Microwave-assisted reactions of allenic esters: [3+2] annulations and allenoate-Claisen rearrangement

Abstract

The reactivity of allenic esters towards an activated N-sulfonylimine and electron-deficient alkenes with a phosphine under microwave irradiation is explored. The methodology is shown to be efficient for the one-step synthesis of 3-pyrrolines and cyclopentenes in a regio-and diastereoselective manner. This formal [3+2] cycloaddition is complete within five minutes. It was also demonstrated that microwave irradiation is the best energy source to carry out the Lewis acid catalyzed allenoate-Claisen rearrangement leading to 3-(pyrrolidin-1-yl)hepta-2,6-dienoates.

Phosphine Organocatalysis

“…Furthermore, many asymmetric variations of the reaction have been reported. Interestingly, Lu’s reaction had also been investigated under catalysis of a polymer -supported phosphine and under microwave irradiation …”

“…Interestingly, Lu's reaction had also been investigated under catalysis of a polymer-supported phosphine 242 and under microwave irradiation. 243 In the mechanism proposed by Lu, both 2-butynoates and 2,3-butadienoates are capable of generating the phosphonium dienolate 77, which undergoes nucleophilic addition preferably at the carbon α to the electron-deficient olefin, yielding the intermediate 113 (Scheme 184). Upon addition, the electrophilic olefin becomes a transient carbanion that acts as a nucleophile and undergoes addition to the vinylphosphonium portion of the intermediate 113.…”

Enantioselective Allenoate-Claisen Rearrangement Using Chiral Phosphate Catalysts

“…In contrast, truly catalytic enantioselective Claisen rearrangements have only been reported with a limited number of systems, mostly based on chiral Lewis acids . In this context, we were intrigued by the so-called allenoate-Claisen rearrangement, an elegant, Lewis acid-catalyzed variant developed by Lambert and MacMillan in 2002, for which a highly enantioselective version remains elusive. In this transformation, an allenoate ester reacts with a tertiary allylamine to form a zwitterionic allyl-vinylammonium intermediate (Figure A and B), containing charge separation to facilitate a [3,3]-sigmatropic rearrangement.…”

Asymmetric Aza-Claisen Rearrangement between Enantioenriched α-Chiral Allylamines and Allenones

“…Charge acceleration has been frequently employed as a powerful strategy to decrease the reaction temperature via converting allylamines into the corresponding ammonium salts through protonation, Lewis acid coordination, or quaternization prior to the aza-Claisen rearrangement. Particularly, zwitterionic aza-Claisen rearrangements can proceed under relatively mild conditions after nucleophilic addition of tertiary allylamines to π-electrophiles such as 2-alkynoates, acetylenic sulfones, allenoates, ketenes, , ketenimines, carbodiimides, isocyanates, and isothiocyanates . While stereochemical advantages can be expected from the aza-Claisen rearrangements because of their chair-like six-membered transition states with minimized repulsive interactions, only l -(−)-proline-derived α-chiral allylamines have been reported previously to exhibit effective 1,3-chirality transfer in the ketene-mediated rearrangement/ring-expansion reaction (Scheme a). ,, To our knowledge, 1,3-chirality transfer has not yet been disclosed for the aza-Claisen rearrangement of other types of enantioenriched α-chiral allylamines, which, though, can be readily accessible by resolution of the racemic ones with inexpensive chiral acids .…”

“…Inspired by previous reports on the zwitterionic aza-Claisen rearrangements of π-electrophile-activated tertiary allylamines, − we initiated our investigation on a possible asymmetric aza-Claisen rearrangement between enantioenriched α-chiral allylamines and allenones, wherein retention of enantiopurity was expected via a chair-like six-membered transition state with minimized repulsive interactions (Scheme b). To our delight, simply treating allylamine rac - 1a with allenone 2a in dichloromethane at room temperature afforded β-amino enone rac -3a in 85% NMR yield (Table , entry 1).…”