Cyclopropane direct steric effects

These effects can occur when the active site at which a measurable phenomenon occurs is in close proximity to the substituent. Among the many systems exhibiting direct steric effects are ortho-substituted benzenes, 1, cis-substituted ethylenes, 2, and the ortho- (1,2-, 2,1- and 2,3-) and peri- (1,8-) substituted naphthalenes, 3, 4, 5 and 6, respectively. Other examples are d.v-1,2-disubstiUited cyclopropanes, c/ s-2,3-disubstituted norbornanes and ci.s-2,3-disubstituted [2.2.2]-bicyclooctanes, 7, 8 and 9, respectively. Some systems generally do not show steric effects. Vicinally substituted systems such as disubstituted methanes, 10, and 1,1-disubstituted ethenes, 11, are examples, 2,3-Disubstituted heteroarenes with five-membered rings such as thiophenes and selenophenes... 

Homoallylic nucleophilic substitution is known (equation 23), but its synthetic utility is hampered by competing direct substitution without opening of the cyclopropane ring. The product ratio is largely influenced by the nature of the attacking nucleophile and the cyclopropane substituents (steric effects). ... 

The cyclopropanation is sensitive to steric effects, adding from the less-hindered face. Having a neighboring hydroxyl group will generally accelerate the reaction, and will direct the cyclopropanation syn to the hydroxyl group even into sterically congested alkenes. 

Palladium-catalyzed methylene transfer from diazomethane has proved effective for the cyclopropanation of 1-alkenylboronic acid esters allylic alcohols and amines 1-oxy-l,3-butadienes and allenes " Readily accessible iron complex (CO)2FeCH2S Me2 BF4 35 undergoes direct reaction with a range of alkenes to give cyclopropanes (equation 67) The salt is sensitive to steric effects and the reaction proceeds... 

The main products in the reaction mixtures of the 2,2-dimethylcyclopropyl ketone 39 and the cis-2-methylcyclopropyl ketone cis-40, respectively, result from C-l-C-2 bond breaking. In contrast, the frartj-2-methylcyclopropyl ketone trans-41 breaks the C-l-C-3 bond. This strongly suggests that steric factors control the direction of cleavage, presumably through asymmetric overlap of the carbonyl 7r-system with one of the cyclopropane bonds 43). In the absence of these steric effects, as in trans-41, the bond that cleaves is the one to give the more thermodynamically stable (= less substituted) carbanion intermediate. 

The geminal bis-(ethoxycarbonyl)-substituted cyclopropane 26 effectively countered the steric problem to give cleavage at the more highly substituted C—C bond (Scheme The nitrogen atom may also have assisted in directing this C—C bond cleavage. 

Wender s group has also developed rhodium-catalyzed intermolecular [5-1-2] cycloadditions. At first, they found the catalysis system of Rh(PPh3)3Cl for the intramolecular reactions was not effective at all for the intermolecular reactions. To effect the intermolecular [5-1-2] cycloadditions, [Rh(CO)2Cl]2 must be used and oxygen substitution of the cyclopropane was necessary (see (17)) [37-39]. Then they successfully expanded the substrate to unactivated vinylcyclopropanes by adjusting the substituents. For monosubstituted alkynes, the substitution on the olefin terminus directs the formation of single isomer that minimized steric hindrance (see (18)) [40]. The [5-1-2] cycloadditions can also be applied to VCPs with allenes (see (19)) [41]. It should be noted that the alkyne substituent did not interfere with the reaction, indicating that allenes as reaction partners were superior to alkyne in the [5-1-2] cycloadditions. Curiously, the authors didn t report the corresponding intermolecular [5-1-2] cycloadditions of VCPs with alkenes. 

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