Rearrangements, Claisen rate acceleration with

A kinetic study of the Cope rearrangement of 2-(trifluoromethyl)oeta-l.5-diene [(Z)-7] showed no rate acceleration in comparison with the rearrangement of unsubsliluled hexa-1,5-diene. Equilibrium was reached after 7 days at 207 C (K = 3.46 favoring the is-isomer). at which stage no intermediate 4-ethylhcxa-l,5-diene 8 was observed.6 In contrast, a trifluoromethyl group at position 2 does accelerate the Claisen rearrangement (sec Section 5.1.5.2.). 

A second general approach to allyl /(-lluorovinyl ether intermediates involves the reaction of a /J-fluoro alcoholate with an allylic halide. Claisen rearrangement then produces a-fluoro carbonyl compounds. Although the tremendous rate acceleration caused by a-fluoro substitution in the vinyl fragment is not present here, the rearrangements take place under synthetically useful conditions. 

It can be seen from the examples displayed above that the Claisen rearrangement of allyl vinyl ethers with an amino substituent at C(n and C(2) proceeds much faster than that of allyl vinyl ether itself. Several models98- 00 have been proposed in order to interpret the substituent effect on the rate of Claisen rearrangement. Both the acceleration of the rearrangements of / -allyloxyenamine and 0-allylketene TV, 0-acetals and deceleration of the reaction of enamine 120 are in agreement with the prediction of the models. 

Another new development in enzymatic reactions is the use of monoclonal antibodies as catalysts. These antibodies show regio- and stereoselectivity, substrate specificity, and rate acceleration. Hilvert12 has discussed three different reactions that are catalyzed by these antibodies decarboxylation, Dicls-Alder reactions, and Claisen rearrangements. This catalysis is a new field with tremendous possibilities. 

Numerous organic reactions have been studied in aqueous solutions. It was observed that water is able to induce dramatic rate accelerations in Diels-Alder cycloadditions [66], benzoin condensation [67], Claisen rearrangements [68], Mu-kaiyama aldol reactions [57], Michael reactions [69], Baylis-Hillman reactions [70], and 1,3-dipolar cycloadditions [71], All these reactions are characterized by negative volume changes and negative volumes of activation. It is expected that ground state destabilization in aqueous media associated with transition state stabilization is one of the determining kinetic factors. 

Many charge-accelerated reactions have been observed in [3,3] sigmatropic rearrangements [10], In the Claisen-Johnson rearrangement, a combination of micro-wave irradiation and acidic catalysis (KSF day) has been used successfully by Jones with several cyclic allylic alcohols [1 Ij. Rate acceleration (9 min versus 12.5 h for conventional heating) and better yields were observed (Scheme 6.3). 

There have been two recent analyses of the hydration effeas on the Claisen rearrangements among previous studies, one using the SCRF AMI-SM2 model by Cramer and Truhlar, and the other employing Monte Carlo simulation with die OPLS potential by Severance and Jorgensen. The two methods are complementary to each other, in that the former calculation indudes the molecular electronic polarization whereas the latter treats solute-solvent intermolecular interactions explicidy. Cramer and Truhlar reported a rate acceleration of 21-fold, or a AAGl j of —1.6 kcal/mol, for allyl vinyl ether... 

In the course of biomimetic total synthesis of gambogin, Nicolaou reported a dramatic rate acceleration in water of the Claisen rearrangement of 138 to 139 (Scheme 5.45). ° In ds-benzene at 100°C there was no detectable reaction, while in dy-DMF and MeOH the rearrangement was complete in 30 min. The use of water (MeOH/HyO 1 1) reduced the reaction time in half The authors also report the first examples of a Claisen-Diels-Alder cascade sequence (140 141 142) accelerated by aqueous medium. In this case, the beneficial effect of water with respect to dy-DMF was even greater. 

---