Enantiomerenangereicherte Cyclopropene: vielseitige Bausteine in der asymmetrischen Synthese

Abstract

Enantiomerenangereicherte Cyclopropenderivate, die kleinstmöglichen ungesättigten Carbocyclen, sind von großem Interesse für die Synthese, da sie als vielseitige reaktive Bausteine eingesetzt werden können. Die Reaktivität rührt von der Ringspannung her, die durch Umsetzungen gemildert wird. Die Cyclopropenderivate können zu komplexeren chiralen Strukturen umgesetzt werden, wobei in diesem Aufsatz besonders die Herstellung von enantiomerenangereicherten Methylen‐ und Alkylidencyclopropanderivaten herausgehoben wird. Die einfache Verfügbarkeit chiraler Bausteine dieser Art bildet eine ausgezeichnete Grundlage für die Entdeckung neuartiger Reaktionen, die das Repertoire der organischen Synthese bereichern können.

Synthesis of Methylene‐ and Alkylidenecyclopropane Derivatives

“…A novel [2,3]-rearrangement of cyclopropenylmethyl phosphinites to methylenecyclopropylphosphane oxides was demonstrated by Rubin et al [85] As shown in Scheme 38, these authors developed the one-pot transformation of alcohols 112a-d into diasteromeric mixtures of methylenecyclopropylphosphane oxides 114a-e and 115a-e without the isolation of the sensitive phosphinites 113a-d in high yields and moderate diastereoselectivities of up to 68% de. It was found that, in striking contrast to the analogous rearrangement known for unstrained allylic systems, this reaction did not proceed at all upon thermal activation; however, it could be efficiently mediated by a base such as DBU.…”

“…The [2,3]-sigmatropic rearrangement of allylic diphenylphosphinites 117a-g generated from the corresponding alcohols 116a-g was also investigated by Marek et al [82] As shown in Scheme 39, primary, secondary and tertiary cyclopropenyldiphenylphosphinite derivatives 117a-d were rearranged within a few minutes into the corresponding phosphane oxide of methylene-and alkylidenecyclopropanes 118a-d in excellent yields. As the design and preparation of chiral phosphanes for asymmetric catalysis is an active area of research, the scope of the methodology was extended to chiral cyclopropenyldiphenylphosphinites 117e-g which provided the corresponding (E)-and (Z)-alkylidenecyclopropane diphenylphosphane oxide derivatives 118e, f in an 80:20 E/Z ratio with a complete transfer of chirality, as shown in Scheme 39.…”

“…In order to further enrich the chemistry of cyclopropenylcarbinols in synthesis, the same authors have used the release of strain of the three-membered ring to promote easy sigmatropic rearrangements as a new route to alkylidenecyclopropanes possessing polar functionalities, such as acetoxyalkylidenecyclopropane derivatives. [82,84] As shown in Scheme 37, the [3,3]-sigmatropic rearrangement of tertiary allylic acetates 110a-f could be performed under very mild conditions either by simple filtration through column chromatography on silica gel (method A), by heating at reflux in CH 2 Cl 2 (method B), or by addition of dry acidic ion-exchange resin Amberlyst-15 (method C). In all cases, the rearrangement occurred to give the expected methylenecyclopropanes 111a-f in excellent yields.…”

“…As the design and preparation of chiral phosphanes for asymmetric catalysis is an active area of research, the scope of the methodology was extended to chiral cyclopropenyldiphenylphosphinites 117e-g which provided the corresponding (E)-and (Z)-alkylidenecyclopropane diphenylphosphane oxide derivatives 118e, f in an 80:20 E/Z ratio with a complete transfer of chirality, as shown in Scheme 39. Shi et al reported the formation of methylenecyclopropanes 120a-g through the addition of hydrogen peroxide in the presence of pyridine to selenides 119a-g. [86] The formation of these novel functionalized products, obtained in moderate to good yields as mixtures of E/Z isomers, was rationalized through a [2,3]sigmatropic rearrangement depicted in Scheme 40. The selenide 119, which has two conformations (119A and 119B), was oxidized to form the corresponding intermediates 121A and 121B, respectively.…”

“…Due to the limited degrees of freedom in the system, these conformationally constrained molecules have very pronounced steric, stereoelectronic, and directing effects, which make them versatile probes for the study of regio-, diastereo-, and enantioselectivity. [3] Furthermore, a diverse reactivity pattern resulting from the significant strain energy accounts for the use of small carbocycles as convenient models for the investigation of organic and organometallic reaction mechanisms. There is also a growing interest in small carbocycles from the related fields of medicinal and biological chemistry.…”