Horner-Wadsworth-Emmons asymmetric

The catalytic asymmetric Horner-Wadsworth-Emmons reaction was realized by use of the quaternary ammonium salts 7 derived from cinchonine as a phase transfer catalyst.1631 Thus, tert-butylcyclo-hexanone 85 reacted with triethyl phosphonoacet-ate 86 together with RbOH-H20 in the presence of the ammonium salts 7, and then the product 87 was isolated after reesterification by treatment with acidic ethanol, as shown in Scheme 27 Among the... 

Scheme 27. Asymmetric Horner-Wadsworth-Emmons reaction.

S. Arai, S. Hamaguchi, T. Shioiri, Catalytic Asymmetric Horner-Wadsworth-Emmons Reaction under Phase-Transfer-Catalyzed Conditions , Tetrahedron Lett 1998, 39,2997-3000. 

Asymmetric Horner-Wadsworth-Emmons and Related Reactions... 

An asymmetric Horner-Wadsworth-Emmons reaction has been developed which uses an external chiral ligand to avoid the need to prepare chiral phosphonate derivatives. ... 

Scheme 8 summarizes the introduction of the missing carbon atoms and the diastereoselective epoxidation of the C /C double bond using a Sharpless asymmetric epoxidation (SAE) of the allylic alcohol 64. The primary alcohol 62 was converted into the aldehyde 63 which served as the starting material for a Horner-Wadsworth-Emmons (HWE) reaction to afford an E-configured tri-substituted double bond. The next steps introduced the sulfone moiety via a Mukaiyama redox condensation and a subsequent sulfide to sulfone oxidation. The sequence toward the allylic alcohol 64 was com-... 

The asymmetric Horner-Wadsworth-Emmons (HWE) reaction of l,3-dioxan-5-ones with phosphonate 184 and a chiral diamine was reported. With the /i r/-butyl-substituted l,3-dioxan-5-one, the product possesses a chiral axis. It was obtained in good yield and with 80% ee (Scheme 53) <2002TL281>. The HWE reaction with similar heterocyclic substrates was used to provide conformationally restricted arachidonic acid derivatives <1999TA139>. 

Shibasaki made several improvements in the asymmetric Michael addition reaction using the previously developed BINOL-based (R)-ALB, (R)-6, and (R)-LPB, (R)-7 [1]. The former is prepared from (R)-BINOL, diisobutylaluminum hydride, and butyllithium, while the latter is from (R)-BINOL, La(Oz -Pr)3, and potassium f-butoxide. Only 0.1 mol % of (R)-6 and 0.09 mol % of potassium f-butoxide were needed to catalyze the addition of dimethyl malonate to 2-cy-clohexenone on a kilogram scale in >99% ee, when 4-A molecular sieves were added [15,16]. (R)-6 in the presence of sodium f-butoxide catalyzes the asymmetric 1,4-addition of the Horner-Wadsworth-Emmons reagent [17]. (R)-7 catalyzes the addition of nitromethane to chalcone [18]. Feringa prepared another aluminum complex from BINOL and lithium aluminum hydride and used this in the addition of nitroacetate to methyl vinyl ketone [19]. Later, Shibasaki developed a linked lanthanum reagent (R,R)-8 for the same asymmetric addition, in which two BINOLs were connected at the 3-positions with a 2-oxapropylene... 

Cyclopropanation, Horner-Wadsworth Emmons Reaction, and Darzens Condensation Although induction in the cyclopropanation of alkenes was reported early, this work was disputed [49]. Other reports of cyclopropanations have yielded, at best, low asymmetric inductions [llh,50]. The first example of a catalytic asymmetric Horner-Wadsworth Emmons reaction, which is promoted by a chiral quaternary ammonium salt, was reported recently by the Shioiri group (Scheme 10.10) [51]. The reaction of the prochiral ketone 74 gives optically active a,P-unsaturated ester 76 with 57% ee. 

The first example of a catalytic asymmetric Horner-Wadsworth-Emmons reaction was recently reported by Arai et al. [78]. It is based on the use of a chiral quaternary ammonium salt as a phase-transfer catalyst, 78, derived from cinchonine. Catalytic amounts (20 mol%) of organocatalyst 78 were initially used in the Homer-Wadsworth-Emmons reaction of ketone 75a with a variety of phospho-nates as a model reaction. The condensation products of type 77 were obtained in widely varying yields (from 15 to 89%) and the enantioselectivity of the product was low to moderate (< 43%). Although yields were usually low for methyl and ethyl phosphonates the best enantioselectivity was observed for these substrates (43 and 38% ee, respectively). In contrast higher yields were obtained with phosphonates with sterically more demanding ester groups, e.g. tert-butyl, but ee values were much lower. An overview of this reaction and the effect of the ester functionality is given in Scheme 13.40. 

