Ring opening reactions cyclopropanes, stereochemistry

The ring-opening reactions of cyclopropane and its derivatives with electrophiles (Eq. (1)) are especially interesting from a mechanistic point of view because they involve electrophiUc cleavage of a carbon-carbon single bond. They thus present problems of stereochemistry and the effect... 

Cyclopropanes can undergo attack by electrophiles with either inversion or retention of configuration at the carbon to which the electrophile becomes attached. The stereochemistry at this center, plus the fact that the nucleophile enters with inversion in nearly all cases, can best be accounted for by an intermediate, corner-substituted cyclopropane for many ring-opening reactions. In some cases a direct, single step process may compete with this mechanism. The possibility of an edge-substituted cyclopropane as a reaction intermediate under special circumstances cannot be ruled out at present. 

The stereochemistry of the ring-opening reaction of exo- and e (7o-tricyclo[3.2.1.0 " ]octane 41 by proton, deuterium and mercury(II) ions has been investigated. When the e t/o-isomer was treated with methanol in the presence of a catalytic amount of p-toluenesulfonic acid, endo-2-methoxybicyclo[3.2.1]octane (42a) was obtained in high yield. The exo-compound reacted in an analogous fashion to give exo-2-methoxybicyclo[3.2.1]octane (44a) as the major product and exo-2-methoxy- yn-7-methylbicyclo[2.2.1]heptane (45 a) which resulted from the cleavage of an outside cyclopropane bond. 

Mechano-Stereochemistry of Cyclopropane Ring-Opening Reactions... 

Substituted cyclopropane systems also undergo nucleophilic addition of suitable solvents (MeOH). For example, the photoinduced ET reaction of 1,2-dimethyl-3-phenylcyclopropane (112, R = Me) with p-dicyanobenzene formed a ring-opened ether by anti-Markovnikov addition. The reaction occurs with essentially complete inversion of configuration at carbon, suggesting a nucleophilic cleavage of a one-electron cyclopropane bond, generating 113. The retention of chirality confirms that the stereochemistry of the parent molecule is unperturbed in the radical cation 112 " ". 

Irradiation of a mixture of diphenyl disulfide and diphenyl ditelluride in the presence of vinyl cyclopropane 141 with visible light gives the ring-opened thiatelluration product 142 as an E/Z mixture.208 Similar reaction with alkynes gives the thiatelluration product 143. The product stereochemistry depends on the nature of the alkyne.208 A mixture of diphenyl diselenide and diphenyl ditelluride reacts with alkynes in a similar way (Scheme 78).208 Similar reactions with allenes are less satisfactory.209... 

Unlike intermolecular cyclopropanation reactions, the intramolecular version is stereo-specific with respect to the configuration of both, the C-C double bond and (due to steric constraints) the carbenoid center. This fact can be used for the directed synthesis of cis-1,2-disubstituted, all-ci. -l,2,3-trisubstituted or d. , ra . -l,2,3-trisubstituted cyclopropanes. For example, a-diazo esters (a-diazocarboxamides) with an unsaturated ester (amide) residue yield bicyclic lactones (lactams) stereospecifically which can be ring opened to give the monocyclic cyclopropanes mentioned with defined stereochemistry. Some possibilities are illustrated by the examples, 20 -+ 22 -> 23, and 24 25. ... 

Mechanistic aspects of the electrophilic cleavage of cyclopropanes by metal salts have received considerable attention. Studies of the stereochemistry of reactions of cyclopropanes with mercuric trifluoroacetate lead to the conclusions that the electrophilic mercuric ion attacks the least strained ring bond (for equally substituted bonds, attack is preferred at a cis-substituted bond over a trans-substituted one). Ring-opening occurs in the direction of the more stable carbonium ion, which can lead... 

Scheme 10.15, which is appreciably shorter than 10.14, uses the same general methods to establish the stereochemical relationships. In step C, the cyclopropane ring is opened by protonation. The incipient carbonium ion is captured intramolecularly, and the cis relationship between the C-2 and C-5 substituent is thereby established. The geometry of the bicyclic ring system and the retention of stereochemistry in the Baeyer-Villiger reaction are used to ensure the cis stereochemistry of the substituents at C-1 and C-3, as in Scheme 10.14. Step A is an electrophilic substitution that is initiated by protonated formaldehyde. The resulting cation is captured by formic acid, and the primary alcohol is also formylated under the reaction conditions.

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