Cyclopropyl halide reduction

The key cyclization in Step B-2 was followed by a sequence of steps that effected a ring expansion via a carbene addition and cyclopropyl halide solvolysis. The products of Steps E and F are interesting in that the tricyclic structures are largely converted to tetracyclic derivatives by intramolecular aldol reactions. The extraneous bond was broken in Step G. First a diol was formed by NaBH4 reduction and this was converted via the lithium alkoxide to a monomesylate. The resulting (3-hydroxy mesylate is capable of a concerted fragmentation, which occurred on treatment with potassium f-butoxide. 

Several studies of the electrochemical reduction of cyclopropyl halides have been reported in the literature 20,26,27,55) t it appears that reduction occurs without complete loss of stereochemical integrity. The predominent stereochemical pattern involves reduction with overall (partial) retention of configuration. The following examples are representative ... 

The partial loss of configuration often observed during reduction of cyclopropyl halides may actually occur via the corresponding cyclopropyl radicals, which lose configuration rapidly °>. In that event, their behavior would resemble that of vinyl halides, as exemplified by the 3-iodo-3-hexenes 16>. Occasional cases of partial inversion could be associated with shielding of the cyclopropyl carbanion by the electrode surface, with concomitant protonation on the other face of the carbanion S8>. 

As was indicated previously, several other parameters can affect the stereochemistry of reduction of cyclopropyl halides 20>. For example the optical purity of 59 produced from the electrochemical reduction of 58 in acetonitrile... 

Reduction of chiral cyclopropyl halides using Sml2 has been investigated... 

A classical method using Na- or Li-liquid ammonia (Birch reduction conditions) is effective for reductive dehalogenations of aryl and vinylic halides, but it is not always successfully applied to alkyl halides, although cyclopropyl halides and bridgehead halogens are exceptions.Under such conditions, the reactions are often accompanied by side reactions, such as elimination, the Wurtz coupling reaction, cyclization and reduction of carbonyl compounds. An example, a synthesis of pentaprismane (1), is shown in Scheme 4. ... 

The reduction of tertiary cyclopropyl halides with alkali metal naphthalenides leads to a similar situation. After treatment of a 78 22 and a 25 75 mixture, respectively, of r-1-bromo-l-methyl-c-2-methyl-r-2-phenylcyclopropane (110) and its isomer (111) with LiN in THE at 20°C, protonation with methanol led to identical 45 55 mixtures of r-l-phenyl-l,c-2-dimethyl- and r-1-phenyl-l,r-2-dimethylcyclopropanes (112 and 113). 

SCHEME 13. Alkali metal naphthalenide reductions of cyclopropyl halides... 

SCHEME 15. Alternative pathway for the alkali metal naphthalenide reduction of the cyclopropyl halides 50-52 and 118-HaE ... 

The electrochemical reduction of cyclopropyl halides has been widely investigated mainly in relation to its stereochemistry. No ring-opened products have been reported yet but substitution of the halogen by a hydrogen usually proceeds in high yields. Both monohalocyclopropanes, mostly bromide derivatives, and gem-dihalocyclopropanes were investigated. Several groups have studied the stereochemistry of the electroreduction... 

TABLE 5. Electrochemical stereospecificity in the cathodic reduction of optically active cyclopropyl halides... 

Scheme 4.17 Reduction of cyclopropyl halides with calcium reagents in different forms...

Since il does not. olhei possible reactions of RX7 must be considered. In some reductive cleav ages ol some substituted cyclopropyl halides, an electron transfer to RX- appears to be required, leading to a dianionic fragmentation transition stale (composition RX-. w-ith associated counterions)... 

Elimination reactions of cyclopropyl halides can provide a simple route to cyclopropenes, since the former are readily available by semi-reduction of the dihalogeno-carbene adducts of olefins. An example is shown in Scheme 15. ... 

A review of the stereochemical consequences of electrochemical reduction including dehalogenation of cyclopropyl halides has been published. " Polaro-graphic reduction proved to be the most convenient method of introducing hydrogen (or its isotopes) into (305). ... 

It was reported last year that the stereospecificity of tri(n-butyl)tin hydride reduction of cyclopropyl halides is dependent upon the other substituent present at the reaction site, i.e. the ability of the substituent to stabilize the radical or affect its geometry. Norcarane derivatives (618) have been made by standard methods and reduced with HSnBu3 under a variety of experimental... 

The former reduction is thought to occur by two single electron transfers (SET) from the metal surface to the cyclopropane derivative providing a halide and cyclopropyl anion initially. The latter is protonated by the solvent thus leading to the monohalogen derivative which can undergo the reduction process for a second time. 

The bromide was prepared from the cyclopropyl earblnol obtained by reduction and fxotu the halide a Grignard compound was formed. This/compound treated with formaldehyds gave among other products cydobutylcarblspl.8 Whether this is to be attributed to isomerization or to the presence of cyclobutanol in the cycloprop>l alcohol is uncertain. 

Tandem cyclization was not obtained for 88. However, this could be achieved for 89 in which the vinyl halide was further activated with an acetyl group [Eq. (54)] and the catalyst was used in a larger amount (0.3-0.5 eq.) [238]. In explanation of the difference, it was proposed that the subsequent formation of the cyclopropyl ring by 3-. vu-cyclization is reversible. The electron withdrawing group at the final radical center promotes its rapid reduction [by the excess Ni(I) complex] to a carbanion that is quickly protonated [238]. 

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