Cyclopropanone hemiacetals

Ethenylcyclopropyl tosylates 131 and 2-cyclopropylideneethyl acetates 133, readily available from the cyclopropanone hemiacetals 130, undergo the re-gioselective Pd(0)-catalyzed nucleophilic substitution via the unsymmetrical 1,1-dimethylene-jr-allyl complexes. For example, reduction with sodium formate affords a useful route from 131 to the strained methylenecyclopropane derivatives 132. The regioselective attack of the hydride is caused by the sterically... 

Due to their physiological importance, considerable efforts are currently devoted towards the total synthesis of 2,3-methanoamino acids (ACCs). The parent compound ACC 71 has been readily prepared from acrolein, through the base-induced (K2CO3) cyclization of 2-amino-4-chlorobutyronitrile [96] or from one-pot Strecker reaction of cyclopropanone hemiacetal [97]. 

Schemes. Preparation of alkyl 2-bromo-2-cyclopropylideneacetates 11 a-c by olefination of the cyclopropanone hemiacetal 9 [18 c, 19]...

Cyclopropanone hemiacetals and hydrate react with ketene to form acetoxy derivatives, e.g. 86 and 87, respectively. 5 15>80) As shown in Scheme 14, the diacetoxy compound 87 may also be obtained from the reaction of cyclopropanone with acetic acid and excess ketene. 83>... 

Table 16. Decomposition of cyclopropanones and cyclopropanone hemiacetals under acidic and neutral conditions... 

Alkyl substituted cyclopropanols and cyclopropanone hemiacetals 115,116a) aiso undergo oxidative cleavage when exposed to air or peroxides the initial products are hydroperoxides such as 148. In the case of l-methoxy-2,2-dimethylcyclopropanol, the reaction can be followed by observing the emission peaks in the NMR spectrum, and these CIDNP effects have enabled identification of radical intermediates.1154) With di-f-butylperoxylate (TBPO), the isomeric radicals 143 and 144 are formed and these may undergo a diverse number of further reactions as indicated by the complex product mixture given in Table 20. 

Another access to 1-alkoxy-l-siloxycyclopropanes 5, precursors of substituted cyclopropanone hemiacetals 6, was developed with the addition of carbenes, generated from alkylidene iodides and diethylzinc, to the trimethylsilyl enol ethers of carboxylic... 

On the other hand, the cyclopropanone hemiacetal 3 did not react with nucleophilic lithium reagents such as lithium cyanide 16), ethynyllithium 16) or aryllithium 17). 

As first reported by Wasserman, the addition of two equivalents of vinylmagnesium bromide in refluxing THF to the cyclopropanone hemiacetal 3 led to the 1-vinylcyclo-propanols 68 in 64% yields Eq. (21)10). 

In analogy to the preparation of the cyclopropanone hemiacetal 3 (vide supra, Eq. (1)7), reductive cyclization of the piperidide of 3-chloropropionic acid 193 with sodium in ether in the presence of ClSiMe3, gave the 1-piperidino-l-trimethylsilyloxy-cyclopropane 194 a which was converted to the cyclopropanol 194 b upon treatment with methanolic tetrabutylammonium fluoride. Both 194 a and 194 b can be used for the ready generation of cyclopropane derivatives thus the silyl ether 194a could be reacted directly with the vinylic Grignard reagents 195 to provide the vinyl cyclopropane derivative 196, (Eq. (61)128). 

Aside from the ready preparation of some a,p-disubstituted cyclopentanones, the utility of the cyclopropanone hemiacetal approach has been illustrated by the total synthesis of the methyl ester of 11-deoxyprostaglandin E2 342 15). Towards this end, 1-trimethylsilylbutadiynylcyclopropanol 13, readily available from the cyclopropanone hemiacetal 3 (vide supra, Sect. 2.1, Eq. (6)) was successively treated with dihydro-pyran in CH2C12 in the presence of 10% mol. equiv. of PPTS 101). Desilylation by potassium fluoride in DMF 138), formation of the lithium salt with n-BuLi and condensation with hexanal gave the propargylic alcohol 339 in 64 % overall yield. The... 

