Cyclopropane acetal

The cyclopropane acetals [10] and [11] also hydrolyze in aqueous sulfuric acid, but the reaction mechanisms for the two are not the same. Reaction of [10] involves pre-equilibrium oxygen protonation followed by rate-determining A1 ring opening, whereas that of [11] involves carbon protonation concurrent with... 

In cases such as the one shown in equation (69), what appears to be displacement is more likely a multistep elimination-addition process.37 Carbonyl or sulfonyl groups in the 2-position greatly facilitate each of these two steps. Thus (32) on treatment with alkoxide or thiolate gave the cyclopropane acetal or thioacetal, respectively (equation 70).199 In related work, tetrachlorocyclopropene, which has interesting synthetic potential, is formed from pentachlorocyclopropane by treatment with potassium hydroxide (equation 71).200 Certain 1,1,2-trihalocyclopropanes on reaction with methyllithium in ether at low temperature afford the corresponding halocyclopropenes by 1,2-dehalogenation (equation 72).201 Similarly,... 

Scheme 5.25 Carbometallation of cyclopropane acetals reported by Nakamura et al.

The formation of nonseparable mixtures of diastereomers in the asymmetric cyclopropanation of homochiral cycloalk-2-enone 1,4-0-benzyl-L-threitol acetals with the Simmons-Smith re-agent has been circumvented by acetalizing with ( —)-(5, S)-hydrobenzoin. Treatment of (5,5)-hydrobenzoin acetals with Simmons-Smith reagent in refluxing diethyl ether provided good yields of cyclopropane acetals with a diastereoselectivity of > 13 1 (Table 2). The products were recrystallized from anhydrous diethyl ether to give diastereochemically pure products. Hydrolysis of the acetals afforded enantiomerically pure cyclopropyl ketones. Since hydrobenzoin is available in both enantiomeric forms, either enantiomer of a particular cyclopropyl ketone can be prepared via this methodology. ... 

For the synthesis of formyl-substituted cyclopropanes, acetal-substituted compounds, the functional equivalent of the formyl-substituted compounds, are employed. Either an acetal substituent is incorporated into the diazoalkane (e.g. 2,2-dimethoxy-l-diazoethane can be used ) or on the double bond. Here it provides sufficient activation for the addition step, as is seen in the synthesis of formylcyclopropane (31) and /ra .v-l,2-diformylcyclopropane (32). ... 

R)-m-[(E)-2- 7-Chloro-2-quinolyl)vinyl]-a-[o-(1-hydtoxy-1-methylethyl)phenethyl]benzyl]thio]methyl]-cyclopropane acetic acid. Montelukast. Selective leukotriene 04 receptor antagonist. Used as an antiasthmatic. Merck Co.Inc. 

Other cyclopropane derivatives in optically active form have also been prepared via a double displacement reaction of cyclic sulfate, leading to the chiral synthesis of the subunit of CC-1065 (92SL723) (Scheme 30). This cyclopropanation approach has also been utilized in the synthesis of (R)-2-methylene cyclopropane acetic acid 119 resulting from the metabolic degradation of hypoglycine A 118. 

The majority of preparative methods which have been used for obtaining cyclopropane derivatives involve carbene addition to an olefmic bond, if acetylenes are used in the reaction, cyclopropenes are obtained. Heteroatom-substituted or vinyl cydopropanes come from alkenyl bromides or enol acetates (A. de Meijere, 1979 E. J. Corey, 1975 B E. Wenkert, 1970 A). The carbenes needed for cyclopropane syntheses can be obtained in situ by a-elimination of hydrogen halides with strong bases (R. Kdstcr, 1971 E.J. Corey, 1975 B), by copper catalyzed decomposition of diazo compounds (E. Wenkert, 1970 A S.D. Burke, 1979 N.J. Turro, 1966), or by reductive elimination of iodine from gem-diiodides (J. Nishimura, 1969 D. Wen-disch, 1971 J.M. Denis, 1972 H.E. Simmons, 1973 C. Girard, 1974),... 

Cyclopropane rings are opened hydrogenolytically, e.g., over platinum on platinum dioxide (Adam s catalyst) in acetic acid at 2 - 4 bars hydrogen pressure. The bond, which is best accessible to the catalyst and most activated by conjugated substituents, is cleaved selectively (W.J. Irwin, 1968 R.L. Augustine, 1976). Synthetically this reaction is useful as a means to hydromethylate C—C double bonds via carbenoid addition (see p. 74f. Z. Majerski, 1968 C.W. Woodworth, 1968). 

Allylic acetates react with ketene silyl acetals. In this reaction, in addition to the allylated ester 468, the cyclopropane derivative 469. which is formed by the use of bidentate ligands, is obtained[303]. Formation of a cyclopropane derivative 471 has been observed by the stoichiometric reaction of the 7r-allylpal-... 

The key step in this sequence, achieved by exposure of 46 lo a mixture of sulfuric acid and acetic anhydride, involves opening of the cyclopropane ring by migration of a sigma bond from the quaternary center to one terminus of the former cyclo-l>ropane. This complex rearrangement, rather reminiscent of the i enone-phenol reaction, serves to both build the proper carbon. keleton and to provide ring C in the proper oxidation state. 

In the reaction with epoxides, y-hydroxysulfones are obtained278-280. For example, Kondo and coworkers279 synthesized various (5-lactols 226 by treating sulfone acetals 225 with terminal epoxides as shown below. Dilithiated phenylsulfonylmethylene reacted with haloepoxide and afforded 3-(phenylsulfonyl)cycloalkanols281. Treatment of y, 5-epoxysulfones 227 and 229 with n-butyllithium resulted in cyclization to form cyclopropane derivatives 228 and bicyclobutane 230, respectively282. 

Much of the early work into the rhodium(II)-catalysed formation of oxazoles from diazocarbonyl compounds was pioneered by the group of Helquist. They first reported, in 1986, the rhodium(II) acetate catalysed reaction of dimethyl diazomalonate with nitriles.<86TL5559, 93T5445, 960S(74)229> A range of nitriles was screened, including aromatic, alkyl and vinyl derivatives with unsaturated nitriles, cyclopropanation was found to be a competing reaction (Table 3). 

Cyclopropanation from the hydroxyl side of (54) should give (53). Removal of the acetal leaves ketone (55) in which the double bond has been returned to conjugation. The structure remaining is very like ketone (56), the classical product of a Robinson annelation (pT175). Analysls... 

Treatment of aromatic aldehydes such as p-anisaldehyde with Zn-powder and l,2-bis(chlorodimethylsilyl)ethane 45 give Zn-carbene adducts such as 2096 which add readily to olefins such as cyclohexene [22, 26] or styrene [26] to give high yields of cyclopropanes such as 2097 and the oxide 47 [26]. Acetals such as 2098 react analogously with cyclohexene to afford the endo and exo cyclopropanes 2099 and 2100 [22, 27] (Scheme 13.11). 

Cyclopropyl sulfones were shown to be obtained either by cyclization of y-p-tosyloxy sulfones 232 with base or by treatment of phenylsulfonylacetonitrile 233a or ethyl phenyl sulfonyl acetate 233b with 1,2-dibromoethane in the presence of benzyltriethyl-ammonium chloride (BTEA) and alkali in good yields. Chang and Pinnick synthesized various cyclopropane derivatives 234 upon initial treatment of carbanions derived from cyclopropyl phenyl sulfone with either alkylating agents or a carbonyl compound and subsequent desulfonylation, as shown below. 

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