Phosphine Oxides and Phosphonate Esters

Phosphine Oxides and Phosphonate Esters. Many extensions of the Wittig reaction have been introduced that improve or modify the reactivity and/or stereoselectivity of the ylid. Horner et al. showed that a-lithiophosphine oxides such as that derived from 552 react with aldehydes or ketones to give a p-hydroxy phosphine oxide (553) as an isolable species. Subsequent treatment with base liberates the alkene, (554). Wadsworth and Emmons modified the Horner reaction to use phosphonate ester derivatives such as 

Reaction with aldehydes or ketones (such as benzaldehyde) in the presence of base gave the olefination product 556 (in 84% yield).502 These variations have come to be called the Horner-Wadsworth-Emmons modiflcation of the Wittig reaction, or Horner-Wadsworth-Emmons olefination.503 It is sometimes called Horner-Emmons olefination. 

The major product of olefination with phosphonate carbanions is usually the ( )-isomer.304 However, a (Z)-selective reaction has recently been developed that uses sodium iodide and DBU as the base.305 Speziale and Ratts suggested that increased amounts of (Z) alkene were obtained by increasing the steric bulk of the L and l1 groups in 557 and 560, formed by reaction of the phosphonate ester ylid with a carbonyl compound. This equilibrium favors the anti conformation(557 over 560 and elimination gives more of the (Z) product, 559.306 jjjjg model assumes that steric encumbrance is more important in 557 and 560 than in oxaphos-phetanes 558 and 561, respectively, that are required for syn elimination to the alkene. This equilibrium generally favors 559 over 562 due to the stereochemical preferences in the initially formed ylid products. 

2equivNEt3. no NEt3 added. % 565 after a reaction time of 24 h. 

Intramolecular olefination reactions are possible using phosphonate carbanions because they are relatively stable. This type of cyclization is also possible with Wittig reagents, but it is more facile with phosphonate carbanions. One example is Weinreb s treatment of phosphonate 571 with potassium carbonate and a crown ether to give a 84% yield of 572 in a synthesis of phyllanthine.50 

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Similar palladium-catalyzed cascade arylations also occur with acyclic alkenes, including a,p-unsaturated sulfones (Equation 19.153), sulfonamides, phosphine oxides, and phosphonate esters. In contrast, typical conjugated olefins, such as a, 3-unsaturated esters and enones almost exclusively react to form products from Heck reactions. Direct arylations have also been conducted with disubstituted alkynes containing a terminal arene and a large group, such as an aryl or ferf-butyl group (Equation 19.154). ... 

Alonso E, Alonso E, Solis A et al (2000) Synthesis of iV-alkyl-(a-aminoalkyl) phosphine oxides and phosphonic esters as potential HlV-protease inhibitors, starting from a-aminoacids. Synlett 2000 698-700... 

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