Enol phosphates, synthesis

Enol phosphate synthesis from a-halocaiboityls and trialkylphosphites. General scheme ... 

Erker and Trinkl synthesized the tricycles 177 as novel GABA-A/benzodiazepine receptor ligands via synthesis of enol phosphates such as 175 and reaction with isocyanides 176 (Scheme 13) <2001H1963>. 

Allylsilanes. A regio- and stereoselective synthesis of allylsilanes involves nickel-catalyzed coupling of enol phosphates with trimethylsilylmcthylmagnesium chloride... 

Marino, J. P. Abe, H. Stereospecific 1,4-addi-tions of methyl cyanocuprate to enol phosphates of ra./i-epoxycyclohexanones application to the total synthesis of ( )-a-multistria-tinj. Org. Chem. 1981, 46, 5379-5383. 

Protocol 2 produces the protected fi-formylphosphonate 12 f)-ketophospho-nates may also be synthesized by other methods,23 however, they may not be prepared in unprotected form by the Michaelis-Arbuzov reaction because the Perkow reaction, in which an a-haloaldehyde or ketone and a trialkyl phosphite yield an enol phosphate (e.g. 13, Scheme 5,24 i.e. [P—O] bond formation), competes and frequently dominates (see Section 4). Conversely halocarboxylic acid derivatives (e.g. see Table 7.1, entry 3) and acyl halides (see Protocol 3) react well in the Michaelis-Arbuzov reaction to yield useful functionalized phosphonates. fi-Ketophosphonates are useful reagents for the synthesis of a,fi-unsaturated carbonyl compounds by the Horner-Wadsworth-Emmons reaction,3,4 25 and have other applications.23... 

The synthesis of the limondd azadiradione, utiiizing a Hg° cyclization-oxidative demercuration sequence with an enol phosphate derived from trans,trans-famesol has been reported. Azadiradione, a te-tracarbocyclic memter of the iimonoid group isoiated from the neem tree, Azadirachta indica, has been converted to other tetracyclic limonoids, and is thus a key intermediate. The sequence is shown in Scheme 33. 

Sum, F.W., and Weiler, L. (1979). Stereoselective synthesis of b-substituted a, b-unsatu-rated esters by dialkylcuprate coupling to the enol phosphate of b-ketoesters. Can J Chem 57 1431-1441. 

Nigaki alcohol (18) has been identified by spectroscopic and chemical means as a constituent of Picrasma ailanthoides Planchon. Latia luciferin (19) has been synthesized in a stereoselective manner. A key step in this synthesis involves the addition of lithium dimethylcuprate to an enol phosphate derived from a 8-keto-ester to form an a,/3-unsaturated ester. Dehydro-/8-ionilideneacetic acid (20), an important intermediate in the synthesis of abscisic acid, has been prepared, as have the two nor-abscisic acid derivatives (21). The metabolite (22) of abscisic acid has been identified in the seeds of Robinia pseudacacia... 

Cyclization. Treatment of the unsaturated enol phosphate ester 1 with 1 equiv. of mercury(II) trifluoroacetate in nitromethane at 0° followed by aqueous sodium chloride produced the mercurated bicyclic keto ester 2 in 60% yield along with 20% of the monocarbocyclic product 3. Keto ester 2 is an intermediate in a total synthesis of aphidicolin (4). This reaction is the first example of the use of a mercury(II) salt tor simultaneous construction of two carbocyclic rings. ... 

A similar synthesis of alkynes by reductive elimination of enol phosphates of /3-oxosulfones with sodium in liquid ammonia has been reported. ... 

Highly reactive metallic titanium, prepared from TiCb and potassium, reduces enol phosphates to alkenes, permitting regioselective synthesis of dienes from a,p-unsaturated ketones. ... 

A new cyclising reagent is proposed for the synthesis of 5-unsubstituted 1,3,4-thiadiazoles (133). The latter are formed in good yield by the reaction of thiohydrazides (134) with diethyl chlorophosphate (Scheme 39). A useful, one-pot protocol has been developed for the conversion of enolizable ketones (135) to alkylated or arylated olefins (136) by Pd-catalysed cross coupling of in-situ generated enol phosphates (137) with Grignard reagents (Scheme 40). ... 

