Synthesis of Cyclopropane Derivatives

The photoelimination of nitrogen from 1-pyrazolines is one of the most thoroughly investigated photoreactions and it has been used extensively in the synthesis of cyclopropane derivatives.334 Both stereospecific and non-stereospedfic processes have been observed and these are believed, at least in simple 1-pyrazolines, to correspond to singlet and triplet excited states, respectively. Two reaction pathways have been proposed in the azoalkane 405335 direct excitation via a thermally activated S, state affords the C6H6 isomers 406 to 409, whereas triplet-sensitized excitation results in a tem-... 

Sulfur ylides are among the most interesting carbon nucleophiles and their synthetic importance has been recently reviewed.One especially interesting use of these ylides is their application to the synthesis of cyclopropane derivatives using unsaturated oxazolones. For example, stabilized sulfur yhdes react with unsaturated oxazolones 629 via a Michael reaction to give oxazolone spirocyclopropanes 630 as shown in Scheme 7.202 and Table 7.46 (Fig. 7.57), whereas the less stabilized sulfur ylides give ring-opened products 631 as the major compounds (Scheme 7.202). ... 

Starting from optically active 1-chlorovinyl p-tolyl sulfoxide derived from 2-cyclohex-enone, the asymmetric synthesis of cyclopropane derivative (85) was realized (equation 23) . Addition reaction of lithium enolate of tert-butyl acetate to 83 gave the adduct (84) in 96% yield with over 99% ee. Treatment of the latter with i-PrMgCl in a similar way as described above afforded optically pure (15,6/ )-bicyclo[4.1.0]hept-2-ene (85) in 90% yield. 

This method is generally applicable to the stereospecific synthesis of cyclopropane derivatives from a large variety of substituted olefins.4... 

Different allyl 2-lithioaryl ethers underwent a tandem carbolithiathion/y-elimination in Et20/TMEDA, affording o-cyclopropylphenol derivatives in a diastereoselective manner. The use of (-)-sparteine as a chiral ligand instead of TMEDA allowed the synthesis of cyclopropane derivatives with up to 81% ee. The following scheme illustrates this stereoselective process for the formation of chiral o-cyclopropylphenols <02OL2225>. 

Baizer et al. (1972) extensively studied the electroreduction of carbon tetrachloride in the presence of electrophiles for synthetic purposes. Since then the formation of the dichloro-dianion (CCl ) or -carbene (Takita et al. 1990) was considered for the synthesis of cyclopropane derivatives. Recently, carbene formation was observed in the direct reduction of CC14 and DDT (1,1 -bis(p-chlorophenyl)-2,2,2-trichloroethane) on hemin-modified TiC>2 supports (Stromberg et al. 2006). 

These reagents are key intermediates in synthesis of cyclopropane derivatives. The structure and stereochemistry of lithium and magnesium cyclopropyl derivatives as well as their extensive use in organic synthesis have been thoroughly reviewed in previous and updated volumes of this series and no attempt will be made to elaborate on their chemistry here. Their extreme importance in the organometallic chemistry of cyclopropanes will be further revealed as this chapter progresses. 

The introduction of carbenes and carbenoids into synthetic organic chemistry revolutionized the synthesis of cyclopropane derivatives In particular, cyclopropanation of methylenecycloalkanes became a very useful method for the preparation of SPC. Moreover, since cycloaddition of carbenes to olefins involves a very fast concerted process (i.e. it eliminates any intermediates during the formation of the three-membered ring) the method is equally efficient for the preparation of both unstrained and highly strained compounds. 

The cycloaddition of carbenes to olefins is a classical synthesis of cyclopropane derivatives. 

The inherent energy content of the cyclopropane ring demands that the method of introduction of a cyclopropyl subunit itself relies either on highly reactive intermediates or on irreversible or energetically, if not entropically, favored processes. Thus the synthesis of cyclopropane derivatives can be classified into three major categories 1,3 bond forming sequences (equation 4) carbene or carbenoid routes (equation 5) and rearrangement pathways (equations 6 and... 

The procedures for the synthesis of cyclopropane derivatives, especially by the carbenoid route - " 49,55-57 Q, (ijg yjjjjg jQute (l.S-displacement), - have been amply reviewed. Equally well reviewed are the reactions of cyclopropanes and their use in synthetic methodologyFor the preparation of the more common cyclopropane derivatives, the use of suitably functionalized cyclopropyl building blocks that are commercially available would be recommended. 

In contrast to the wealth of chemistry reported for catalyzed reactions of diazocarbonyl compounds, there are fewer applications of diazomethane as a carbenoid precursor. Catalytic decomposition of diazomethane, CH2N2, has been reported as a general method for the methylenation of chemical compounds [12]. The efficacy of rhodium catalysts for mediating carbene transfer from diazoalkanes is poor. The preparative use of diazomethane in the synthesis of cyclopropane derivatives from olefins is mostly associated with the employment of palladium cat-... 

Silver-initiated ring cleavage of bicyclo[1.1.0]butanes in protic solvents leads predominantly to mixtures of cyclopropanes and the corresponding dienes, e.g. a mixture of the norcarane ether 32 and the corresponding homoallylic ether 33 is observed in the reaction of 2,6-dimethyl-tricyclo[4.1.0.0 ]heptane (31) with silver perchlorate. This reaction is of little practical value for the synthesis of cyclopropane derivatives from bicyclo[1.1.0]butanes. 

Synthesis of cyclopropane derivatives. The cyclization of hydroborated allylic chlorides was discovered by Hawthorne and Dupont.7 The major difficulty is that two isomeric boron derivatives are formed in roughly equal amounts, and only one is converted into a cyclopropane. Use of the more selective hydro-borating reagent disiamylborane (1, 57-59 2, 29 this volume) circumvented this... 

Vinylsilanes 132 have been reacted with bromomalononitrile to yield the intermediate 133, which was used for the synthesis of cyclopropane derivatives Addition reactions of dichloromalononitrile with substituted alkenes and alkadienes can also be used for the preparation of intermediates in carbo- and heterocyclic synthesis. 2-Arylmalononitriles 135 have been produced by coupling malononitriles with aryllead(IV) triacetates like 134163. 

In addition to its occurrence in many natural and bioactive products, cyclopropanes are key moieties in many important reactions, due to its inherent ring strain. Thus, the asymmetric synthesis of cyclopropane derivatives is the subject of intense research activity. The most widely enantioselective methods are the transition metal (mainly copper or... 

Dihalocarbenes are also frequently employed in the synthesis of cyclopropane derivatives from alkenes. Most reactions of dihalocarbenes are stereospecific ... 

From Diazo-compounds. The addition of diazo-compounds to olefins provides a routine method for the synthesis of cyclopropane derivatives. The reaction can pro-... 

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