Dimenthyl -: 1,2-Cyclopropane

Chiral 1,2-cycloalkanedicarboxylic acids.1 This ring system can be obtained by coupling 1,co-dihalides or -ditosylates with the dienolate of d- or /-menthyl succinate (1). The dienolate generated with lithium 2,2,6,6-tetramethylpiperidide is mainly the (E,E)-isomer, whereas deprotonation with LDA and HMPT generates mainly the (Z,Z)-isomer. Thus reaction of 1 (R = /-menthyl) with LiTMP in THF at -78° with CH2BrCl results in (S,S)-( - )-dimenthyl cyclopropane-frww-1,2-dicarboxylate (2) in 58% chemical yield and 99% de. A similar reaction of 1, R = d-menthyl, results in (R,R)-2 in 60% yield and 80% de. 

Condensation of (-)-Dimenthyl Succinate Dianion with 1, u-Dihalides (-)-Dimenthyl Cyclopropane-(lS,2S)-1,2-dicarboxylate... 

Enantioselective cyclopropanation. The reaction of dimenthyl fumarates (2) with isopropylidene(triphenyl)phosphorane proceeds in 74% de in THF at -78 — 20°. (1S,3S)-3 is obtained when the /-menthyl group is used inductor (lR,3R)-3 is obtained in the same optical yield when the unnatural //-menthyl group is used. The concentration plays an important role enantioselectivity is increased by dilution and decreased by concentration. 

C. (+)-(lS,2S>-Cyolopvopane-ljZ-diBarboxylio aoid. (-)-Dimenthyl (lS,2S)-cyclopropane-l,2-dicarboxylate (4.06 g, 10 mmol, +17.8°) Is dissolved in 20 ml of a 10% potassium hydroxide solution in 9 1 methanol/water In a 50-mL, one-necked, round-bottomed flask equipped with a magnetic stirring bar. The solution is heated at 60°C with an oil bath. Progress of the reaction is monitored by TLC on silica gel, using 1 1 hexane/ethyl acetate as eluant (Note 15). After about 4 hr the resulting two-phase mixture Is diluted with 20 mL of water and extracted with three 40-mL portions of ether (Note... 

Two developments in the syntheses involving addition of a Me2C group (with isopropylidenetriphenylphosphorane, Vol. 4, p. 486, Ref. 242) to fumaric acid derivatives have been published, with the idea of synthesizing chiral compounds. De Vos and Krief (whose names were originally attached to the route ) have used the dimenthyl ester 258, and obtained 74% diastereoisomeric excess (optically pure after one crystallization) of the traru-substituted cyclopropane... 

Initially applied to thermal cydoaddition of fumarates of chiral alcohols with anthracene [118] (Figure I.34.a), cooperativity was extended to other reactions of symmetrical diesters. While reactions of mixed diesters bearing a single chiral alcohol residue are poorly stereoselective, those of symmetrical diesters can be quite useful. Indeed, the formation of cyclopropane diesters 43 from succinic add diesters and BrCB Cl is poorly diastereoselective when using a mixed methyl and menthyl ester. But it becomes highly diastereoselective when performed with symmetrical dimenthyl esters (Figure I.34.b). 

Diastereoselective asymmetric induction in cobalt-catalyzed cyclopropanation is also reported for the cyclopropanations of (-)-dimenthyl and (-)-dibornyl fumarates with geminal dihalides28. 

Michael addition-condensation sequence of menthyl chloroacetate and menthyl acrylate, and cobalt(O) or nickel(0) complex-catalyzed cyclopropanation of dimenthyl fumarate with dibromomethane. The present method is characterized by good chemical and high optical yields, simple operation, preparation of both enantiomers with equal ease, and the ready availability of the starting materials. 

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