Magnesium thioesters

F. Reactions of Magnesium Thioesters and Thioamide Enoiates with... 

An example of a magnesium thioester enolate is shown in Eq. (20) [27]. These enolates were generated by reaction of thioesters with several bases, including /-PrMgCl, Et2NMgBr, and EtSMgCl. The thioester enolates were used in subsequent Claisen condensations. 

Tin(Il) shows considerable affinity towards nitrogen, therefore is expected to activate the imino group. The diastereoselective addition of tin(II) enolates derived from thioesters 1 to x-imino-esters 2 is reported12. This reaction proceeds smoothly to afford. vi w-/j-amino acid derivatives 3 (d.r. 95 5) in good yields. Lithium, magnesium, and zinc enolates do not react while titanium enolates give the adducts in low yield with preferential formation of the anti-isomer. 

Nnmerons other protocols have been developed to prepare magnesium enolates by asymmetric 1,4-addition of Grignard reagents to electron-deficient alkenes. Recently, an enantioselective metal-catalyzed version of this key reaction has been studied with enones and a, S-unsaturated thioesters Using chiral ferrocenyl-based diphosphines leads to... 

C-Acylation. C-Acylation of active methylene compounds is usually conducted under basic conditions. Masamune et al. have developed a new method for conducting this reaction under neutral conditions that is patterned on the enzymic synthesis of fatty acids. The acylating reagent is the imidazolide of a carboxylic acid (1) prepared in situ. The substrate is the neutral magnesium salt of a mono ester or thioester of a malonic acid (2), prepared with magnesium ethoxide. The reaction of 2 with 1 is conducted in THF at 25-35° for 18-24 hours the yield of products (3) is generally >85%. ... 

To a cold 0°C solution of 7V-Fmoc- or Boc-protected a-amino acid (10 mmol) and benzyl mercaptan (20 mmol, 2.48 g) in dichloromethane (30 mL) are successively added 4-(dimethylamino)pyridine (DMAP) (1 mmol, 122 mg) and 1,3-dicyclohexylcarbodiimide (DCC) (10.5 mmol, 2.17 g). After the reaction mixture is stirred overnight and the solvent removed in vacuo, ethyl acetate (100 mL) and a 1 N potassium hydrogen sulfate solution are added. The organic layer is washed with 1 N potassium hydrogen sulfate (2 X 60 mL) and saturated NaCl solution (60 mL), dried over magnesium sulfate, and filtered. The solvent is removed in vacuo and the 5-benzyl thioester is recovered as a white solid after precipitation with ether-hexane (1 1, v/v). 

Historical perspective C. H. Heathcock, Comp. Org. Syn. 2, 133-179 (1991). General review T. Mukaiyama, Org. React. 28,203-331 (1982). Application of lithium and magnesium enolates C. H. Heathcock, Comp. Org. Syn. 2, 181-238 (1991) of boron enolates B. M. Kim etal, ibid. 239-275 of transition metal enolates I. Paterson, ibid. 301-319. Stereoselective reactions of ester and thioester enolates M. Braun, H. Sacha, J. Prakt. Chem. 335,653-668 (1993). Review of asymmetric methodology A. S. Franklin, I. Paterson, Contemp. Org. Syn. 1,317-338 (1994). Cf. Claisen-Schmidt Condensation Henry Reaction Ivanov Reaction Knoevenagel Condensation Reformatskv Reaction Robinson Annulation. 

Several routes to /3-keto-acids, -esters, and -nitriles, based on the acylation of malonate derivatives, have been reported. The dianion of monoethyl malonate is acylated by acid chlorides to give -keto-esters in a one-pot synthesis,and the lithio-derivative of bis(trimethylsilyl) malonate reacts with acid chlorides, giving /3-keto-acids directly.The magnesium derivatives of monomethyl or mono-thioalkyl esters of malonic acid give j8-keto-esters or -thioesters respectively in high yield under virtually neutral conditions with acid imidazolides. Similarly, the trimethylsilyl ester of cyanoacetic acid, after lithiation, reacts with mixed anhydrides to give high yields of j8-keto-nitriles. ... 

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