Enol phosphate coupling

The coupling reaction between lithium dimethylcuprate and acyclic enol phosphates must be carried out between -47 and -98 C for stereoselective formation of g-methyl-a,g-unsaturated esters. 

This procedure illustrates a new method for the preparation of 6-alkyl-a,g-unsaturated esters by coupling lithium dialkylcuprates with enol phosphates of g-keto esters. The procedure for the preparation of methyl 2-oxocyclohexanecarboxylate described in Part A Is based on one reported by Ruest, Blouin, and Deslongcharaps. Methyl 2-methyl-l-cyc1ohexene-l-carboxylate has been prepared by esterification of the corresponding acid with dlazomethane - and by reaction of methyl 2-chloro-l-cyclohexene-l-carboxyl ate with lithium dimethylcuprate. -... 

The formation of g-alkyl-a,g-unsaturated esters by reaction of lithium dialkylcuprates or Grignard reagents in the presence of copper(I) iodide, with g-phenylthio-, > g-acetoxy-g-chloro-, and g-phosphoryloxy-a,g-unsaturated esters has been reported. The principal advantage of the enol phosphate method is the ease and efficiency with which these compounds may be prepared from g-keto esters. A wide variety of cyclic and acyclic g-alkyl-a,g-unsaturated esters has been synthesized from the corresponding g-keto esters. However, the method is limited to primary dialkylcuprates. Acyclic g-keto esters afford (Zl-enol phosphates which undergo stereoselective substitution with lithium dialkylcuprates with predominant retention of stereochemistry (usually > 85-98i )). It is essential that the cuprate coupling reaction of the acyclic enol phosphates be carried out at lower temperatures (-47 to -9a°C) to achieve high stereoselectivity. When combined with they-... 

Coupling of enolphosphates and alkylaluminum compounds. Enol phosphates and RjAl couple in the presence of 3 mole % of this Pd(0) complex to give alkcncs with retention of configuration. 

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

Cahiez and Avedissian further reported the cross-coupling reaction of cheap and easily available enol phosphates [10]. These substrates are less reactive, which explains the higher catalyst loadings and 2 equiv. of Grignard reagent are required (Scheme 5.5). 

Scheme 5.5 Iron-catalyzed cross-coupling reaction of an enol phosphate reported by Cahiez and Avedissian.

The aryl and enol triflates 306 and 307 couple with Me3Al, Et3Al and BU3AI [136], The enol phosphate 309, derived from ketone 308, is displaced with methyl group of Me3Al using Pd catalyst in dichloroethane. Based on this reaction, 4-tert-butylcyclohexanone (308) is converted to 2-methyl-5-tert-butylcyclohexanone (311) via 310 [137],... 

Instead of enol triflate, the enol phosphate 334, derived from lactone 333, is used for the coupling to afford the cyclic enol ether 335. No coupling of phenyl phosphate... 

In the presence of a Pd catalyst prepared from l d(OAc), and (o-CHjQHj), (4 equiv.), 1 converts enol phosphates into vinylsilanes. Higher yields are usually obtained for this coupling with a related organomagnesium reagent, QHjICHOiSiMgCH, (2), prepared in situ from QH CHOiSiLi and CH,Mgl. 

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. 

Coupling with the enoi phosphate of fi-keto esters. The coupling of lithium dialkylcuprates with enol phosphates of ketones (7,93) is also possible with enolates... 

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). ... 

Because of the very high price of ATP, reaction (5.7) must be coupled with a regenerating system, the transfer of phosphate to ADP starting from the enol phosphate of pyruvic acid (an easily accessible and inexpensive phosphate), catalysed by the enzyme pyruvate kinase (reaction (5.8). In the same flask are mixed glucose, phosphoenolpyruvate, hexokinase, pyruvate kinase, and a catalytic quantity of ATP (about 1% mol) and the system produces D-glucose 6-phosphate until the phosphoenolpyruvate runs out. The kinases are easily accessible and, if they are immobilized on an insoluble support (see Section 10.4.1), they are reusable a certain number of times. In this way glucose 6-phosphate can be easily prepared on a 250 g scale (Poliak et al. 1977). 

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