Cyclopropanes from diols

Considering the industrial importance of cyclopropanes in the pesticide field, it is not surprising that chiral ferrocenylphosphines have been applied as control ligands for the palladium-catalyzed enantioselective formation of cyclopropanes from the dicarbonate of 2-butene-1,4-diol and malonates, leading to 70% ee (Fig. 4-32e) [179]. Ferrocenylphosphines also induce chirality in the reaction of sulfonyl-substituted propenyl carbonates and acrylic esters to methylenecyclopentanes (up to 78% ee (Fig. 4-321)) [180], with potential applications in natural product synthesis. These examples show that the synthetic potential of chiral ferrocene derivatives is not yet fully exploited, and one may look forward to new applications. 

Gassman et al have published full details of their work on the synthesis of fused cyclopropanes by reaction of l-chloro-2-alkylcycloalkenes with organo-lithium reagents (see Vol. 4, p. 244), and further aspects of the synthesis of cyclopropanes from 1,3-diols using McMurry s reagent have been reported. ... 

Treatment of diethyl malonate and related compounds with 1,2-dihaloethane in the presence of base constitutes a classical method of cyclopropane synthesis296"300. The reaction can be conveniently carried out under PTC conditions. An improved method utilizing solid-liquid phase transfer catalysis has been reported298. The reaction of dimethyl or diethyl malonate with 1,2-dibromoalkanes except for 1,2-dibromethane tends to give only low yields of 2-alkylcyclopropane-l, 1-dicarboxylic esters. By the use of di-tm-butyl malonate, their preparations in satisfactory yields are realized (equation 134)297. The 2-alkylcyclopropane derivatives are also obtained from the reaction of dimethyl malonate and cyclic sulfates derived from alkane-1,2-diols (equation 135)301. Asymmetric synthesis... 

An auxiliary-directed asymmetric Simmons-Smith reaction was used by a Hoff-mann-La Roche group88 for the synthesis of an ethynyl cyclopropane that served as the A-ring precursor to Vitamin D derivatives [Scheme 2.41]. High diastereoselectivity was achieved with the aid of the dioxolane ring prepared from (/ft/f)-(-)-butane-2,3-diol. The acid conditions for hydrolysis of the dioxolane ring were mild enough to leave the cyclopropane ring unperturbed. Dia-stereoselective cyclopropanation of acetals derived from 1,2-di-O-benzyl-L-threi-tol have also been reported 90... 

Reductive dehalogenation is an efficient method of synthesis of cyclopropanes spiroannulated to five- and higher-membered carbocycles (i.e. compounds in which spiroannulation does not result in accumulation of extra strain) . The required gem-(dihalomethyl)cycloalkanes are usually prepared by halogenation of the precursor diols (equation 1). The cyclization is most efficiently accomplished in the Zn-alcohol-water system . For example, spiro[2.5]octane 7 was prepared in 91% yield using this procedure. This method is useful even for a one-step preparation of bis-spirocyclopropyl compounds as exemplified in equation 2. However, the application of the reductive dehalogenation method to the synthesis of more strained SPC (i.e. spirohexane or spiropentane) often leads to rearranged products. For example, methylenecyclopentane was the only product obtained from bis(bromomethyl)cyclobutane (equation 3) ... 

Next, the most efficient route to (+)-7b (MGS0028), to date, via monoprotected fluo-rinated diol 43 and ketal 45 as key intermediates is discussed (see Schemes 3.6 and 3.7) [45]. Key intermediate 43 was synthesized from hydroxycyclopentenylacetate 39 in four steps (i) fluorination of the dianion of 39 (85% yield) to form 40, (ii) vanadium-mediated epoxidation of 40 to give epoxide 41 (93% yield), (iii) protection of the hydroxyl moiety of 41 to form TBS-ether 42 (95% yield), and (iv) cyclopropanation of 42 through ringopening of the epoxide moiety to afford key intermediate 43 (96% yield). It should be noted that the epoxidation of 40 proceeded with excellent stereoselectivity to give the... 

The unusual cyclopropane 551 was isolated [probably as the (5)-isomer] from Pistacia vera, together with the hydrated analog 552 551 was synthesized by Grignard reaction of cyclopropylmagnesium bromide with 4-methyl-3-cyclohexenone, and the diol 552 by lithium aluminum reduction of the epoxide of 551. ... 

The most popular lands of the diols for asymmetric synthesis are bis-secondary diols that have a C2 axis of symmetry [212]. The presence of the symmetry axis avoids the formation of diastereoisomeric esters or acetals [213], (1R, 27 )-Cyclohexanediol 1.34 (n = 1) has been used as an auxiliary in asymmetric cyclopropanation [214] and (IS, 2S)-cycloheptanediol 1.34 (n = 2) in 1,4-addition of cuprates[157], Dioxolane derivatives of 1.34 have been used for asymmetric P-ketoester alkylations [215] and cuprate 1,4-additions [216]. Linear 1,2-diols 1.35 (R = Me, i-Pr, c-CgH j, Ph) and functionalized 1,2-diols 1.36 (Y = COOalkyl, CONR 2, CH2OR ) are readily available from optically active tartaric acids 1.36 (Y = COOH). Acetals derived from these diols are valuable reagents m asymmetric synthesis [173, 213, 217], as the related 1,3-diols 1.37. Acetals of 1,3-butanediol 137 (R = Me, R = H) have also been used. When these acetals are formed from aldehydes under thermodynamic conditions, one 1,3-di-oxane stereoisomer often predominates. In this favored isomer, the substituent from the aldehyde and the methyl group from 1.37 are both in equatorial orientar... 

Scheme 7 Ozonization of alcohol (79) followed by treatment of the ozonide with Me2S afforded hydroxy ketones (80), whose acetate derivatives was converted to indenone (83). Hydroxy ketone (84), prepared from (83) was converted to compound (85), whose acetate on oxidation gave diol (87). Its transformation to butenolide (88) was easily carried out. This on oxidation and reduction produced hydroxy phytuberin lactone (89), which was converted to its sulfonyl derivative. Reductive removal of the sulfonate group yielded the cyclopropane derivative (91), which on subjection to reductive cleavage with lithium in liq. NH3 yielded phyberin lactone (92) and deacetyl phytuberin lactone (93)...

Sharpless and Kim reported a one-pot synthesis of cyclic sulfates 96 from 1,2-diols via catalytic oxidation with ruthenium chloride51. The cyclic sulfates 96 thus formed on treatment with nucleophiles give /2-sulfates 97, which in turn are hydrolyzed to the / -hydroxy compounds 98 (equation 54). Hence the cyclic sulfates 96 are synthetically equivalent to epoxides. The results of ring opening of cyclic sulfates 96 are shown in Table 4. When the reaction of 99 with malonate anion is carried out in DME, the /2-sulfate moiety serves as a leaving group to give cyclopropane 100 (equation 55)51. 

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