Scope and Mechanism for Lewis Acid-Catalyzed Cycloadditions of Aldehydes and Donor−Acceptor Cyclopropanes: Evidence for a Stereospecific Intimate Ion Pair Pathway

Abstract

In this work, the one-step diastereoselective synthesis of cis-2,5-disubstituted tetrahydrofurans via Lewis acid catalyzed [3 + 2] cycloadditions of donor-acceptor (D-A) cyclopropanes and aldehydes is described. The scope and limitations with respect to both reaction partners are provided. A detailed examination of the mechanism has been performed, including stereochemical analysis and electronic profiling of both reactants. Experimental evidence supports an unusual stereospecific intimate ion pair mechanism wherein the aldehyde functions as a nucleophile and malonate acts as the nucleofuge. The reaction proceeds with inversion at the cyclopropane donor site and allows absolute stereochemical information to be transferred to the products with high fidelity. The mechanism facilitates the stereospecific synthesis of a range of optically active tetrahydrofuran derivatives from enantioenriched D-A cyclopropanes.

Total Synthesis of (+)‐Isatisine A

“…The tetrahydrofuran ring in 6, which represents a central structural feature of the natural product, would be prepared through the elegant cyclopropane-aldehyde cycloaddition developed by Johnson and co-workers, [6] between an indole-2-carboxaldehyde 7 and a suitable cyclopropane-1,1-diester 8. The S configuration of the cyclopropane as shown would set the C10 and C12 stereocenters as R and S, respectively, by virtue of stereospecific inversion upon ring-opening in the cycloaddition process and a cis diastereoselectivity in the tetrahydrofuran synthesis.…”

Metalltriflimidate sind bessere Katalysatoren für die organische Synthese als Metalltriflate – der Effekt eines stark delokalisierten Gegenions

“…[107] AgNTf 2 , das einzige für diese Reaktion untersuchte Triflimidat, war ein besserer Katalysator als AgOTf, doch mehrere Metalltriflate, insbesondere Sn(OTf) 2 , lieferten ebenfalls gute Ergebnisse (Schema 11). …”

Domino Cyclodimerization of Indole‐Derived Donor–Acceptor Cyclopropanes: One‐Step Construction of the Pentaleno[1,6‐a,b]indole Skeleton

“…In contrast, moderately activating Lewis acids in low-polar solvents usually give rise to intimate-ion-pair formation. [15,16] The coupling of electrophilic and nucleophilic centers of two intermediates X yields dimeric zwitterionic intermediate Y. This step is analogous to the first step in the dimerization of 2-(indolyl)cyclopropyl ketones.…”