Computational studies stereoselectivity

A DFT study found a corresponding TS to be the lowest energy.167 This study also points to the importance of the solvent, DMSO, in stabilizing the charge buildup that occurs. A further computational study analyzed the stereoselectivity of the proline-catalyzed aldol addition reactions of cyclohexanone with acetaldehyde, isobu-tyraldehyde, and benzaldehyde on the basis of a similar TS.168 Another study, which explored the role of proline in intramolecular aldol reactions, is discussed in the next section.169... 

The reaction shows a dependence on the E- or Z-stereochemistry of the enolate. Z-enolates favor anti adducts and E-enolates favor syn adducts. These tendencies can be understood in terms of an eight-membered chelated TS.299 The enone in this TS is in an s-cis conformation. The stereochemistry is influenced by the s-cis/s-trans equilibria. Bulky R4 groups favor the s-cis con former and enhance the stereoselectivity of the reaction. A computational study on the reaction also suggested an eight-membered TS.300... 

A key observation was that the distribution of mono and dimagnesiated products was dependent upon the choice of magnesium alkyl, with dibutylmagnesium proving most effective for dimagnesiation. The stereoselectivity of the cyclozirconation step(s) has been rationalised with recourse to computational studies, the conclusion... 

Initially, it was thought that the glycosylation proceeded through the episulfonium intermediate 35. However, the measured kinetic isotope effect (KIE) of 1.17-1.20 suggests an oxocarbenium ion intermediate rather than an episulfonium ion [27], Furthermore, computational studies also indicated that the 3E oxocarbenium ion 36 is considerably more stable than the strained episulfonium ion 35. The observed stereoselectivity was explained by an inside attack on the 3E oxocarbenium ion. 

In the following four chapters, readers will find some of the most frequently cited and most synthetically relevant examples of the Zimmerman-Traxler or six-membered transition state. In presenting reactions that go through a six-membered chairlike transition state, I pay special attention to including computational studies, in an effort to prove the existence of a six-membered chairlike transition state. Although not all six-membered transition states have been studied computationally, recent interest in using computers in studies of stereoselective reactions would certainly confirm the legitimacy of Zimmerman-Traxler transition states for many more reactions.5... 

Bernard , A., Capelli, A. M., Comotti, A., Gennari, C., Gardner, M., Goodman, J. M., Paterson, I. Origins of stereoselectivity in chiral boron enolate aldol reactions a computational study using transition state modeling. Tetrahedron 1991, 47, 3471-3484. 

Margetic, D., Johnston, M. R., Warrener, R. N. High-level computational study of the site-, facial-and stereoselectivities for the Diels-Alder reaction between o-benzoquinone and norbornadiene. Molecules [online computer file] 2000, 5,1417-1428. 

Computational studies designed to rationalize the observed sense of stereoselectivity revealed that the chalcone is linked to the 9-0 H group of the catalyst by hydrogen bonding. The aromatic Jt-Jt interactions between the quinoline ring of catalyst 56a and chalcone further stabilize the transition-state structure and direct the FBSM to approach from the Re-face of the chalcone, affording the R-isomer of 59. The Si-face is blocked by the bulky parts of the benzyl substituent of the catalyst (Figure 9.3). 

The Horner-Wadsworth-Emmons modification of the Wittig reaction continues to find wide application in contemporary organic synthesis. Two reviews, looking at different aspects of the stereoselectivity of this procedure, have been published. One considers approaches to improve the Z-selectivity of the Horner-Wadsworth-Emmons reaction, and the other the use of heteroatoms to improve the stereoselectivity of the Horner-Wadsworth-Emmons reaction. A combined experimental and computational study of the selectivity of the Horner-Wadsworth-Emmons reaction of a series of phosphonoacetates (172) has... 

Addition of SO2 to the allenes 15 has been demonstrated to give the thiophene derivatives 16. The regio- and stereoselectivity of these reactions was corroborated by a computational study <05OL1565>. The formation of tetrahydrothiophene 1,1-dioxides has also been observed during radical annulations using SO2 as a radical acceptor/donor <05JOC10854>. 

