Cyclopropanation. alternative methods

Treatment of geminal dihalocyclopropyl compounds with a strong base such as butyl lithium has been for several years the most versatile method for cumulenes. The dihalo compounds are easily obtained by addition of dihalocarbenes to double--bond systems If the dihalocyclopropanes are reacted at low temperatures with alkyllithium, a cyclopropane carbenoid is formed, which in general decomposes above -40 to -50°C to afford the cumulene. Although at present a number of alternative methods are available , the above-mentioned synthesis is the only suitable one for cyclic cumulenes [e.g. 1,2-cyclononadiene and 1,2,3-cyclodecatriene] and substituted non-cyclic cumulenes [e.g. (CH3)2C=C=C=C(CH3)2]. 

Because of the unique properties of the cyclopropane ring, cyclopropylbenzene is a compound of considerable interest. Only one of the alternative methods 9 for the preparation of this compound has been reported to give more than 32% yield the procedure described affords an olefin-free product without a relatively laborious purification process. By its utilization of readily available starting materials, and by its applicability to the preparation of large quantities of product, this method of synthesis provides easy access to many cyclopropylbenzene derivatives.12... 

Asymmetric allylic C-H activation of more complex substrates reveals some intrinsic features of the Rh2(S-DOSP)4 donor/acceptor carbenoids [135, 136]. Cyclopropanation of trans-disubstituted or highly substituted alkenes is rarely observed, due to the steric demands of these carbenoids [16]. Therefore, the C-H activation pathway is inherently enhanced at substituted allylic sites and the bulky rhodium carbenoid discriminates between accessible secondary sites for diastereoselective C-H insertion. As a result, the asymmetric allylic C-H activation provides alternative methods for the preparation of chiral molecules traditionally derived from classic C-C bond-forming reactions such as the Michael reaction and the Claisen rearrangement [135, 136]. 

Neither CS2 nor TMS are ideal standards. The 13C signals of CS2 and carbonyl carbons overlap, as do the 13C signals of cyclopropane and some methyl carbons with TMS (Fig. 3.3). Furthermore, the 13C resonance of TMS has been shown to suffer from solvent shifts of the order of + 0.1 to 1.5 ppm in common NMR solvents, even at infinite dilution [74]. This must be considered if 13C shifts relative to TMS of one compound in different solvents are to be compared. There are two alternative methods to overcome this problem one is to use cyclohexane as the internal reference cyclohexane was shown to have 13C solvent shifts lower than + 0.5 ppm [74], The other alternative is to use TMS as an external reference (Sections 1.9.3 and 2.8.5) and to make bulk susceptibility shift corrections according to eq. (1.44). 

In disubstituted cyclopropanes, cyclobutanes and cyclopentanes, assignment of configuration, cis or trans, is made with respect to a plane through the molecule. Cyclopentanes and most cyclobutanes are not planar, but this does not pose a significant problem. Cyclohexanes are also non-planar. Using the above method it can take a while to decide whether the relative configurations of some disubstituted cyclohexanes are cis or trans. For these compounds we employ an alternative method based on dihedral angles. 

Ring synthesis by radical-radical coupling, as well as intramolecular radical substitution, is an alternative method for producing rings, which does not rely on the addition of a radical to an unsaturated bond. Cyclopropanes have been prepared from diiodides by the reaction of a catalytic amount of a fluorinated tin hydride with NaCNBHs in a fluorinated-organie solvent mixture. The rate constant for the reaction was determined using PhsSiH as a chain carrier and found to be 5 x 10 at 80 °C (Scheme 18). The cyclization of 2,2-diethylpropane-1,3-thiol and 4,4-diethyl-1,2-dithiolane in the presence of 2,5-dimethylhexa-2,4-diene and AIBN has been shown to proceed via a radical-chain mechanism (Scheme 19). ... 

An alternative synthetic approach, first developed by Bingel225 allowed the efficient nucleophilic cyclopropanation of fullerenes via their reaction with bromomalonate derivatives in the presence of base. This approach, the most reliable method for the synthesis of functionalized methanofullerenes, combined the advantages of mild... 

Electrochemical cyclopropanation of alkenes occurs using dibromomethanes at a sacrificial zinc electrode in a CH2C12/DMF mixture with a one compartment cell (equation 65). Yields using more than twenty isolated and conjugated olefins were generally good (30 to 70%)98. Benzal halides give only poor yields in the same reaction, but 2,2-dibromo-propane leads to the equivalent gem-dimethylcyclopropanes in fair yields. The method represents a useful alternative to other methods of cyclopropanation of olefins such as the Simmons-Smith reaction. 

An alternative to the Simmons-Smith and Furukawa reagents is iodomethylzinc phenoxide, readily accessible by deprotonation of phenol with Et2Zn and subsequent metal-halogen exchange with CH2l2- An economically attractive method for cyclopropanation of alkenes is to use CH2Br2, which is considerably less expensive and easier to purify and store than CH2l2- ... 

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