Cyclopropyl compounds

Banwell, M.G. (1996) Cyclopropyl Compounds as Chemical Building Blocks Total Syntheses of the Alkaloids (—)-Colchicine, Imerubrine and Grandirubrine. Pure and Applied Chemistry, 68,... 

Cyclopropanation of the 4,6-diene function proceeds selectively at the 5,6-double bond. Thus, reaction of 185 with the ylide from trimethyl sulfonium iodide and sodium hydride, in DMSO, affords predominantly the a-cyclopropyl compound (187) accompanied... 

The opening of cyclopropylcarbinols to homoallylic bromides constituted the first use of cyclopropyl compounds for the stereocontrolled synthesis of natural products. The cyclopropyl conjunctive reagents enhance the richness of this notion. The stereocontrolled opening of vinylcyclopropanes by a homopentadienyl proton shift provides an approach to trisubstituted olefins and thereby a new strategy. The fungal prohormone methyl trisporate B (224) as summarized in Scheme 15 illustrates this conceptual development97). 

Several diverse classes of potent CCR5 antagonists, Figure 7 have recently been reported [2], Scaffolds reported to support high potency against CCR5 in antiviral cellular assays included the aminocyclohexyl (compound 13) [45], 4,4-disubstituted piperidine (compound 14, GSK163929) [46,47], tetrahydro-2/T-1,3-oxazine (compound 15) [48], pyrrolidine (compound 16) [49], cyclopropyl (compound 17) [50] and 2,3-dihydro-lH-indene (compound 18) [51]. 

Thus, allyl telluronium ylides generated in situ from the corresponding telluronium salts in the presence of Li salts react with a,)3-unsaturated esters and amides to afford trans-2-vinyl-/rany-3-substituted cyclopropyl compounds in high yieds. 

Twenty-four cyclopropyl compounds were screened for their antiproliferative activities, eighteen were found to be active and five appeared to be promising pure antiestrogens, superior to tamoxifen 128 not only in the treatment of the estrogen-dependent tamoxifen-responsive breast cancer patients, but also in the treatment of the estrogen-independent, tamoxifen non-responsive, breast cancer patients. 

The studies were conducted in the absence or presence of exogenous estradiol to reveal the estrogen-dependent nature of the cyclopropyl compounds [179,181]. 

Diazothioxanthene is the usual precursor for the thioxanthylidene carbene, which can be shown to have a nucleophilic character. It adds to fumaric or maleic esters to form cyclopropyl compounds, but does not react with cyclohexene (78JOC3303). Reaction with alkyl phosphites is a very useful means of preparing the phosphonate derivatives (72JIC985). 

Cremer and coworkers investigated a number of potentially homoconjugated cyclopropyl compounds such as the monohomotropylium cation203- 205, the 1,4- and 1,3-bishomotropylium cation208, the trishomotropylium cation209, the barbaralyl cation210 and the cyclobutenyl cation211. All these cations have the choice between a closed cyclopropyl structure (la), an open cyclopolyenyl structure (Ic) and an intermediate structure (lb) as demonstrated in the case of the monohomotropylium cation. 

For all cations considered, 13C NMR spectra have been measured in solution while direct structural information on the question as to whether structure Ia, lb or Ic corresponds to a minimum energy form was completely missing. Therefore, the structural problem was solved by utilizing the ab mirio/IGLO/NMR method. Since results of this work will be reviewed in another chapter of this volume (see Chapter 7), we refrain from discussing calculated NMR data for potentially homoconjugated cyclopropyl compounds at this point. 

TABLE 1. Internuclear distances (A) of some cyclopropyl compounds and cations... 

There is limited experimental magnetic information on norcaradienes and most of the currently available information comes from theory. Pikulik and Childs examined the H NMR spectra of the type 110 and pointed out that the chemical shifts of the C(7) and C(l)/C(6) proton resonances were anomalous as compared to complexes of related cyclopropyl compounds such as 111 and 112246. They argued that the chemical shifts of 110 could be accounted for on the basis of an induced ring current. 

A wide variety of organometallic methods of carbon-metal tr-bond formation3 have been employed in the synthesis of cyclopropyl-metal compounds. Consequently, with few exceptions the preparation of almost any main group or transition metal cyclopropyl compound has precedence in the literature. In this section only an overview, rather than a comprehensive survey, of the essential synthetic methods of cyclopropyl-metal com-... 

The synthesis of cyclopropyl compounds containing the olefin replacement for the amide bond but without the additional primary chiral amino substituent were prepared by modified Julia olefination procedures. Addition of the benzothiazole sulfone 44 to aldehyde 39 gave trityl protected olefins in a 1 1 ratio. These... 

Cleavage of the optically active cyclopropyl compounds (I M = Li)5 by methanol in ether or ether/1,2-dimethoxyethane and (I M = SnMe3)6 by concentrated hydrochloric acid in carbon tetrachloride and by anhydrous hydrogen bromide in CC14 also take place with retention of optical activity and configuration, viz. 

In an effort to explain these atypical reactivity patterns, a mechanistic postulate based on direct electrostatic activation (DEA) was proposed (Scheme 3.8). Indeed, the zwitterionic iminium ions derived from catalyst 10 and a,/i-un saturated aldehydes enable both iminium geometry control and direct electrostatic activation of the approaching sulfonium ylides. The combination of geometric and electronic control seems to be essential for enantio- and diastereocontrol in the formation of the desired cyclopropyl compound. 

An unusual methylene-transfer reaction along with [4-I-4] cyclodimerization was observed, when 5,A-d5-tert-butylthiophene 1-oxide was refluxed in toluene with 2-methylene-l,3-dimethylimidazolidine <2001GL758>. Initially a Michael adduct is formed by the addition of 104 to 103. This adduct upon intramolecular cyclization gives the cyclopropyl compound with elimination of a carbene. This on further oxygen-transfer reaction gives products 105 and 106. The 1,4-Michael adduct on further Michael reaction with 103 produces another adduct, which on cyclization followed by elimination of 104 gives 107 (Scheme 25). 

Rhodium compounds and complexes are also commercially important catalysts. The hydroformylation of propene to butanal (a precursor of hfr(2-ethyUiexyl) phthalate, the PVC plasticizer) is catalyzed by hydridocarbonylrhodium(I) complexes. Iodo(carbonyl)rhodium(I) species catalyze the production of acetic acid from methanol. In the flne chemical industry, rhodium complexes with chiral ligands catalyze the production of L-DOPA, used in the treatment of Parkinson s disease. Rhodium(II) carboxylates are increasingly important as catalysts in the synthesis of cyclopropyl compounds from diazo compounds. Many of the products are used as synthetic, pyrethroid insecticides. Hexacyanorhodate(III) salts are used to dope silver halides in photographic emulsions to reduce grain size and improve gradation. 

In the case of a three-membered ring attached spiro-fashion to a six-membered ring, a comparison of the series 28—31 in Table 9 shows that the barrier is reduced in the cyclopropyl compounds. 93,95,96)... 

Methylene transfer. Treatment of the sulfonium salt (1) with potassium r-butoxide in 1,2-dimethoxyethanc results in internal methylene transfer to give the cyclopropyl compound (2) in... 

Although reaction of a,/3-unsaturated carbonyl compounds with diazo compounds generally gives cyclopropyl compounds in low yields, in the presence of SbFs, the cyclopropanation of a,)8-unsaturated carbonyl compounds with diazocarbonyl compounds proceeds very well to produce the desired products in good yields (Eq. 22) [41]. 

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