This chapter will examine structure correlations pertinent to carbonyl substitution-elimination reactions as well as results of computational studies of potential energy surfaces and transition-state structures for such reactions. We shall then assess the current standing of the original postulates as well as that of the derivative models employed in the discussion of stereoselection and regioselectivity. 

The [t 4j + t 2j] cycloaddition of alkenes and dienes is a very useful method for forming substituted cyclohexenes. This reaction is known as the Diels-Alder (abbreviated D-A in this chapter) reaction. The transition structure for a concerted reaction requires that the diene adopt the s-cis conformation. The diene and substituted alkene (called the dienophile) approach each other in approximately parallel planes. This reaction has been the object of extensive mechanistic and computational study, as well as synthetic application. For most systems, the reactivity pattern, regioselectivity, and stereoselectivity are consistent with a concerted process. In particular, the reaction is a stereospecific syn (suprafacial) addition with respect to both the alkene and the diene. This stereospecificity has been demonstrated with many substituted dienes and alkenes and also holds for the simplest possible example of the reaction, ethene with butadiene, as demonstrated by isotopic labeling. ... 

The expanding application of computational chemistry is reflected by amplified discussion of this area, especially density function theory (DFT) calculations in Chapter 1. Examples of computational studies are included in subsequent chapters that deal with specific structures, reactions and properties. Chapter 2 discusses the principles of both configuration and conformation, which were previously treated in two separate chapters. The current emphasis on enantioselectivity, including development of many enantioselective catalysts, prompted the expansion of the section on stereoselective reactions to include examples of enantioselective reactions. Chapter 3, which covers the application of thermodynamics and kinetics to organic chemistry, has been reorganized to place emphasis on structural effects on stability and reactivity. This chapter lays the groundwork for later chapters by considering stability effects on carbocations, carbanions, radicals, and carbonyl compounds. 

We have also abstracted information from several published computational studies to present three-dimensional images of reactants, intermediates, transition structures, and products. This material, including exercises, is available at the publishers web site, and students who want to see how the output of computations can be applied may want to study it. The visual images may help toward an appreciation of some of the subtle effects observed in enantioselective and other stereoselective reactions. As in previous editions, each chapter has a number of problems drawn from the literature. A new feature is solutions to these problems, which are also provided at the publisher s website at springer.com/carey-sundberg... 

Experimental findings and a computational study supported a non-covalent general acid/base activation of the reagents in the epoxidation mediated by diaiyl prolinols, where the oxa-Michael addition of the nucleophilic peroxide is the rate- and stereoselectivity determining-step, followed by a fast ring-closure step to the epoxide. The most stable transition... 

Computational studies [191] of both half-sandwich and simple hydrocarbyl yttrium complexes have led to a stereocontrol mechanism that well explains the observed high stereoselectivity of MMBL polymerization by the current catalysts. Concisely, in the proposed monometallic propagation mechanism, formation of an isotactic polymer originates chiefly from interactions between the methyl groups on... 

Houk, Rovis, and their co-workers later extended the scope of the asymmetric intermolecular Stetter reaction of p-nitrostyrenes to unactivated aliphatic aldehydes, which have rarely been utilized in this reaction due to their relatively lower electrophilicity compared with aryl aldehydes. Comparing to known scaffolds, tert-leucine derived trans-fluorinated catalyst leads to improved reactivity and enantioselectivity in this transformation. Computational studies show that the optimized catalyst is the most stereoselective one because the Re-face attack is stabilized by favorable electrostatic interactions between the phenyl group and the fluorine on the catalyst backbone (Scheme 7.31). 

Acylhydrazones, R CH=N-NHCOR , undergo stereoselective Mannich reactions with silyl ketene acetals to give j8-hydrazido esters, using activation by a chiral silicon Lewis acid. Alternatively, the use of silyl ketene imine gives a /3-hydrazido nitrile. Enantioselective (5)-l-amino-2-methoxymethylpyrrolidine (SAMP) hydrazone alkylation of aldehydes and ketones is the subject of a computational study, providing a useful screening method for possible new candidates. " ... 

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