A-carbonylated phosphonate

Instead of the usual 1,3-dicarbonyl compounds, heteroanalogues such as the corresponding a-carbonylated phosphonates 2-810 can also be used in the Knoevenagel/hetero-Diels-Alder process. As in the case of carbonyl groups at the... 

In the transformation of a-carbonylated phosphonate 183a and benzaldehyde 184a using a catalytic amount of piperidine as base, enol ether 88a had to be added after complete formation of the Knoevenagel product (NMR-monitoring) other-... 

Scheme 5.36. Domino-Knoevenagel-hetero-Diels-Alder reaction of a-carbonylated phosphonates 183 and a-phosphonodithioesters 187 with aromatic aldehydes 184 and enol ethers 88.

The carbanionic deprotonated phosphonate thus obtained—e.g. 14—can be reacted with a carbonyl substrate 2 just like a phosphorus ylide. However... 

An important modification to the Wittig reaction is the use of stabilized phosphonate carbanions in olefin synthesis. This reaction, originally discovered by Homer but developed by Wadsworth and Emmons, is used extensively for transformation of a carbonyl... 

Of course, the use of tris(trimethylsilyl) phosphite213 214 provides facile access to the free a-hydroxyphosphonic acids. These silyl reagents have been used for the preparation of a wide range of a-substituted phosphonates and -phosphonic acids, starting with ketene,215 a-ketophosphonates,216 ketoesters,217 218 and a,P-unsaturated carbonyl compounds,207/219-221 as well as simple aldehydes and ketones.205 210/219 224 Their use for the preparation of compounds of significant biological interest has been reviewed.125... 

Addition of trimethyl phosphite to substituted 2,5-bis(methoxy-carbonyl)cyclones provides products with addition both at the carbonyl carbon (phosphates) and at the a-carbon (phosphonates).348... 

A reaction involving phosphorus trichloride providing a free phosphonic acid apparently involves an enolized carbonyl compound as the species attacking the phosphorus.96 Methyl aromatic ketones thus provide access to the vinylicphosphonic acids (Figure 6.26). 

Method A The phosphonate (25 mmol) and the aldehyde or ketone (35 mmol) are added with stirring at room temperature to TBA-I or TBA-Br (0.27 mmol) in aqueous NaOH (50%, 20 ml) and CH2CI2 (35 ml). On completion of the reaction (the exothermic reaction with the cyano and ethoxy carbonyl compounds is complete after ca. 15 min), the organic... 

Among the various mixed trihetereo-substituted methylUthium compounds, the substitution pattern of the phosphonates 130 and 132 opens the possibility of a carbonyl aUcenylation. Thus, the reaction of 130 and 132 with aldehydes or ketones leads to the formation of dichloro- and dibromoalkenes 131 and 133, respectively (equations 66 and... 

Many newer methods for generating cyclohexane derivatives from carbohydrates still depend on the intramolecular attack of nucleophilic carbon species at electrophilic centers, and the range of options is now extensive. Thus, the nucleophiles may be carb-anions stabilized by carbonyl, phosphonate, nitro, or dithio groups, and they may bond to carbonyl carbon atoms, or to those that carry appropriate leaving groups or are contained in epoxide rings, or as jj-centers of a,p-unsaturated carbonyl systems. Otherwise, the nucleophilic activity at the 7-centers of allylsilanes or a-positions of vinyl silanes may be used to react with electrophilic carbon atoms. 

J. Seyden-Penne, Lithium Ccoordination by Wittig-Homer Reagents Formed by a-Carbonyl Substituted Phosphonates and Phosphine Oxide, Bull. Soc. Chim. Fr. 1988, 238. 

Horner-Wadsworth-Emmons reactions are C—C-forming condensation reactions between the Li, Na, or K salt of a /J-keto- or an -(alkoxycarbonyl)phosphonic acid dialkyl ester and a carbonyl compound (cf. Figure 4.41). These reactions furnish a,f)-unsaturated ketones or a j8-unsaturated esters, respectively, as the desired products and a phosphoric acid diester anion as a water-soluble by-product. In general, starting from aldehydes, the desired compounds are produced fraus-selectively or in the case of olefins with trisubstituted C—C double bonds -selectively. 

Alternatives to the standard Wittig reaction have been developed, including the Homer-Wadsworth-Emmons (HWE) reaction which involves the reaction of a phosphonate stabilized carbanion with a carbonyl compound (Scheme 2). These carbanions are generally more reactive than the traditional phosphoranes and they will often react with ketones that are unreactive to stabilized phosphoranes.2 3,8... 

If a nucleophilic addition at a carbonyl or imine carbon occurs, the product is still a phosphinate (from a phosphonous ester) or a phosphine oxide (from a phosphinous ester), but the reaction is commonly referred to as an Abramov or Pudovik reaction. An example of the Pudovik reaction is shown below (equation 16). Addition of the phosphorus nucleophile to the /3-carbon atom of an a, /3-unsaturated substrate (Michael addition) is commonly referred to as a hydrophosphinylation reaction. ... 

An almost quantitative yield was attained in a one-step synthesis when a mono-chloro derivative 89 was treated with n-butyllithium at —70°, a carbonyl compound was added, and the mixture was heated to room temperature. The procedure is also suitable for the synthesis of l-substituted-1,2-epoxyalkane phosphonates (Eq. 95). ... 

Removal of the ester Et group with Me SiBr, followed by treatment of the product (112 d) with oxalyl chloride led to the cyclic phosphonic chloride (112 e) as stereoisomeric mixture further reaction with PhSH under basic conditions gave (112 f), also as a mixture of stereoisomers. The (2 ) form of (112 f) reacted with vinylmagnesium bromide to give the 2-vinyl derivative, a step which failed, however, with the (2B) epimer. Attempts to oxidatively cleave the vinyl group and so generate a compound having a carbonyl... 

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