The dicyclopropyl ketimine 198 prepared from the 0,N-cyclopropanone hemiacetal 194 (vide supra, Sect. 4.9, Eq. (62)), heated in xylene with ammonium chloride for 4 hr underwent ring expansion exclusively to the enamine 399 followed by isomerization to the cyclopropyl pyrroline 400. Although further ring expansion was not observed on prolonged heating, 400 was converted to the hydrobromide 401 with anhydrous HBr 2091 which upon heating to 140 °C for 10 min experienced a second cyclopropyl imine rearrangement to provide the pyrrolizidone 403 in 51 % yield, most probably via the HBr adduct 401 by cyclization to the pyrroline 402 followed by acid-induced hydrolysis, Eq. (95) 129). 

In addition, other carboxylic acid derivatives, such as tertiary carboxamides and cyclic carbonates, readily undergo cyclopropanation reactions under similar conditions to provide cyclopropylamines ° and cyclopropanone hemiacetals," respectively. The cognate titanium-mediated coupling of imides has been shown to afford synthetically useful N-acylhemiaminals. ... 

Treatment of 3-chloropropionic esters with sodium in the presence of chlorotrimethyl-silane provides a convenient route to cyclopropanone hemiacetals. The corresponding... 

Most importantly, additions of electrophiles to vinylcyclopropanes can lead to cyclobutanones if a suitably located donor substituent is present. It was Wasserman and coworkers who showed that vinylcyclopropanols—obtained from cyclopropanone hemiacetals and vinylmagnesium bromide—can be expanded to functionalized cyclobutanones (equation 147). ... 

Cyclopropanones readily take up water, alcohols and carboxylic acids to form the corresponding hydrate, hemiketal or 1-acetoxy carbinols. The hydrates are relatively stable, but the hemiketals appear to be in equilibrium with the parent ketone, as evidenced by the fact that one hemiketal may be converted to another on standing with the appropriate alcohoF . The formation and reactions of these cyclopropanone hemiacetals is reviewed in the chapter by Salaun (cf. Chapter 13) and will not be covered extensively here. 

A similar electrochemical reduction was performed with 1,3-dibromo ketones in methanol or dimethylamine (in acetonitrile) to give cyclopropanone hemiacetals and 1-aminocyclopropan-l-ol derivatives 31. A considerable improvement in the yield was achieved when, instead of using methanol as the solvent, only a twofold excess of methanol in acetonitrile was used. The reported quantitative conversion of 2,4-dibromo-2,4-dimethylpentan-3-one to 1,2,2,3,3-pentamethylcyclopropan-l-oF in methanol could not be reproduced instead only ca. 45% yield was obtained. 

With the exception of a few cyclopropanone hemiacetals, which are readily reduced with lithium aluminum hydride in diethyl ether to give the corresponding cyclopropanols, conversion of a cyclopropyl-oxygen bond to a cyclopropyl-hydrogen bond has only been achieved by reductive dealkoxylation of 1-alkoxycyclopropylamines where the alkoxy group is either methoxy or ethoxy 3. The reductions can be carried out with various hydrides, but the optimum reaction conditions in a specific case depend on the structure of the substrate. 

When heated, cyclopropanone hemiacetals are rapidly converted into ring-opened carboxylic esters vide infra). ... 

Upon treatment with sodium methoxide ring opening of cyclopropanone hemiacetals 19 occurred to give the linear rearrangement products 20, exclusively. ... 

A variety of organometallic derivatives of cyclopropanone hemiacetals have been synthesized by the addition of the reagents RjMOMe (M = Sn, Ge, Si) across functionalized cyclo-propanones. ... 

Aliphatic hydrazines react with cyclopropanone or cyclopropanone hemiacetals, providing good access to carbinol-type adducts which are versatile sources for the synthesis of cyclo-propylidenehydrazines. Upon reacting hemiacetal 10 with A,A-dimethylhydrazine, without solvent, the distillable but sensitive hemiaminal 39 was formed in 64% yield. ... 

The bicyclic cyclopropanone hemiacetal 11 was readily reduced with lithium aluminum hydride in diethyl ether at 25 "C to give eHdo-bicyclo[4.1.0]heptan-7-ol (12). ... 

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