Product-Induced Distortion of a Metalloporphyrin Host:  Implications for Acceleration of Diels−Alder Reactions

Abstract

New cyclic metalloporphyrin hosts, 6 and 7, have been prepared. At 0.33 mM in dichloromethane at 25°C, they accelerate 65-fold and 840-fold respectively the reaction of diene 1 and dienophile 2 and also bind the hetero Diels-Alder product 3 very strongly. More importantly, small single crystals of solvated 6, 7, and the 6 . 3 complex were grown and their structures were determined. As the Diels-Alder product resembles the Diels-Alder transition state, the structures of the product-free host 6 and the 6‚3 host-product complex allow, for the first time for synthetic receptors, a detailed structural analysis of the geometrical changes imposed on an accelerating agent on binding of a Diels-Alder product. Comparison of these structures reveals that when the Diels-Alder product 3 is bound within the cavity, it induces significant structural changes in 6. This provides the first crystallographic structural evidence that accelerated product formation can be accompanied by substantial host distortion. Desolvation of host and guests emerges as another factor, implying that solvent stabilization is not as significant for the host-accelerated reaction as in the control (host free) reaction.

Templated Synthesis of Interlocked Molecules

“…Clipping of isophthalaldehyde 64 occurs at an intermediate rate. This reactivity scale is consistent [183][184][185][186][187][188][189][190][191][192][193][194][195] with the electrophilicities of the different formyl groups.As expected, the dialdehyde 57 exhibits the most electrophilic behavior, while 65 exhibits the least. The donor-acceptor nature of the dumbbell-shaped dialkylammonium ion also affects the rates of clipping.…”

“…Although the imino groups of the interlocked structures are not as accessible sterically as those in free macrocycles or acyclic species, the presence of the NH 2 + center in the rotaxanes provides a mildly acidic environment for the addition of the B-H bond to these particular imines, thereby catalyzing their reduction. The whole process, namely, thermodynamic formation of the diimine [2]rotaxane followed by kinetically controlled borane reduction, is somewhat reminiscent of enzyme catalysis [186] and also catalysis employing synthetic enzyme mimics (for an example of a synthetic receptor with enzyme-like activity, see [187]), wherein an initial recognition process results in a substrate pre-organization and hence access to a conformation that lowers the activation barrier for the final reaction.…”

Adventures in molecular recognition. The ins and outs of templating

“…The first step should be accelerated by our porphyrin oligomers, while the second step should lead to a dramatic geometry change, weaker binding, and, therefore, catalytic turnover. We have been unable as yet to achieve the second step (and therefore turnover) cleanly in the presence of porphyrins, but the first step is successfully accelerated by the same trimers as above and by a range of capped dimers [7,8].…”

“…We have obtained tiny crystals of these new dimer hosts with and without the Diels-Alder adduct in the cavity and have obtained crystal structures using a synchrotron X-ray source [8,9]. We are trying to build up a complete structure-activity relationship by combining solution-state kinetics and thermodynamics with crystal structures; Fig.…”

Reversal of Regioselectivity and Enhancement of Rates of Nitrile Oxide Cycloadditions through Transient Attachment of Dipolarophiles to Cyclodextrins

“…[15] Complexation of the catalysts was found to increase their turnover numbers by up to 100-fold. Sanders and co-workers have also exploited metalloporphyrin cyclic oligomers as artificial enzymes, to accelerate Diels-Alder reactions by several orders of magnitude [6][7][8][9][10] and manipulate the ratio of formation of endo and exo cycloadducts. [6,7] Although large rate accelerations were observed, substrate turnover was negligible because the reaction products had a strong affinity for the host species.…”