Tetrasubstituted cyclopropanes

Tetrathia[6.6.1]propellane 72 has been prepared 21. This is the parent of the dibenzo compound 7/just mentioned 20). The same tetrasubstituted cyclopropane 24 was used, this time simply with 1,2-ethanedithiol, under conditions of high dilution... 

The most widely explored method is the formation of tri- and tetrasubstituted cyclopropanes by reaction of vinylsulfonium salts with methylene compounds activated by ester, ketone, nitrile, or sulfone substituents. A series of examples is collected in Table 25. A variant of this method, where cyclopropanedicarboxylates cis-1 were actually obtained by intramolecular cyclization of the sulfonium salt Cj building block is also shown.Alkylthiocyclopropane derivatives 8 were obtained by the reaction of a ketene dithioacetal monosulfonium salt with carbanions derived from doubly activated methylene compounds. ... 

Thermolysis of 1-substituted 3,3-dialkoxycyclopropanes regioselectively gives disubstituted carbenes which provide tri- and tetrasubstituted cyclopropane derivatives related to 8 with excellent cis selectivity18. 

Many studies of substituent effects on radical stabilization involved C-C homolysis reactions leading to rather similar diradicals. Cis-trans isomerization of tetrasubstituted cyclopropanes 24 (Scheme 5) is found to occur fastest when the intermediate diradical 25 is stabilized by captodative substitution [25], with better donors yielding faster reactions. 

Cinchonidine (99) has extended the substrate scope of the ketone conjugate additions to P-substituted methylidene malononitriles. In particular, the reaction of a-chloromethyl ketones, under very low loading conditions, affords tetrasubstituted cyclopropanes in moderate to good enantioselectivities after intramolecular cycliza-tion (Scheme 2.45) [142], A similar strategy has been followed to synthesize, with moderate to good enantioselectivities (56-90% ee) optically active naphlhopyran derivatives by a conjugate addition/cyclization sequence between 2-naphthol and a,a-dicyanoolefins [ 143 ]. 

Disubstituted-a-bromocyclopropylcarboxamides eliminate HBr when treated with t-BuOK and 18-crown-6 ether in DMSO (dimethyl sulfoxide) at 40 °C, forming a cyclo-propene intermediate that adds an alcohol (nucleophile) at C(3) on the least hindered face of the cyclopropene ring. This is followed by an epimerization at C(l) forming (g) the most stable product, that is, a tra 5 -l,2,2,3-tetrasubstituted cyclopropane. The position of the nucleophile on C(3) is determined by the size of the groups on C(2) and the stereochemistry of the final addition product trans-) is determined by the epimerization at C(l). Two procedures are used for these reactions, with the best yields from the two methods ranging from 63 to 92% with diasteromeric ratios between 9 1 and 46 1 dr. 

Tetrasubstituted cyclopropanes were prepared by the [2+l]-cycloaddition of 1 with 1,1-bis (alkoxycarbonyl)-2-acyl olefins in the presence of zinc bromide (eq 11). Substitution of the 2-acyl group for a 2-alkyl, aryl, or alkoxy group of the acceptor olefin resulted in diminished yields. A cfr, s-cyclopropane-1,2,3-tricarboxyhc acid was prepared over five steps from 1 in 38% yield as a template for coUagen triple helix formation (eq 12). 

The vinylketene complex [(l) -PhCH=CHC(Bu )=C=0)Fe(C0)3] was reported O to react with electron-poor alkenes to give decarbonylated adducts, characterised crystallogn hically in the case of the adduct with dimethyl fiimarate. Oxidation of the adducts with ceric ammonium nitrate afforded tetrasubstituted cyclopropanes. 

Reaction of ferralactone complexes with amines provides ferralactam complexes. Aromatic amines require the addition of a Lewis acid, whereas alkyl amines react spontaneously. In the course of the reaction, the iron complex moiety moves from one end of the allyl system to the other with concomitant inversion of the configuration at Cl and C4. Reaction of a tricarbonyl(vinylketene)iron complex with electron-deficient alkenes gives (pentenediyl)iron complexes that can be oxidized to tetrasubstituted cyclopropanes. ... 

Chiral dirhodium(II) catalysts with carboxylate or carboxamidate ligands have recently been developed to take advantage of their versatility in metal carbene transformation, and these have now become the catalysts of choice for cyclopropanation. Chiral carboxylate ligands 195,103 196,104 and 197105 have been used for tetrasubstitution around a dirhodium(II) core. However, the enantioselectivity in intermolecular reactions with simple ketenes is marginal. 

For synthetic purpose, the selective preparation of tetrasubstituted enynes was also investigated in the reactions of l-cydopropyl-2-propyn-l-ols bearing a substituent at the a-position in a cyclopropane ring with anilines (Scheme 7.37). As expected, the corresponding tetrasubstituted enynes were obtained in high yields with almost complete selectivity. 

Interestingly, cyclopropane and benzene have the same number of isomers for a given number of identical substituents ignoring optical isomers, cyclopropane and benzene have one type of monosubstituted derivative, three types of disubstituted, three types of trisubstituted, three types of tetrasubstituted and one type apiece of penta- and hexasubstitution. But does this seemingly accidental counting equivalence have any thermochemical consequences ... 

In the presence of alkenes, photolysis of alkyl (silyl)diazoacetates leads mainly to the formation of cyclopropanes as diastereomeric mixtures4,111,112. With (Z)- and ( )-but-2-ene, the cyclopropanation is not completely stereospecific with respect to the double bond configuration, but gives a small amount of the wrong isomer these results point to the participation of a triplet carbene in the cyclopropanation reaction. Allylic C,H insertion products are also formed their yield increases in the series 1,1-, 1,2-, tri- and tetrasubstituted C=C bond. With 2,3-dimethyl-but-2-ene, the allylic C,H insertion product is formed at the complete expense of the cyclopropane. 

When lithium methanetellurolate was used, l,I-bis[methyltelluromethyI cyclopropane was isolated instead of the expected tetrasubstituted methane derivative1. 

Treatment of j]2-iminosilaacyl complex 6c with LiEt3BH gave azazircona-cyclopropane 10, which was hydrolyzed to give (silylmethyl)aniline in 82% yield (Scheme 5). Treatment of 10 with 4-octyne gave alkene 12 in 73% yield after hydrolysis. Presumably, the insertion of alkyne into the carbon-zirconium bond of 10 gives silazirconacyclopentene 11. When CuCl and allyl chloride were added to a THF solution of silazirconacyclopentene 11, tetrasubstituted alkene... 

Pt(II) to the alkyne of the substrate likely triggers all these events. The cycloisomerization might undergo a metallacyclic intermediate that proceeds to eliminate /3-H. The formation of cyclopropanes is presumably succeeded via alkenyl platinum carbene followed by platina(IV)cyclobutane intermediates. The extension using formal metathesis of the enynes includes two transformations, the formation of 1,3-diene moieties and the stereoselective tetrasubstituted aUcene derivatives via O C allyl shift, both leading to diverse structural motifs and serving as the key step in the total synthesis of bioactive targets (Scheme 83). 

The enantioselective cyclopropanation reaction is quite general and practical. For example, the cyclopropanation reaction has been used to synthesize 3-methylcyclopropylmethanol, a precursor to curacin A. Tri- and tetrasubstituted allylic alcohols are also converted into their corresponding cyclopropanes with high enantiocontrol (eq 5). 

Similarly, tetrasubstituted alkene functions can be cyclopropanated selectively in the presence of less highly substituted alkene moieties. These latter reactions require the more potent aminium salt 4+ as the initiator, since simple alkene functions are... 

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