Cyclopropanes dissolving metal reduction

Dihalocydopropanes readily undergo reductive dehalogenation under a variety of conditions. Suitable choice of reagents and reaction conditions will allow the synthesis of monohalocyclopropanes or the parent cyclopropanes.19 " The ease of reduction follows the expected order I > Br > Cl > F. In general, complete reduction of dibromo and dichloro compounds is accomplished by alkali metal in alcohol,99-102 liquid ammonia103 or tetrahydrofuran (equations 28 and 29).104 The dihalocydopropanes can be reduced conveniently with LAH (equation 30).105 LAH reduction is particularly suited for difluoro compounds which are resistant to dissolving metal reductions.19 106 It is noteworthy that the sequence of dihalocar-bene addition to an alkene followed by the reduction of the dihalocyclopropyl compounds (equation 31) provides a convenient and powerful alternative to Simmons-Smith cyclopropanation, which is not always reliable. 

The transformation of 14 into 7-methoxy-fra 5-3a,9b-dimethyl-l,3,3a,4,5,9b-hexahydro-2/f-benz[e]inden-2-one (15) illustrates the use of the sequence consisting of cyclopropanation, followed by dissolving metal reduction, for the introduction of angular methyl groups into structures containing condensed alicyclic rings. 

For the synthesis of cyclopropyl amino acids, Williams has used an oxazinone auxiliary (cf. Scheme 3.12) as an electrophilic component in a sulfur ylide cyclopropanation using Johnson s sulfoximines, as illustrated in Scheme 6.41 [148]. Surprisingly, the sulfur ylide approaches from the P face the authors speculate that there may be some sort of 7t-stacking between the phenyls on the oxazinone ring and the phenyl in the sulfoximine to account for this [149]. With Corey s [147] dimethylsulfonium methylide, the diastereoselectivity was only about 75%, but with Johnson s sulfoximines (used in racemic form), only one diastereomer could be detected for most substrates studied (with the exception of R = H, [149]). Dissolving metal reduction afforded moderate yields of the cyclopropyl amino acids. 

The developments described above were predicated upon the expectation based on less highly substituted examples that the dissolving metal reduction of 35 would likewise result in regioselective rupture of the central bond of the three-membered ring conjugated to the carbonyl. No guidance was available to insure that the second cyclopropane would be insulated from electron transfer chemistry or that the a-pivaloyloxymethyl group would survive intact. Once the experiment... 

Then the carboxylic acid was converted (via the acid chloride) to the diazoketone (Chapter 9), and decomposition of the latter via the carbene and insertion produced the substituted cyclopropane. Next, the keto group was converted to a methylene unit via the Wittig, and thermolysis generated the third cyclopentyl ring. Dissolving metal reduction and epimerization in sodium ethoxide set the stage for conversion of the ester to an alkyl group. 

Facile cycloalkenylations of carbonyl groups have been carried out with cyclopropylphosphonium fluoroborates . Complex carbocyclic systems, such as the sesquiterpene a-cedrene, can be effectively constructed by cationic cyclization Epoxide cleavage which follows upon dissolving metal reduction of proximal cyclopropane rings makes possible the ready synthesis of functionalized strained ring compounds inaccessible by other methods... 

The formation of cyclopropane by reduction of 1,3-dibromopropane was discovered in 1887. Dissolving metals, in particular zinc dust in ethanol, were employed as an electron source [88], Electrochemical reduction in dimethyl-formamide at a mercury cathode has been found to give good yields of cyclopropane [89, 90], 1,3-dibromo, 1,3-diiodo and l-chloro-3-iodopropane all give greater than 90 % yield of cyclopropane, the other product being propene. 

There have been numerous reports on the reduction of activated cyclopropanes with alkali metals either dissolved in liquid ammonia or used in suspension. Most of these reactions were carried out with lithium as reducing agent. In an early study, various substituted cyclopropyl ketones were treated with lithium in liquid ammonia. rranj-l-Acetyl-2-methylcyclopropane (1, R = Me = H R = Me) gave 3,4,4-trimethyl-2-pentanone (3) as the result of... 

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