction of the imines of 139 and 142. Small hydrides, such as NaBH 3 CN, favored approach of the nucleophile from the top face of 139 to furnish 141, while reaction of 142 provided 144.…”

“…The reaction sequence could be accomplished in one pot, with moderate yields over the three steps (Scheme 18, bottom for one example) and moderate-toexcellent dr. As expected, formation of the achiral 2-amidoallyl cation precluded effective transfer of axial-topoint chirality; however, an external asymmetric center was able to control the diastereoselectivity of the [4+3] reaction to yield product in 97% ee (not shown). 93 Scheme 18. Stereodivergent, [4+3] cycloadditions of furan with 2-amidoallyl cations from allenes.…”

Rh(II)-Catalyzed Nitrene-Transfer [5 + 1] Cycloadditions of Aryl-Substituted Vinylcyclopropanes

“…Our strategy relies on the hypothesis that in certain cases, nitrene transfer to the olefin of a vinylcyclopropane (VCP) might produce a substituted cyclopropylcarbinyl cation or radical, arising either directly from the olefin or from an intermediate aziridine . Either cyclopropylcarbinyl species, if sufficiently long-lived, would be expected to promote cyclopropane C–C bond cleavage, ultimately providing a ring-expanded [5 + 1] cycloaddition product (specifically a tetrahydropyridine) after a subsequent cyclization (Scheme b) .…”