For reviews about the asymmetric Horner-Wadsworth-Emmons reaction, see (a) T. Rein, L. Vares,... 

For selected asymmetric Horner-Wadsworth-Emmons reactions using stoichiometric amount of a chiral auxiliary, see (a) B. M. Trost, D. P. Curran,/. Am. Chem. Soc. 1980, 102, 5699-5700 (b) S. Hanessian, S. Beaudoin, Tetrahedron Lett. 1992, 33, 7659-7662 (c) N. Kann, T. Rein,... 

Starting from (+)-diethyl tartrate (2), bromobutenolide 18 was obtained in nine steps. Three of the four C=C double bonds were built up using a Wittig reaction (11—>12), an Ando- y Q Horner-Wadsworth-Emmons reaction (13— 15) and (3-elimination (16 18). From (-)-actinol (3) stannane 23 and sulfone 24 were synthesized in 9 and 13 steps, respectively. Their common intermediate, alkyne 22, was synthesized using methoxycarbonylation. Sharpless asymmetric epoxidation and Ci-elongation with lithio trimethylsilyldiazomethane. Stannane 23 was obtained upon hydrostannylation and TBS deprotection. Sulfone 24 was obtained after addition to methyl tetrolate, reduction, Mukaiyama redox condensation, acetylation and catalytic oxidation. 

Yamaguchi, M., Hirama, M. Kinetic resolution of racemic aldehydes and ketones by the asymmetric Horner-Wadsworth-Emmons reaction. Chemtracts Org. Chem. 1994, 7,401-405. 

Rein, T., Vares, L., Kawasaki, I., Pedersen, T. M., Norrby, P.-O., Brandt, P., Tanner, D. Asymmetric Horner-Wadsworth-Emmons reactions with meso-dialdehydes scope, mechanism, and synthetic applications. Phosphorus, Suifur Siiicon Reiat. Bern. 1999, 144-146, 169-172. 

Kellogg, R. M. Enantioconvergent synthesis by sequential asymmetric Horner-Wadsworth-Emmons and palladium-catalyzed allylic substitution reactions. Chemtracts 2002, 15, 69-73. 

Parallel kinetic resolution is a developing area of asymmetric synthesis which facilitates the simultaneous conversion of both enantiomers of a racemic mixture into useful products. Pedersen and co-workers have recently reported the first Horner-Wadsworth-Emmons procedure that allows the parallel kinetic resolution of racemic aldehydes. 

The enantioselective desymmetrization of prochiral ketones of the type 46 by means of the Horner-Wadsworth-Emmons reaction is an elegant approach to the synthesis of the enantioenriched enone products 47. Enones such as 47 bearing a remote stereogenic center are difficult to prepare by other methods. The first catalytic asymmetric Horner-Wadsworth-Emmons reaction was realized by using cinchona-based PTCs as organocatalysts [40]. Up to 55-57% ee values and satisfactory yields were obtained using catalytic amounts (20 mol%) of the N-benzylcinchoninium salts 48 and RbOH as a base (Scheme 11.25). 

Gais, H.-J., Schmiedl, G., and Ossenkamp, R.K.L., Total synthesis of (-i-)-3-oxacarbocyclin. Part 1. Retrosynthesis and asymmetric olefination through Horner-Wadsworth-Emmons, Peterson and Martin reactions, Liebigs Ann., 2419, 1997. 

Aral and Shioiri reported the first example of a catalytic asymmetric Horner-Wadsworth-Emmons (HWE) reaction promoted by chiral PTC catalyst 7a, which gives optically active a,(3-unsaturated esters 107 (57% enantiomeric excess). Although the enantioselectivity was not satisfactory, the results suggested a significant possibility that PTC catalysis can mediate various asymmetric conversions (Scheme 16.39). ... 

As a direct route for the constructing carbon-carbon bonds, catalytic asymmetric Michael additions with various carbon-based nucleophiles including malonic esters, cyanide, electron-deficient nitrile derivatives, a-nitroesters, nitroalkanes, Horner-Wadsworth-Emmons reagent, indoles, and silyl enol ethers have attracted considerable attention. 

Scheme 19.28 Asymmetric Michael addition of a Horner-Wadsworth-Emmons reagent to q clic enones catalysed by ALB.

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