Structure-activity relationships in the acceleration of a hetero Diels-Alder reaction by metalloporphyrin hosts.
At 0.33 mM in dichloromethane at 25 degrees C the cyclic metalloporphyrin hosts 5, 7, 8, and 10 accelerate 12-fold, 260-fold, 1130-fold, and 250-fold, respectively, the reaction of 1 and 2 and also bind the product 3 very strongly. These observations combined with previously measured results with hosts 6, 9, and 11 allowed us to explore the influence of host geometry changes on acceleration rates and product binding over a wide range of host molecules of different size, ranging from extremely tightly strapped to very relaxed. To estimate the Zn-Zn distance in the transition-state complex, we carried out quantum mechanical calculations (at the HF/6-31G level) for the transition state to form 3. The structure-activity relationships found for hosts 5-11, along with the structural features calculated for the transition-state structure between 1 and 2 and previously crystallographically observed for product-free hosts and for a host.product complex,(4) suggest that both host preorganization as well as host flexibility are key features leading to high acceleration rates and product binding and that it is the delicate balance between the two structural features that leads to maximum efficiency.
Nakash
M
M
Cambridge Centre for Molecular Recognition, University Chemical Laboratory, Lensfield Road, Cambridge CB2 1EW, UK.
Sanders
J K
JK
D002384:Catalysis; D018360:Crystallography, X-Ray; D007700:Kinetics; D008665:Metalloporphyrins / Q000737:chemistry*; D008968:Molecular Conformation; D009010:Monte Carlo Method; D011789:Quantum Theory; D013329:Structure-Activity Relationship
D008665:Metalloporphyrins