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

• Published in: Journal of the American Chemical Society Vol. 130; no. 27; pp. 8642 - 8650
• Main Authors: Pohlhaus, Patrick D, Sanders, Shanina D, Parsons, Andrew T, Li, Wei, Johnson, Jeffrey S
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 09.07.2008; Amer Chemical Soc
• Subjects: Aldehydes - chemistry; Benzaldehydes - chemistry; Catalysis; Chemistry; Chemistry, Multidisciplinary; Cyclopropanes - chemistry; Furans - chemical synthesis; Mesylates - chemistry; Molecular Structure; Physical Sciences; Science & Technology; Stereoisomerism; EXPANSION REACTION; DIASTEREOSELECTIVE SYNTHESIS; DIPOLAR CYCLOADDITION; ALKYLATION; RING-OPENING REACTIONS; REACTIVITY; STEREOSELECTIVE-SYNTHESIS; DERIVATIVES; SUBSTITUTED CYCLOPROPANES; CYCLO-ADDITION
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja8015928

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.