Protonated cyclopropane from esters

The acid-induced reaction of aryldiazomethanes with olefins gives arylcyclo-propanes in addition to olefins and esters. The cyclopropanes are formed stereo-specifically and their yields are largest in reactions with olefins which on cation addition give secondary carbonium ion centres. The use of deuteriated acids leads to partial incorporation of deuterium in the cyclopropane adducts, whereas the use of [a- H]-phenyldiazomethane leads to partial loss of deuterium, suggesting a slow proton transfer from the acid to the diazo-compound a carbenoid rather than a free carbene appears to be involved. 

The cyclopropane cyclizations by elimination of triflinic acid (CF3S02H) are readily effected by basic treatment of triflones (trifluoromethyl alkyl sulfones) with activated /-protons (equations 46 and 47)39. The cyclopropane diesters 45 are formed on treatment of 44 with potassium hydride in DMSO or sodium methoxide in methanol (equation 48). In contrast, the monoester 46 failed to give the desired cyclopropane40. Addition of carbanions derived from /f, y-unsaturated phenyl sulfones to a, /i-unsaturated carboxylic esters and subsequent elimination of benzenesulfinate ion give cyclopropanes possessing the unsaturated side chain and the ester function in trans positions (equation 49)41. 

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)... 

A ketone, resulting from the normal oxidation of a secondary alcohol, is obtained along with an alkene, resulting from an opening of the cyclopropane. The secondary product can be explained by the intermediacy of either a chromate ester, or a protonated alcohol. Treatment of the starting alcohol with 10% HC1 leads to a 87% yield of the secondary product, suggesting a mechanism involving PCC as a proton donor. 

As an alternative to a radical chain mechanism for this bromination, a cationic mechanism has been proposed for the reaction between 48 and A-bromosuccinimide. It involves attack of bromine at C6 of 48 leading ultimately to the cyclopropylmethyl cation A. This cation is a bromo derivative of tricyclic cyclopropylmethyl cation, which has been shown to be the common intermediate in the solvolysis of esters of tricyclo[3.2.1.0 ]octan-3-ol, endo- and exo-tricyclo[3.2.1.0 ]octan-4-ol and of cxo-bicyclo[3.2.1]oct-2-en-7-ol. It has been shown that under long-lived ion conditions at — 78 C such cations are the most stable species that are formed from bicyclo[3.2.1]oct-2-en-3-ol and from bicyclo[3.2.1]octa-2,6-dienes. In kinetically controlled reactions, which are postulated to proceed via cyclopropylmethyl cations a tendency can be seen towards formation of products retaining the cyclopropane ring. This case is achieved through loss of one of the protons at C4 of A. 

A large number of cyclopropanes have been synthesized from cyclopropyl sulfones, cyclopropyl sulfoxides and cyclopropyl sulfides by taking advantage of the acidity of the cyclopropyl proton a to the C-S bond. Butyllithium is used almost exclusively as the base. The cyclopropyl anions obtained are capable of reacting with alkyl halides, aldehydes, enamines, epoxides, esters. 

The electrophilic bromine cation can also be generated from A -bromosuccinimide (NBS). When 2-methylene-6,6-dimethylbicyclo[3.1.0]hexane with an ester function at the bridgehead position was treated with NBS in diethyl ether the electrophilic attack took place at the terminal position of the C—C double bond and the cyclopropane ring was opened to give a cyclopentene derivative. Due to the lack of a reactive nucleophile, a proton was eliminated. The reduction of the ester function did not change the course of this reaction. With tert-hvAy hypochlorite, the corresponding chloro product was obtained. ... 

The most significant advance in the synthesis of cyclopropanes during the course of this Report has come from the work of Olofson and co-workers. By employing the arpoon base, lithium 2,2,6,6-tetramethylpiperidide (LiTMP) the stringent selectivity requirements for proton abstraction in chloromethyl esters and ethers are... 

A project directed towards the synthesis of chrysanthemic acid enantiomers illustrates some of our recent work on cyclopropano-pyranosides. The sequence (Scheme 40) that had worked so well (25) for the preparation of the simple cyclopropyl ketone (169) from the methanol adduct (168) was not adaptable for preparation of the gem-dimethyl analogue (171). The photoaddition of isopropanol to (83) gave an excellent yield of (170), but efforts to convert this into (171) were not encouraging. However, the Wittig cyclopropanation (24) of epoxide (51) gave the ester (172) whose stereochemistry was deduced by two pieces of nmr data (a) the value J12 < 1 Hz (76) (see Scheme 4), and (b) a ten percent Nuclear Overhauser Effect between H-1 and the methyl protons. 

Hantzsch esters (e.g. 2,6-dimethyl-l,4-dihydropyridine-3,5-dicarboxyUc acid diethyl ester), analogues of NAD(P)H, transfer hydride from the 1- and 4-positions, the question of which occurs first may be resolved by the use of a probe such as (Z)-ethyl Q -cyano-jS-bromomethylcinnamate, which will only accept one hydride since it rapidly cyclizes after the first addition to give a cyclopropane derivative. The use of 1- and 4-deuterium-labelled Hantzsch esters indicated that it is the 4-proton that is transferred first. ... 

Gassman and Creary have reported that the centra bond of succinic esters can be cleaved with sodium in liquid ammonia. This method gives dimethyl glutarate from dimethyl cis- and trans-cyclopropane-l,2-dicarboxylates. The C-1—C-2 cleavage of a 1,2-diphenylcycIopropane which is part of a more complex, tricyclic compound has been effected by lithium in ammonia. Although it is known that lithium-ammonia reduction of a cyclopropyl ketone cleaves the bond which will allow tlw best overlap with the carbonyl Tt-system, the steric course of protonation at the f(-carbon has not, until recently, been known. Reduction of (301) at — 78 °C gives (302X the product with inversion, and (303),... 

Czochralska [113] investigated the reduction of the optically active 2-phenyl-2-chloropropionic acid at a mercury cathode in acidic ethanolic solution. It was found that inversion took place during electrolytic reduction, and the yield of optically active product amounted to 77.2-92.2%. Annino and co-workers [112] investigated the electrolytic reduction on mercury of the optically active l-bromo-2,2-diphenylcyclopropanecarboxylic acid and its methyl ester, and also the reduction of l-bromo-l-methyl-2,2-diphenyl-cyclopropane in neutral, acidic, and alkaline ethanolic solutions. It was found that reduction of the acid took place with 26-35% inversion of the configuration in acidic solutions and with 31-38% retention in alkaline solutions. Reduction of methyl l-bromo-2,2-di-phenylcyclopropanecarboxylate took place with 30-56% inversion of the configuration irrespective of the composition of the solution, whereas reduction of l-bromo-l-methyl-2,2-diphenylcyclopropane took place with 21% retention. These results can be explained on the assumption that the molecule is subject to attack by electrons from the side of the halogen atom and that the whole stereochemistry of the process is determined by stereoselective reaction with proton donors of the free carbanion or of the carbanion screened by the electrode. 

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