Dibromocyclopropanation reaction

The reaction of 1-ethoxycyclohexene with dibromocarbene gives less stable products which are difficult to process. The dibromocyclopropane (39)... 

Reaction of dibromocyclopropane (39) with hot quinoline gives 1-ethoxy-cyclohepta-l,3,5-triene (37) in 32% yield. Dihalocyclopropanes prepai ed from larger ring enol ethers do not react with hot pyridine but afford products with hot quinoline formed by transannular reactions. 

An important synthetic application of this reaction is in dehalogenation of dichloro- and dibromocyclopropanes. The dihalocyclopropanes are accessible via carbene addition reactions (see Section 10.2.3). Reductive dehalogenation can also be used to introduce deuterium at a specific site. The mechanism of the reaction involves electron transfer to form a radical anion, which then fragments with loss of a halide ion. The resulting radical is reduced to a carbanion by a second electron transfer and subsequently protonated. 

An Arbuzov reaction between gem-dibromocyclopropanes yields phosphonate esters (55) accompanied by debrominated compounds successful reaction requires the presence of traces of water (and is thus not the normal Arbuzov reaction) which, by studies with D2O, has been shown to supply the a-proton of (56), Normal Arbuzov reactions, using ethyl diphenyl phosphite, have been used to prepare a phosphonate isostere of B-D-arabinose-1,5-diphosphate. ... 

It is supposed that the nickel enolate intermediate 157 reacts with electrophiles rather than with protons. The successful use of trimethylsilyl-sub-stituted amines (Scheme 57) permits a new carbon-carbon bond to be formed between 157 and electrophiles such as benzaldehyde and ethyl acrylate. The adduct 158 is obtained stereoselectively only by mixing nickel tetracarbonyl, the gem-dibromocyclopropane 150, dimethyl (trimethylsilyl) amine, and an electrophile [82]. gem-Functionalization on a cyclopropane ring carbon atom is attained in this four-component coupling reaction. Phenyl trimethyl silylsulfide serves as an excellent nucleophile to yield the thiol ester, which is in sharp contrast to the formation of a complicated product mixture starting from thiols instead of the silylsulfide [81]. (Scheme 58)... 

The carbonylation reaction of the gem-dibromocyclopropanes 159 bearing the chloromethyl group leads via ring-opening to the 7, d-unsaturated carboxylic... 

The presence of trialkyl phosphite 198 in the above mentioned reduction of the gem-dibromocyclopropanes 150 with dialkyl phosphonate and triethylamine alters the reaction course. Dialkyl cyclopropanephosphonates 199 are produced via reductive phosphonation [104]. Trialkyl phosphite participates in the carbon-phosphorous bond formation. It is supported by the exclusive formation of diisopropyl cyclopropylphosphonate in the phosphonation reaction with diethyl phosphonate and triisopropyl phosphite. (Scheme 74)... 

The discovery of carbene and carbenoid additions to olefins was the major breakthrough that initiated the tapping of this structural resource for synthetic purposes. Even so, designed applications of cyclopropane chemistry in total syntheses remain limited. Most revolve around electrophilic type reactions such as acid induced ring opening or solvolysis of cyclopropyl carbinyl alcohol derivatives. One notable application apart from these electrophilic reactions is the excellent synthesis of allenes from dibromocyclopropanes 2). 

Conjugated ketones and esters generally react with chloroform under basic conditions by Michael-type addition of the trichloromethyl anion to the C=C bond or by insertion of dichlorocarbene into the C=C bond, depending on the substitution pattern of the conjugated system (see Sections 6.4 and 7.3). The corresponding reaction with bromoform under basic conditions produces 1,1-dibromocyclopropanes. 

