Phosphine-Catalyzed Chemo- and Diastereoselective [2 + 2 + 2] and [3 + 2] Annulations of γ-Methyl Allenoates with Doubly Activated Olefins: Syntheses of Highly Substituted Cyclohexanes and Cyclopentenes

Abstract

Phosphine-catalyzed chemoselective [2 + 2 + 2] and [3 + 2] annulations of γ-methyl allenoates with doubly activated olefins have been developed, which afford highly substituted cyclohexanes bearing five continuous stereogenic centers and cyclopentenes bearing three continuous stereogenic centers, respectively, in generally high yields with excellent diastereoselectivity. The [2 + 2 + 2] annulation represents an unprecedented reactivity pattern of γ-methyl allenoates with activated CC bonds to access six-membered carbocycles. In addition, the study herein also evidences that the acidic protic additives such as benzoic acid can exert influence on chemoselectivity of phosphine-catalyzed annulation reactions involving allenoates.

Phosphine‐Catalyzed [3+2] and [2+4] Annulations of γ‐Methyl Allenoates with Aryl α‐Keto Esters: Stereoselective Syntheses of Functionalized Tetrahydrofurans and 4‐Chromanols

“…According to our previous closely related studies and current observation, a plausible mechanism to account for the formation of tetrahydrofurans 3 and 4‐chromanols 5 is proposed in Scheme . The nucleophilic attack of phosphine catalyst at the β‐carbon of allenoate 1 initially generates the resonance‐stabilized zwitterionic intermediates A and B .…”

“…resulted in slight decreases in both the yield and the diastereoselectivity (entry 6). Furthermore, addition of protic additives such as benzoic acid and ethanol did not exert any positive influence on the annulation (entries 7–8) . Elevating the reaction temperature to reflux led to an inferior result (entry 9).…”

“…A brief survey on the model reaction conditions was conducted to further improve its efficiency. Addition of an acidic additive such as benzoic acid interrupted the annulation (entry 2) . A slight improvement in the yield of 3 a was observed without influence the stereoselectivity when elevating the reaction temperature to reflux (entry 3).…”

Azide Radical Initiated Ring Opening of Cyclopropenes Leading to Alkenyl Nitriles and Polycyclic Aromatic Compounds

“…A Corey–Chaykovsky cyclopropanation led to 15 in 54 % yield [26] . Alkene 2 underwent a (3+2) annulation with allenoate 16 , delivering cyclopentene 17 in 89 % yield [27] . 2 could also be engaged in a Diels–Alder cycloaddition with Danishefsky's diene 18 , [28] leading to cyclohexenone 19 after acidic deprotection in 64 % yield.…”

Azide Radical Initiated Ring Opening of Cyclopropenes Leading to Alkenyl Nitriles and Polycyclic Aromatic Compounds

“…[26] Alkene 2 underwent a (3+2) annulation with allenoate 16, delivering cyclopentene 17 in 89 % yield. [27] 2 could also be engaged in a Diels-Alder cycloaddition with Danishefskys diene 18, [28] leading to cyclohexenone 19 after acidic deprotection in 64 % yield. We then investigated the possibility to engage cyano-stilbene derivatives such as 14 into an oxidative photocyclization.…”