Both the enol phosphate method, and the reduction of the keto sulfone to the p-hydroxy sulfone followed by reductive cleavage to produce ( )-alkenes, have been applied to the synthesis of brefeldin A. Gais and cowoikers added the sidfone (462) to the lactone (461), formed the enol phosphate and reduced with sodium and ammonia to the ( )-alkene (463), in a 65% overall yield (equation 107). ... 

A mild and efficient synthesis of terminal alkynes starts with readily accessible methyl ketones and converts them to the corresponding enolates with LDA. The eno-lates produced are trapped with diethyl chlorophosphate to give enol phosphates, which possess a good leaving group for elimination. Subsequent treatment of the enol phosphates with LDA furnishes the corresponding lithium alkynylides and on protonation of these, the corresponding terminal acetylenes. 

A connective synthesis of alkynes inspired by the Julia alkenation was developed by Lythgoe and coworkers for the synthesis of la-hydroxy vitamin D3, as shown in Scheme 34. The P-keto sulfone (101) derived by condensation of the the metalated sulfone (99) with the ester (100) was converted to the enol phosphate (102), which on reductive elimination gave the enynene (103). 

The precise conditions for the reductive elimination are important. Use of Na(Hg) in THF-MeOH or THF alone gives messy reactions, owing to substantial cleavage of the P—O bond of the enol phosphate but this can be avoided with Na(Hg) in THF-DMSO. Alternatively, Na in liquid ammonia can be used to effect the reductive elimination but the reaction must be very carefully controlled in order to avoid reduction of the alkyne to a tra/ii-alkene. A deliberate over-reduction of the initial alkyne product to an alkene was used in a synthesis of the intermediate (104) in a synthesis of brefeldin (Scheme 35). ... 

Reactions of cycloalkadiene monoepoxides have received considerable attention. In general, cyanocu-prates have provided better Sn2 selectivity than lithium homocuprates, and the alternative Sn2 reaction is more competitive with vinyl- or phenyl-cuprates than with alkylcuprate reagents. Reactions of cy-clopentadiene monoepoxides with cyanocuprates have found application in prostaglandin synthesis. Effective electrophilic a -alkylation of cyclic enones can be accomplished by Sn2 cuprate addition to the corresponding epoxy enolate, enol phosphate or silyl enol ether. ... 

A new synthesis of olefins involves carbon-oxygen bond cleavage in enol phosphates, e.g. (69), with lithium copper reagents. ... 

Because heteroatom-substituted vinylphosphonates such as enol phosphates and vinyl halides are masked acetylenic compounds, a variety of methods have been developed for their elaboration and subsequent use in the synthesis of dialkyl 1-alkynylphosphonates. These eliminations usually have the leaving group P to the phosphoryl group, although cases in which the leaving group is a to the phosphorus center are also known (Scheme 1.12). 

Gaydou, E.M., Freze, R., and Buono, G., Enol phosphates. Part 5. Synthesis and physical properties of substituted phosphates. Bull. Soc. Chim. Fr, 2279, 1973. 

Hammond, G.B., Calogeropoulou. T., and Wiemer, D.F., The 1,3-migration of phosphorus from oxygen to carbon. A new synthesis of P-ketophosphonates from enol phosphates. Tetrahedron Lett.. 27, 4265, 1986. 

A word about the synthesis of the a-series, a-geraniol (73) and a-nerol (74), is warranted because they are often intermediates in the synthesis of 1-hydroxylated compounds (e.g., some diols described below). Weiler has continued his exploitation of the dianion of methyl acetoacetate to this end. Instead of prenylation (Vol. 4, p. 461, Ref. 73) he carried out a similar series of operations by alkylating the dianion with 4-bromo-2-methyl-l-butene, thus arriving at compounds of the a-series via the keto ester 75, methylating the enol phosphate to 76. He also prepared the double methylene isomer 77 (R = COEt) of geranyl propionate from the intermediate 75. The purpose of synthesizing this propionate was to prepare the pheromone of the San Jose scale, Quadraspidiotus pernicious, which is a mixture of the propionates of 73, 74,... 

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