Transition states reduction

Kurz, L.C. and Erieden, C. (1977). Comparison of the structures of enzymatic and nonenz3fmatic transition states. Reductive desulfonation of 4-X-2,6-dinitrobenzene-sulfonates by reduced nicotinamide adenine dinucleotide. Biochemistry 16, 5207 -5216... 

Any discussion based on reactivity ratios is kinetic in origin and therefore reflects the mechanism or, more specifically, the transition state of a reaction The transition state for the addition of a vinyl monomer to a growing radical involves the formation of a partial bond between the two species, with a corre sponding reduction of the double-bond character of the vinyl group in the monomer ... 

The single mutation Asp 32-Ala reduces the catalytic reaction rate by a factor of about lO compared with wild type. This rate reduction reflects the role of Asp 32 in stabilizing the positive charge that His 64 acquires in the transition state. A similar reduction of kcat and kcat/ m (2.5 x 10 ) is obtained for the single mutant Asn 155-Thr. Asn 155 provides one of the two hydrogen bonds to the substrate transition state in the oxyanion hole of subtilisin. 

The rho values (2.78 overall, 3.78 for reduction to the cis product and 1.96 for reduction to the trans), determined from a study of the rates of reduction with NaBH4 of a series of 4-substituted cyclohexanones, have been interpreted as supporting a transition state late in the reaction.Other groups have observed positive rho values (2.5 to 3.1) for the reduction with NaBH4 of fluorenones and acetophenones. These results show clearly... 

The relation of rates of reduction with NaBH4 to variations in structure in a wide variety of monocyclic and bridged bicyclic compounds has also been discussed for example, a methyl a to a ketone slows the rate of reduction. Brown ° stated that reactions should not be discussed in terms of axial and equatorial attack, since the rates simply reflect differences in the energies of the possible transition states and not enough is known about the transition state to analyze it. He accepted th concepts of SAC and PDC, but preferred to call them steric strain contrpl and product stability control. ... 

Alteration of the relative reactivity of the ring-positions of quinoline is expected and observed when cyclic transition states can intervene. Quinoline plus phenylmagnesium bromide (Et20,150°, 3 hr) produces the 2-phenyl derivative (66% yield) phenyllithium gives predominantly the same product along with a little of the 4-phenylation product. Reaction of butyllithium (Et 0, —35°, 15 min) forms 2-butylquinoline directly in 94% yield. 2-Aryl- or 6-methoxy-quinolines give addition at the 2-position with aryllithium re-agents, and reaction there is so favored that appreciable substitution (35%) takes place at the 2-position even in the 4-chloroquinoline 414. Hydride reduction at the 2-position of quinoline predominates. Reaction of amide ion at the 2-position via a cyclic... 

Grignard reagents that contain a /3-hydrogen—e.g. 15—can reduce a carbonyl substrate by transfer of that hydrogen as a side-reaction. The so-called Grignard reduction is likely to proceed via a six-membered cyclic transition state 16 the alkyl group of alkylmagnesium compound 15 is thereby converted into an alkene 17. 

A syn-selective asymmetiic nih o-aldol reaction has been reported for structurally simple aldehydes using a new catalyst generated from 6,6-bis[(tiiethylsilyl)ethynyl]BINOL (g in Scheme 3.18). The syn selectivity in the nitro-aldol reaction can be explained by steric hindrance in the bicyclic transition state as can be seen in Newman projection. In the favored h ansition state, the catalyst acts as a Lewis acid and as a Lewis base at different sites. In conbast, the nonchelation-controlled transition state affords anti product with lower ee. This stereoselective nitro-aldol reaction has been applied to simple synthesis of t/ireo-dihydrosphingosine by the reduction of the nitro-aldol product with H2 and Pd-C (Eq. 3.79). 

Figure 1. Presumed transition state for reduction of p-keto ester 21. Only one C-21 epimer is shown for clarity.

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