DIETHYL S- -MALATE

Seebach, D. Aebi, J. Wasmuth, D. Diastereo-selective a-alkylation of / -hydroxycarboxylic esters through alkoxide enolates diethyl (2S,3R)-(+)-3-allyl-2-hydroxysuccinate from diethyl (S)-(-)-malate. Org. Synth. 1990, Coll. Vol. VII, 153-159. 

DIASTEREOSELECTIVE a-ALKYLATION OF g-HYDROXYCARBOXYLIC ESTERS THR0U6H ALKOXIDE ENOLATES (+)-DIETHYL (2S,3R)-3-ALLYL-2-HYDROXYSUCCIMATE FROM (-)-DIETHYL S-MALATE (Butanedlolc acid, 2-hydroxy-3-(2-propenyl)-, diethyl ester, [S-(R,S)])... 

Another interesting approach to the less readily accessible diethyl ( S)-malate (3) is enan-tioselective bioreduction of sodium diethyl oxalacetate (4) with baker s yeast Saccharomyces cerevisiae). Under fermenting conditions, 3 is produced in high yield with >98% ee [10]. 

Diethyl ( S)-malate (3) is readily acetylated with acetic anhydride in pyridine to give diethyl (5)-acetoxysuccinate (6) in good yield [7]. 

Malate esters are easily reduced in a highly selective fashion using either diborane [40,41] or borane—methyl sulfide complex [42— 45] in the presence of a catalytic amount of sodium borohydride (5 mol%) to give diol esters 45. Yields of 45a and 45b generally range from 80-97%, while 45c is formed in 60% yield [46]. Dimethyl (5)-malate is reduced with 99 1 selectivity as regards C-1 to C-4 ester reduction, while diethyl ( S)-malate shows even greater selectivity (200 1). 

Doubly deprotonated dimethyl or diethyl ( S)-malate is readily generated at — 78 °C with 2.2 equivalents of LDA. Subsequent addition of an alkyl halide produces anti 3- lkyl malates (225) with diastereoselectivities in excess of 90%. Better results are obtained using LiHMDS as the base [82]. The 3-benzyl derivative 225c can be isolated in 70% yield with >35 1 diastereoselectivity. 

In the synthesis of (— )-<5-multistriatin (453), alkylated diethyl ( S)-malate (225b) is converted to the tosyl acetonide 450 by the sequence of reactions described previously in this... 

The Seebach aglycone synthesis is also independently based on the aldol coupling of the dialdehydic diolide 282 and the ethyl ketone 288, which are prepared by the use of chiral building blocks, Roche ester 285 or diethyl (S)-malate (286) and ethyl (R)-3-hydroxybutyrate (287). 

DIETHYL (2S,3R)-3-ALLYL-2-HYDROXYSUCCINATE FROM (-)-OIETHYL S-MALATE... 

Dimethyl maleate Sipomer DMM 210-852-7 Amyl propionate Ucar n-Pentyl Propionate 210-871-0 Methyl disulfide 210-930-0 Diethyl DL-malate 210-937-9 Di-s-butylamine 210-953-6... 

Triol 370 can also be prepared by reduction of EE-protected dimethyl malate 9a [14,15] or diethyl malate 9b [16] to give (5)-2-(l-ethoxyethoxy)-1,4-butanediol (371) in high yield. Deprotection under acidic conditions then furnishes 370 (Scheme 49). Cyclization of 370 (obtained by this route) under acidic conditions results in the formation of ( S)-( + )-3-... 

Both enantiomers of 4-iodo-1,2-epoxybutane are available from ( S)-malic acid as shown in Schemes 57 and 58. Reduction of THP-protected dimethyl or diethyl malate with lithium aluminum hydride gives diol 417. Immediate mesylation affords 418 in 65—70% overall yield [6,19]. Acidic hydrolysis of the THP ether furnishes the crystalline bis-mesylate 419, which upon mild base treatment cyclizes to epoxide 420 with retention of configuration. Treatment with sodium iodide gives (5)-( — )-4-iodo-1,2-epoxybutane (421). 

S)-diethyl malate. Various optically active 3,3-dialkyl... 

Ganguly, S. Roundhill, D.M. (1993) Catalytic hydration of diethyl maleate to diethyl malate using divalent complexes of palladium(ll) as catalysts, Organometallics, 12, 4825-32. 

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