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  • Title: Ylide-initiated michael addition-cyclization reactions beyond cyclopropanes.
    Author: Sun XL, Tang Y.
    Journal: Acc Chem Res; 2008 Aug; 41(8):937-48. PubMed ID: 18656968.
    Abstract:
    [Reaction: see text]. Ylides are nucleophiles that bear a unique leaving group, L n M, and can attack aldehydes, ketones, imines, and electron-deficient alkenes. Over the course of the reaction, they react with CX (X = C, N, O, etc.) double bonds to form betaine or oxetane intermediates, which further eliminate the heteroatom-containing group in one of two ways to give the corresponding olefination or cyclization product. Since the discovery of the Wittig reaction, ylide olefination has developed as one of the most useful approaches in constructing carbon-carbon double bonds. These reactions provide unambiguous positioning of the C-C double bond and good stereoselectivity. Researchers have also widely used ylides for the synthesis of small ring compounds such as epoxides, cyclopropanes, and aziridines. However, the use of ylides to prepare larger cyclic structures was very limited. This Account outlines our recent work on ylide-initiated Michael addition/cyclization reactions. By altering the heteroatoms and the ligands of the ylides, we have modulated the reactivity of ylides. These modified ylides provide easy access to diverse cyclic compounds with the ability to control regioselectivity, chemoselectivity, diastereoselectivity, and enantioselectivity. Reactions using these ylides produce the structural components of many biologically active compounds and valuable intermediates in organic synthesis. Allylic telluronium and sulfonium ylides can react with alpha,beta-unsaturated esters, ketones, amides, and nitriles to afford multisubstituted vinylcyclopropanes with high selectivities. Telluronium allylides react with aromatic N-phenyl aldimines to give trans-vinylaziridines and with chiral N- tert-butylsulfinylimines to afford the optically active cis-2-substituted vinylaziridines, both with high diastereoselectivities. We also used sulfonium and telluronium allylides to prepare vinylepoxides. In addition, ylides are good reagents for the synthesis of five-membered heterocyclic compounds. By treatment of stable camphor-derived sulfur ylides with alpha-ylidene-beta-diketones, we obtained multisubstituted dihydrofurans with high diastereo- and enantioselectivities. Ammonium salts derived from cinchonidine and cinchonine react smoothly with 3-aryl and 3-heteroaryl-2-nitro acrylates, affording both enantiomers of isoxazoline N-oxides with up to 99% ee. Ylides can initiate tandem cyclizations for the synthesis of chromenes, bicyclic compounds, and cyclohexadiene epoxides. Varying the choice of base allows access to 2 H-chromenes and 4 H-chromenes from 3-(2-(bromomethyl)phenoxy)acrylates via a tandem ylide Michael addition/elimination/substitution reaction. Phosphines can catalyze an intramolecular ylide [3 + 2] annulation constructing bicyclo[ n.3.0] ring systems with three contiguous stereogenic centers. The reaction of crotonate-derived sulfur ylides with alpha,beta-unsaturated ketones affords cyclohexadiene epoxides with excellent diastereoselectivities (>99/1) in good to high yields. Using a camphor-derived sulfonium salt, we have produced asymmetric cyclohexadiene epoxides with high ee's. Overall, these results illustrate the versatility and tunability of ylides for the preparation of cyclic systems containing more than three atoms.
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