Cyclopropenylcarbinol Derivatives as New Versatile Intermediates in Organic Synthesis: Application to the Formation of Enantiomerically Pure Alkylidenecyclopropane Derivatives

Abstract

The copper-catalyzed carbomagnesiation (or hydrometalation) reaction of chiral cyclopropenylcarbinol derivatives, obtained by means of a kinetic resolution of secondary allylic alcohols, leads to an easy and straightforward preparation of enantiomerically pure alkylidenecyclopropane derivatives. The reaction mechanism is composed of a syn-carbometalation followed by a syn-elimination reaction. To gain further insight into the reaction mechanism of the carbometalation, the diastereoselective formation of cyclopropylcarbinol was also achieved and was found to be very sensitive to the nature of the organometallic species used for the addition reaction. Cyclopropylcarbinol could also be prepared through a diastereoselective reduction of cyclopropenylcarbinol derivatives. Finally, functionalization of enantiomerically enriched cyclopropenylcarbinols into the corresponding acetate or phosphinite derivatives leads, under mild conditions, to various enantiomerically pure heterosubstituted alkylidenecyclopropanes.

Stereoselective Synthesis of Trisubstituted Olefins by a Directed Allylic Substitution Strategy

“…Alternatively, starting from the identical reactive conformation 24 b, a directed carbocupration of the double bond may occur with sp 2 Grignard reagents. [26] A similar carbocupration mechanism has been postulated previously for the mechanistically related 1,4-cuprate addition to a,b-unsaturated carbonyl compounds. [27] Thus, the o-DPPB-directed carbocupration of the alkene function would furnish adduct 35 a.…”

Synthesis of Methylene‐ and Alkylidenecyclopropane Derivatives

“…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.…”

“…[82] The reaction proceeded smoothly when tertiary alcohols 106a-e were used whatever the nature of the R 2 substituent on the cyclopropenyl units (alkyl or aryl) and the nature of the Grignard reagents (R 5 = alkyl or aryl). Similarly, the reaction led to methylenecyclopropanes when primary alcohols 106f, g were employed as starting materials.…”

Selektive C‐C‐Bindungsspaltung zur stereoselektiven Synthese acyclischer Systeme

“…Somit bleibt die Integrität und damit die absolute Konfiguration des quartären Stereozentrums weitestgehend erhalten. [16,17] Werden also enantiomerenreine ACP wie (E)-10 [18] der Rhodiumkatalyse unterworfen, bilden sich die entsprechenden (E)-Homoallylsilane 14 und (E)-Homoallylborane 15 mit gleichbleibenden Enantiomerenverhältnissen, wie durch Bestimmung der Reaktionsprodukte, nach Reduktion der Doppelbindung und anschließender Oxidation, nachgewiesen wurde (Schema 7). [14,18,19] Die Palladium-katalysierte C-C-Bindungsspaltung des meso-Methylencyclopropans 17 führt zur regioselektiven Einführung einer Silyl-und Borylgruppe [20,21] an die gespaltene C-C-Bindung.…”