Transition-state interactions yield

As noted previously, noncovalent association between the enzyme and its substrate(s) is the essential first step in biocatalytic reactions. Although early theories of enzyme catalysis focused primarily on interactions between the enzyme and substtate, it was later appredated that maximizing selective, noncovalent interactions between the enzyme and the high-energy uansition state(s) that linked enzyme-bound complexes of substrates and products was the key to efficient rate enhancements. A somewhat oversimplified view is that ground-state interactions determine substrate specifidty and transition-state interactions yield rate enhancements. 

Scheme 28 explains the stereochemical outcome from the tandem radical cyclization in the presence of the [Yb(Ph-pybox)(OTf)3] (pybox = 2,6-bis(2-oxazolin-2-yl)pyridine). The ytterbium complex 107 is shown in an octahedral geometry (with one triflate still bound to the metal) where re-face cyclization is favored due to the steric interactions of the substrate and the ligand s phenyl groups. The 6-endo cyclization takes place via a chair-like transition state to yield a tertiary radical 108 followed by a ring flip and... 

DFT calculations on the Mg(L—H)+ complex also reveal how HNCO might be lost (Scheme 10). Thus the bidentate interaction of the acetamide ligand with Mg in 51 must be disrupted to yield either of the monodentate structures 52 or 54. These intermediates can insert into the CH3—C bond via four-centered transition states to yield the organometallic ions 53 or 55, which can then lose HNCO to form MgCH3+. The DFT calculations reveal that path (A) of Scheme 10 is kinetically favored. 

Combining these two contributions and accounting for reactant-electrode image interactions within the transition state [31b] yields eqn. (19). 

An expedient and stereoselective synthesis of bicyclic ketone 30 exemplifies the utility and elegance of Corey s new catalytic system (see Scheme 8). Reaction of the (R)-tryptophan-derived oxazaboro-lidine 42 (5 mol %), 5-(benzyloxymethyl)-l,3-cyclopentadiene 26, and 2-bromoacrolein (43) at -78 °C in methylene chloride gives, after eight hours, diastereomeric adducts 44 in a yield of 83 % (95 5 exo.endo diastereoselectivity 96 4 enantioselectivity for the exo isomer). After reaction, the /V-tosyltryptophan can be recovered for reuse. The basic premise is that oxazaborolidine 42 induces the Diels-Alder reaction between intermediates 26 and 43 to proceed through a transition state geometry that maximizes attractive donor-acceptor interactions. Coordination of the dienophile at the face of boron that is cis to the 3-indolylmethyl substituent is thus favored.19d f Treatment of the 95 5 mixture of exo/endo diastereo-mers with 5 mol % aqueous AgNC>3 selectively converts the minor, but more reactive, endo aldehyde diastereomer into water-soluble... 

Additionally, it was found that the energy difference between the two transition states (3 and 4) is determined mainly by the difference in the conformational energy of the a-chloro aldehyde in the two transition states i.e., the energetic preference of transition state 3 over 4 is due to a more favorable conformation of the aldehyde rather than a more favorable interaction with the attacking nucleophile. In fact, interaction between lithium hydride and 2-chloropropanal stabilizes transition state 4, which yields the minor diastereomer. 

Polymerization of t-butyl methacrylate initiated by lithium compounds in toluene yields 100% isotactic polymers 64,65), and significantly, of a nearly uniform molecular-weight, while the isotactic polymethyl methacrylate formed under these conditions has a bimodal distribution. Significantly, the propagation of the lithium pairs of the t-Bu ester carbanion, is faster in toluene than in THF. In hydrocarbon solvents the monomers seem to interact strongly with the Li+ cations in the transition state of the addition, while the conventional direct monomer interaction with carbanions, that requires partial dissociation of ion-pair in the transition state of propagation, governs the addition in ethereal solvents. 

In contrast, substrates 149 all furnished [4 + 3]-cycloadducts 150 and 151 in yields ranging from 10-79% (Scheme 34)68. In all cases, exclusive approach of the furan from the zwitterion face opposite the epoxide ring was seen. In most cases, the exo diastereomer 151 was the major product or was formed to the exclusion of the endo diastereomer 150. The contrasting diastereoselectivity seen in inter- and intramolecular cycloadditions may result from unfavorable nonbonding interactions in the endo transition state between the tether atoms and the alkyl groups at C-2 and C-5. 

High oxidation state alkylidene complexes in which a heteroatom is bound to the alkylidene carbon atom are extremely rare [41]. Since the approach shown in Eq. 43 failed, the related approach shown in Eq. 44 was taken to prepare the medium-sized ring subunits [222]. The latter product was formed in good yield when n=2, R H, R2=Et, but only poor yield when n=2, R =Et, R2=H, possibly due to unfavorable interactions between the ethyl substituent and transannular groups in the transition state for cyclization of the allyl ether [222]. Ruthenium catalysts either failed or gave low yields, presumably because of the steric hindrance associated with ring-closing dienes of this type. 

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