From Cyclopropanone Hemiacetal

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). 

Since the hemiacetal 3, can now readily be prepared from cheap commercially available starting materials (vide supra, Eq. (1))7), this reaction constitutes a convenient source of 1-vinylcyclopropanols. Otherwise, the 1-ethynyl-cyclopropanols 9, also easily available from 3 or from its magnesium salt 10 (vide supra, Eq. (4) and (6) underwent either lithium aluminium hydride reduction in refluxing THF to lead exclusively to the E-1-vinylcyclopropanols 69 or reduction with dicyclopentadienyl-titanium hydride in ether at 0.°C, prepared from isobutylmagnesium halides and a catalytic amount of dicyclopentadienyl titanium dichloride (r -CjH TiCk), to yield exclusively the Z isomer 70, Eq. (22) 15,39). 

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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). ... 

Scheme 22 One-pot Diels-Alder reaction of tetrasubstituted thiophene 1 -oxides and cyclopropyl-alkenes derived from cyclopropanone hemiacetal [14]...

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]. 

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>... 

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... 

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). 

Excellent yields of j5-hydroperoxy esters, e.g. 41, were obtained from the autoxidation of phenyl-cyclopropanone hemiacetals in benzene. 

Cyclopropanone hemiacetals. A convenient preparation of these compounds involves the reductive coupling of 1-alkenes with ethylene carbonate. The catalyst is derived from a combination of RMgCl and (( -PrO),TiCl. 

Cyclopropanone hemiacetals from ketenes and diazo compds. 

A number of 1-substituted cyclopropanols are now available by nucleophilic attack on cyclopropanone, which may be generated in situ from its hemiacetals or other stable precursors. Although the cyclopropanols are obtained in these reactions without ring cleavage, nucleophilk decomposition of JV-alkyl-cyclopropanimine (274) gives a regiospecific C-1—C-3 cleavage (Scheme 41). ... 

A significant step in studying the chemistry of cyclopropanones has resulted from the discovery that many labile carbonyl derivatives such as hemiacetals and carbinol amines are useful precursors of the parent ketone. 4-6> Such derivatives may be isolated, purified and used as cyclopropanone substitutes or, alternatively, may be generated in solution and used as in situ precursors. As a result of these advances, exploration of cyclopropanone chemistry has recently been accelerated. The aim of this article is to review some of this chemistry, noting areas where there may be potential applications in synthesis. 

The preparation of cyclopropanones by photochemical decarbonylation 8-i°) js illustrated by the formation of 1-ethoxycyclopropanol from the photolysis of tetramethylcyclobutane-l,3-dione (17) in ethanol.9 a> As shown in Scheme 4, the desired hemiacetal is accompanied by a number of side products including ethyl isobutyrate which results from the... 

Cyclopropanone ethyl hemiacetal was first synthesized by the reaction of ketene and diazomethane 1n ether at -78°C in the presence of ethanol.4 The yield is low (43%) and the reaction 1s hazardous, especially when a large-scale reaction is required. The method described in this procedure for the preparation of cyclopropanone ethyl hemiacetal from ethyl 3-chloropropanoate... 

CYCLOPROPANONE ETHYL HEMIACETAL FROM ETHYL 3-CHLOROPROPANOATE... 

Electrochemical reduction of aa -dibromo-ketones has been studied as a potential route to cyclopropanones no such species was detected, the products obtained being rationalized in terms of the intermediacy of an oxyallyl zwitterion or an enol allylic bromide. Later, however, cyclopropa-none hemiacetals were isolated from such reductions in methanol. 

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