Asymmetric tandem wittig rearrangement/Aldol reactions.

A new method for the asymmetric synthesis of alpha-alkyl-alpha,beta-dihydroxy esters that involves tandem Wittig rearrangement/aldol reactions of O-benzyl- or O-allylglycolate esters derived from 2-phenylcyclohexanol is described. This sequence constructs two C-C bonds and two stereocenters, one of which is quaternary, to afford syn diol products with excellent stereocontrol. Cleavage of the chiral auxiliary affords enantiomerically enriched products with up to 95% ee. The application of this method to the preparation of a key intermediate in the synthesis of the antifungal agent alternaric acid is also described.

[1]  O. Bedel,et al.  Is osmylation always preferring the richest double bond , 2008 .

[2]  Andreas Ide,et al.  Enantioselective equilibration-access to chiral aldol adducts of mandelic acid esters. , 2006, Organic letters.

[3]  J. Wolfe,et al.  Tandem Wittig rearrangement/aldol reactions for the synthesis of glycolate aldols. , 2006, Organic letters.

[4]  Isamu Shiina,et al.  Total synthesis of buergerinin F via effective construction of the asymmetric quaternary carbons using an enantioselective aldol reaction. , 2005, Chemical communications.

[5]  N. Pastori,et al.  Reactivity of methyl mandelate-Ti(IV)-enediolate: oxidative homocoupling versus aldol and direct Mannich-type syn-diastereoselective condensation. , 2005, The Journal of organic chemistry.

[6]  L. Truesdale,et al.  Synthesis of (+)‐(1S,2R)‐ and (−)‐(1R,2S)‐trans‐2‐Phenylcyclohexanol Via Sharpless Asymmetric Dihydroxylation (AD) , 2003 .

[7]  S. Matsunaga,et al.  Direct catalytic asymmetric Michael reaction of hydroxyketones: asymmetric Zn catalysis with a Et2Zn/linked-BINOL complex. , 2003, Journal of the American Chemical Society.

[8]  Susumu Kobayashi,et al.  Stereocontrolled preparation of 1,2-diol with quaternary chiral center , 2002 .

[9]  M. Andrus,et al.  ChemInform Abstract: Highly Selective syn Glycolate Aldol Reactions with Boron Enolates of Masamune Norephedrine Esters. , 2001 .

[10]  B. Crousse,et al.  Novel [1,2]- and [2,3]-Wittig rearrangements of alpha-benzyloxy beta-CF(3)-beta-lactam enolates. , 2001, Organic letters.

[11]  L. Paquette,et al.  Base-promoted 1,2-shifts in α-benzyloxy ketones , 1999 .

[12]  B. Trost,et al.  Ruthenium-Catalyzed Alder Ene Type Reactions. A Formal Synthesis of Alternaric Acid , 1998 .

[13]  K. Tomooka,et al.  Recent developments in the [1,2]-Wittig rearrangement , 1997 .

[14]  Jifeng Liu,et al.  The Anti-Selective Boron-Mediated Asymmetric Aldol Reaction of Carboxylic Esters , 1997 .

[15]  A. Ichihara,et al.  Total Synthesis and Stereochemistry of Alternaric Acid , 1994 .

[16]  Hisashi Yamamoto,et al.  Highly selective generation and application of (E)- and (Z)-silyl ketene acetals from .alpha.-hydroxy esters , 1993 .

[17]  Isamu Shiina,et al.  Enantioselective synthesis of the α-hydroxy-α-methyl-β-hydroxy units via asymmetric aldol reaction , 1993 .

[18]  D. Curtin,et al.  Cleavage and Rearrangement of Ethers with Bases. III. Ethers of Benzoin and Ethyl Mandelate1a , 1954 .

[19]  P. W. Brian,et al.  Alternaric acid; a biologically active metabolic product of Alternaria solani (Ell. & Mart.) Jones & Grout; its production, isolation and antifungal properties. , 1951, Journal of general microbiology.