Cyclopropane derivatives, synthesis

CYCLOPROPANECARBOXYLIC ACID, cis-2-PHENYL-, 50, 94 Cyclopropane derivatives, synthesis, 52, 22, 33, 132 Cyclopropenes, 50, 30 Cyclopropenone, di-tert-buty1-,... 

Trifluoromethylzinc compounds can be prepared via the direct reaction of dihaloditluoromethane with zinc powder in DMF [J5] (equation 24) In this reaction, the DMF functions both as solvent and reactant Mechanistic experiments support a difluorocarbene reaction intermediate Indeed, a mixture of zinc and difluorodibromomethane in THF has been used for the synthesis of gewi-difluo-ro-cyclopropane derivatives [34 (equaUon 25)... 

Alkenylcarbene complexes react with in situ-generated iodomethyllithium or dibromomethyllithium, at low temperature, to produce cydopropylcarbene complexes in a formal [2C+1S] cycloaddition reaction. This reaction is highly diastereoselective and the use of chiral alkenylcarbene complexes derived from (-)-8-phenylmenthol has allowed the enantioselective synthesis of highly interesting 1,2-disubstituted and 1,2,3-trisubstituted cyclopropane derivatives [31] (Scheme 9). As in the precedent example, this reaction is supposed to proceed through an initial 1,4-addition of the corresponding halomethyllithium derivative to the alkenylcarbene complex, followed by a spontaneous y-elimi-nation of lithium halide to produce the final cydopropylcarbene complexes. 

Pagenkopf s group developed a novel domino process for the synthesis of pyrroles 4-183, which allows for the control over the installation of substituents at three positions and seems to be very suitable for combinatorial chemistry [62]. The process consists of a 1,3-dipolar cycloaddition of an intermediate 1,3-dipole formed from the cyclopropane derivative 4-181 with a nitrile to give 4-182 followed by dehydration and isomerization (Scheme 4.39). The yield ranges from 25 to 93 %, and the procedure also works well with condensed cyclopropanes. 

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-... 

The chemistry of a-haloketones, a-haloaldehydes and a-haloimines Nitrones, nitronates and nitroxides Crown ethers and analogs Cyclopropane derived reactive intermediates Synthesis of carboxylic acids, esters and their derivatives The silicon-heteroatom bond Syntheses of lactones and lactams The syntheses of sulphones, sulphoxides and cyclic sulphides... 

His research interests deal with the chemistry of cyclopropane derivatives, 1,3-dipolar cycloadditions, synthesis of natural compounds and biologically active analogues. Recently, the research activity is also dedicated to synthetic studies for the production of new materials light-harvesting antenna systems and functionalized organogelators. 

A second example of the use of ionic chiral auxiliaries for asymmetric synthesis is found in the work of Chong et al. on the cis.trans photoisomerization of certain cyclopropane derivatives [33]. Based on the report by Zimmerman and Flechtner [34] that achiral tmns,trans-2,3-diphenyl-l-benzoylcyclopropane (35a, Scheme 7) undergoes very efficient (0=0.94) photoisomerization in solution to afford the racemic cis,trans isomer 36a, the correspondingp-carboxylic acid 35b was synthesized and treated with a variety of optically pure amines to give salts of general structure 35c (CA=chiral auxiliary). Irradiation of crystals of these salts followed by diazomethane workup yielded methyl ester 36d, which was analyzed by chiral HPLC for enantiomeric excess. The results are summarized in Table 3. 

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. 

The enantioselective cyclopropanation leading to 1,2,3-snbstitnted cyclopropane derivatives proceeds with high diastereocontrol (equation 86) . It is quite interesting to observe that the same reaction, when run in the absence of the dioxaborolane ligand, led to lower diastereoselectivity. Other functionalized 1,1-diiodoaLkanes can be used as the zinc carbenoid precursor, but it should be noted that up to 2 equivalents of the reagent (4 equivalents of RCHI2) are needed in this process. This reaction has been applied in the synthesis of ambruticin. ... 

Cyclopropane derivatives, including spiropentanc, have proven to be virtually inert towards carbenes,1 For this reason, no literature report that describes cyclobutane synthesis from a C3 and a Cj building block by ring enlargement of cyclopropanes exists. However, due to the partial p character, as well as the increasing reactivity caused by its strain, the central bond of bicyclo[1.1.0]butane (l)2 has been found to react with carbenes.1 Photolysis of diazomethane in the presence of bicyclo[1.1.0]butane (1) at — 50 C provides a mixture of several compounds. The major fraction of the material (80%) was analyzed by means of NMR spectrometry and found to consist of penta-1,4-diene (2, 21%) and bicyclo[l.l.l]pentane (3, 1%), plus several other known compounds as well as some unidentified products.3 The mechanistic pathway for the formation of bicyclo[l.l.l]pentane (3) has not been addressed in detail, but it is believed that a diradical intermediate is involved, as shown below.3... 

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

Particularly interesting applications of isopropylidenediphenylsulfuran [459, 464] have been reported. Improvements in its preparation and use led [465] to a claimed industrially viable stereoselective synthesis of Deltamethrin, the most potent commercially available insecticide, as well as to other stereoselective syntheses of cyclopropane derivatives [466]. 

The inclusion of a separate chapter on catalysed cyclopropanation in this latest volume of the series is indicative of the very high level of activity in the area of metal catalysed reactions of diazo compounds. Excellent, reproducible catalytic systems, based mainly on rhodium, copper or palladium, are now readily available for cyclopropanation of a wide variety of alkenes. Both intermolecular and intramolecular reactions have been explored extensively in the synthesis of novel cyclopropanes including natural products. Major advances have been made in both regiocontrol and stereocontrol, the latter leading to the growing use of chiral catalysts for producing enantiopure cyclopropane derivatives. 

KISHNEK CYCLOPROPANE SYNTHESIS. Formation of cyclopropane derivatives by deeompoxiiion of pyra/olines formed by reacting tr/l-unsiiiurated kelones or aldehydes with hydrazine. 

Elimination reactions of this type can be useful in synthesis for the formation of carbon-carbon bonds. For example, if dibromocarbene is generated in the presence of an alkene, it will react by cycloaddition to give a cyclopropane derivative ... 

Another type of chiral Michael acceptor, the oxazepine derivatives (47), is prepared by condensation of the (-)-ephedrine-derived malonic acid derivative (46) with aldehydes (Scheme 18).51 52 Treatment of (47) with a variety of Grignard reagents in the presence of NiCh affords, after hydrolysis and decarboxylation, the 3-substituted carboxylic acids (48), in most cases with more than 90% ee. Diastereoselective Michael additions to (47) were also used for the preparation of optically active cyclopropane derivatives (49)53 and P-substituted-y-butyrolactones (50 Scheme 18).54 A total synthesis of indolmycin is based on this methodology.55... 

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