Homer-Wadsworth-Emmons reagent

Wittig/Homer-Wadsworth-Emmons reagents on a PEG support (Table 8, entry 25) [477] ... 

Kann, N., Rein, T.. Akermark. B., and Helquist, P., New functionalized Homer-Wadsworth-Emmons reagents. Useful building blocks in the synthesis of polyunsaturated aldehydes. A short synthesis of ( )-( , )-coriolic acid.. 1. Org. Chem., 55, 5312, 1990. 

A modified Homer-Wadsworth-Emmons reagent with high Z stereoseiectivity using trifluoroethyl phosphonates in reaction with saturated, unsaturated or aromatic aldehydes. 

Other simple reagents for the rapid synthesis of conjugated dienic esters are the vinylogous Homer-Wadsworth-Emmons reagents, known for a while and employed for instance for a total synthesis of Efomycine M [111]. This family of reagents has recently been extended to branched allylic phosphonates such as 123, opening up access to 4-methyldienoates 125 (Scheme 57) [112]. 

Homer-Wadsworth-Emmons reactions of ketones and aldehydes with phosphono-acetate esters, (R20)2P(=0)CH2C02R1, produce E/Z mixtures of a, /Tunsaturated esters. Use of the conventional reagent, sodium hydride, gives some selectivity. The combination of tin(II) triflate and A -cthylpipcndine enhances—and sometimes also reverses—the selectivity in most cases studied.71 Six-membered oxo-coordinated tin intermediates are proposed to control the selectivities observed. A similarly selective synthesis of trisubstituted exocyclic alkenes from cyclic ketones has been reported.72... 

When the substituent becomes very anion-stabilising, as in 42, the ylid may not react with ketones and anions of phosphonate esters are usually preferred in the Homer-Wadsworth-Emmons (HWE) variant.11 The reagent triethyl phosphonoacetate 46 is made by combining a phosphite (EtO)3P instead of a phosphine, with ethyl bromoacetate. Displacement of bromide 44 gives a phosphonium ion that is dealkylated by bromide 45. 

Condensations between aldehydes and metalated phosphonic acid dialkyl esters other than those mentioned previously are also referred to as Homer-Wadsworth-Emmons reactions. Nevertheless, in these esters, too, the carbanionic center carries a substituent with a pi electron withdrawing group, for example, an alkenyl group, a polyene or a C=N group. The Homer-Wadsworth-Emmons reactions of these reagents are also stereoselective and form the new C=C double bond /ra/ ,v-selectively. 

The effectiveness of dialkyl 1-aIkynylphosphonates as acelonyl equivalents for the preparation of dialkyl 2-oxoalkylphosphonates has long been established. Because 2-oxoaIkylphosphonates themselves are versatile synthetic intermediates, especially as the reagents of choice for promoting a number of Homer-Wadsworth-Emmons cyclization reactions, procedures that effect the direct conversion of dialkyl 1-alkynylphosphonates into dialkyl 2-oxoalkylphosphonates are of special importance. The procedure for the hydration of dialkyl 1-alkynylphosphonates has remained unchanged since the first report in 1966 (Scheme 1.21). Thus, treatment of diethyl 1-alkynylphosphonates with aqueous H2SO4 in MeOH in the presence of HgSO4 gives, after reflux for 15 h - ... 

The readily available diethyl 2-cyano-2-(trimethylsilyl)ethylphosphonate appears to be an attractive reagent for the synthesis of 2-cyano-l,3-butadienes. Their formation combines the Peterson and Homer-Wadsworth-Emmons reactions in a one-pot process. The reaction has been developed with a variety of aldehydes, and the yields are generally high (34-89%, Scheme 2.38). ... 

Subsequently, the nucleophilic chlorination of oc-hydroxyphosphonates has become one of the most important routes for the synthesis of a-chlorophosphonates (Scheme 3.15). A wide variety of chlorinating agents has been employed, some of which are presented in Table 3.4. Two couples, CCiyPPhj and POClj/PhNEtz, seem to give the best results, with the latter being more easily removed from the reaction mixture. The a-chlorophosphonates are important reagents for the preparation of chloroalkenes and alkynes, which are obtained after Homer-Wadsworth-Emmons reactions with carbonyl compounds. 

The same strategy has been used to prepare trans bicyclic enones. The protected C5 phosphonylated aldehyde is obtained in 84% yield by a CuBr SMe2-mediated Michael addition of the Grignard reagent derived from 4-chlorobutyraldehyde diethyl acetal to a 5-phosphonylated 2,3-dihydro-4-pyridone in THF. Subsequent room-temperature hydrolysis of the acetal using aqueous oxalic acid in THF affords a near-quantitative yield of the crude aldehyde, which undergoes an intramolecular Homer-Wadsworth-Emmons reaction under treatment with Et3N/LiCl in THF at room temperature (89%). ... 

The stabilized a-substituted cyanomethylphosphonate carbanion resulting from the addition of potassium diethyl cyanomethylphosphonate to one equivalent of acrylonitrile in THF/HMPA appears to be a useful reagent in Homer-Wadsworth-Emmons olefination reaction. Thus, the reaction with aromatic aldehydes is completely stereoselective and produces ( )-l-aryl-2,4-dicyano-1-butenes in high yields (71-83%, Scheme 6.34).- ... 

Because dialkyl 2-oxo-(0-(alkoxycarbonyl)alkylphosphonates are valuable synthetic intermediates that may be either converted to die corresponding amino compounds or treated with a variety of carbonyl compounds in a Homer-Wadsworth-Emmons reaction,procedures that effect their preparation are of special importance. The Michaelis-Arbuzov reaction, which furnishes low yields, does not appear to be an appropriate method for the preparation of dialkyl 2-oxo-(fl-(alkoxycarbonyl)alkylphosphonates. One of the most attractive synthetic methods involves the chemoselective reaction of a-metallated dialkyl alkylphosphonates with acylating reagents such as carboxylic acid chlorides, cyclic anhydrides, or esters. 

Rubottom oxidation reactions have been conducted on enolsilanes derived from a number of different carbonyl derivatives including carboxylic acids and esters.15 For example, the Rubottom oxidation of bis(trimethylsilyl)ketene acetal 30 provided a-hydroxy carboxylic acid 31 in 81% yield. Use of alkyl trimethylsilyl ketene acetal substrates generates a-hydroxy esters, as seen in the conversion of 32 to 33.16 The synthesis of 3-hydroxy-a-ketoesters (e.g., 36) has been accomplished via Rubottom oxidation of enolsilanes such as 35 that are prepared via Homer-Wadsworth-Emmons reactions of aldehydes and ketones with 2-silyloxy phosphonoacetate reagent 34.17 The a-hydroxylation of enolsilanes derived from P-dicarbonyl compounds has also been described, although in some cases direct oxidation of the P-dicarbonyl compound is feasible without enolsilane formation.18... 

After protection of the alcohol function, the carbonyl group is converted into a methylene group by means of the Tebbe reagent, followed by a Swern oxidation and a Homer-Wadsworth-Emmons reaction. 

There are many carbanion and ylid derivatives that also contain an acid moiety, an ester or an acid sutrogate. Ester and acid enolates, for example, react with a variety of electrophilic reagents to produce new acid or ester derivatives. If the electrophile contains an amine or an amine surrogate, amino acids are produced as the final product. In addition, ylids bearing an acid or ester moiety react with aldehydes or ketones bearing an amine moiety via a Wittig reaction or a Homer-Wadsworth-Emmons reaction to give alkenyl amino acids. 

---