As dibromocyclopropanes can easily be synthesized by reacting a cycloalkene with bromoform in the presence of a base [16], this method affords an alternative procedure for cyclopentenone annelation onto cyclic alkenes. It should be noted that in the Pauson-Khand reaction, which is probably the most direct cyclopentenone annelation reaction, the reaction using cyclohexene gives the product only in very low yield [11,17]. Also, the position of the original alkynyl substituent on the product double bond is opposite to that in the present reaction. Thus the two reactions are complementary. 

For reviews on the transformation of dibromocyclopropanes to allenes (see so-called Doering-Skattebol-Moore reaction) see (a) Hopf H (1980) In Patai S (ed) The Chemistry of Ketenes, Allenes and Related Compoimds Wiley, New York, Part 2, Chapter 2, p 779 ... 

The preparation and dehalogenation of gem-dibromocyclopropanes to give allenes can be carried out in one step by the reaction an excess of olefins with... 

Following the report on reactions of 1,1-dibromoalkenes 9 with triorganozincates, the same group reported reactions of 1,1-dibromocyclopropanes 14 (equation if. 

Treatment of gem-dibromocyclopropane 34 with Bu3ZnLi from —85 to 0°C generates 1-butylcyclopropylzinc 36 via the 1,2-migration of the zincate carbenoid 35 (equation 27)24. Subsequent Pd°-catalyzed cross-coupling reactions afford cyclopropane... 

Formally, in the two steps of the DMS-process (dibromocyclopropanation and reaction with alkyllithium) a carbon atom is inserted between the two centers of a double bond. The reaction may be extended to the preparation of still higher cumulated bond systems as well as to numerous other — including functionalized — allenic systems which cannot or only with much effort be prepared by other routes. The examples shown here serve illustrative purposes only, for more extensive coverage of the literature the reader is referred to the various reviews and monographs which have appeared recently [66, 69, 71, 72]. 

No other dibromocarbene adduct has probably been used in more subsequent reactions than that of benzvalene. Besides the allene producing reaction shown, Christl and his students have described dozens of transformations of this versatile gem-dibromocyclopropane, among them practically all reaction-types discussed in the different chapters of this review [92],... 

Scheme 2. Proposed reaction pathways in the indirect electrochemical reduction of geminal dibromocyclopropanes by chromium (II)...

Cyclic allenes have been obtained in high yields, as illustrated by the synthesis of 1,2-cyclononadiene from the dibromocarbene adduct of the readily available cyclooctene (equation 51).138 The smallest stable cyclic allene known to date is (14) it was prepared from the dibromocyclopropane (13) in high yield.139 A small amount of the tricyclic compound (15) was also obtained (equation 52). The cyclic allene (14) did not undergo dimerization even on prolonged standing at ambient temperatures. In contrast, the unsubstituted analog was detected only at -60 °C by H NMR. It should also be noted that cyclohexa-1,2-diene was generated by the reaction of methyllithium on dibromobicyclo[3.1.0]hexane and trapped as the Diels-Alder adduct.160... 

When the carbene or carbenoid resulting from a dihalocyclopropane is unable to rearrange to the al-lene due to steric or other factors, insertion or addition reactions characteristic of carbenes take place. Thus dibromonorcarane on reaction with methyllithium gives a bicyclobutane derivative by insertion of the carbene into a 0-C—H bond (equation 57).178 Allene formation is sterically unfavorable in this case. Similarly, dibromotetramethylcyclopropane gives l,2,2-trimethylbicyclo[1.1.0]butane instead of tetra-methylallene (equation 58).179 181 An example involving a tricyclic dibromocyclopropane is given in equation (59).182... 

In the same publication, an enantioselective process was attempted wherein commercially available (2f ,3/ )-butane-2,3-diol was used to generate the chiral cyclopentene 57, which was cyclopropanated to afford gcm-dibromocyclopropane 58 (Scheme 4.20). Unfortunately, when this substrate was subjected to the reaction conditions outlined above, product 59 was obtained as a 1 1 mixture of diastereomers. This result implies that selectivity in these trapping processes is unaffected by the presence of a chiral auxiliary on the remote carbon of the cyclopentane framework. 

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