Origin of stereoselectivity

The origin of stereoselection in 1,3-dipolar cycloadditions to chiral alkenes 97G167. 

Coupling to both termini of the 2-methyl-2-propcnyl residue occurs when the complex 5, formed from the iodo compound 4 and stiver tetratluoroborate, is allowed to react with an excess of aldehyde, giving rise to diastcreomerically pure 4-fluoro-2,4,6-trisubstituted tetrahy-dropyrans 617. The details of the reaction and, as well, the origin of stereoselectivity is unclear at present. It would not be surprising if the reaction is restricted to those aldehydes leading in the first step to homoallylic alcohols capable of forming mesomerically highly stabilized carb-enium ions on solvolysis. 

A necessary (but not sufficient) prerequisite for models of stereospecific catalytic systems is the stereoselectivity of each monomer insertion step. The possible origin of stereoselectivity for models of several kinds of catalytic systems has been investigated through molecular modeling. 

In the area of stereoselective processes, it is worth mentioning Reaction (7.18) starting from acyclic precursor 13, where the origin of stereoselectivity could be found on the transiency of radicals and their ability of reacting before racemi-zation or conformational changes. This principle is based on the knowledge of lifetime and reactivity of radicals and is called stereoselection at the steady state [29]. 

With regard to the origin of stereoselectivity in these reactions catalyzed by Rh/ (X)-binap, the stereo-determining step is the insertion of an enone to the carbon-rhodium species coordinated with (5)-binap. As shown in Eq. (3.10), for example, 2-cyclohexen-l-one should approach from its Isi face to avoid the steric hindrance of the phenyl groups of the ligand, leading to the 1,4-adduct in (5) configuration, which is consistent with the observed stereochemical outcome ... 

Figure 4.2 Origin of stereoselectivity of cinchona-derived quaternary ammonium salts.

Scheme 7. Model of origin of stereoselectivity in Pd(ll)-catalyzed kinetic resolution [17,18].

Natta postulated that for the stereospecific polymerization of propylene with Ziegler-Natta catalysts, chiral active sites are necessary he was not able to verify this hypothesis. However, the metallocene catalysts now provide evidence that chiral centers are the key to isotacticity. On the basis of the Cossee-Arlman mechanism, Pino et al. (164,165) proposed a model to explain the origin of stereoselectivity The metallocene forces the polymer chain into a particular arrangement, which in turn determines the stereochemistry of the approaching monomer. This model is supported by experimental observations of metallocene-catalyzed oligomerization. 

A recent study provides comments on the mechanism and origin of stereoselectivity in the Lewis acid catalyzed [2+2] cycloaddition reaction between ketenes and aldehydes to give P-lactones. The observations made in this study highlight the broad range of factors which must be pondered in order to understand and control stereoselectivity in a multistep reaction <02AG(E)1572>. 

Bahmanyar S, Houk KN (2001a) The origin of stereoselectivity in proline-catalyzed intramolecular aldol reactions. J Am Chem Soc 123 12911-12912 Bahmanyar S, Houk KN (2001b) Transition states of amine-catalyzed aldol reactions involving enamine intermediates theoretical studies of mechanism, reactivity, and stereoselectivity. J Am Chem Soc 123 11273-11283 Bahmanyar S, HoukKN, Martin HJ, ListB (2003) Quantum mechanical predictions of the stereoselectivities of proline-catalyzed asymmetric intermolec-ular aldol reactions. J Am Chem Soc 125 2475-2479 Barbas CF 3rd, Heine A, Zhong G, Hoffmann T, Gramatikova S, Bjoernstedt R, List B, Anderson J, Stura EA, Wilson I, Lemer RA (1997) Immune versus natural selection antibody aldolases with enzymic rates but broader scope. Science 278 2085-2092... 

A detailed study of the mechanism and origin of stereoselectivity in reactions of allyltrimethylsilane with dioxane acetals has been published. ... 

Cannizzaro CE, Ashley JA, Janda KD, Houk KN. Experimental determination of the absolute enantioselectivity of an antibody-catalyzed Diels-Alder reaction and theoretical explo- 110. rations of the origins of stereoselectivity. J. Am. Chem. Soc. 2003 125(9) 2489-2506. 

This seemingly simple result may have far reaching consequences. For example, it may help to explain the effect of added lithium salts in nucleophilic additions to cyclohexanones as discussed earlier in this chapter. Thus, model (63) shown in Figure 472.135-137 explain the enhancement of rate and may also be relevant to the origins of stereoselectivity in this reaction. Of course, the exact location of the lithium atom and the aggregation state of the adding nucleophile are subject to speculation, since for lithium these parameters seem to be highly variable. 

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. 

Lindvall, M. K., Koskinen, A. M. P. Origins of Stereoselectivity in the Corey-Chaykovsky Reaction. Insights from Quantum Chemistry. J. 

Cannizzaro, C. E., Ashley, J. A., Janda, K. D., Houk, K. N. Experimental Determination of the Absolute Enantioselectivity of an Antibody-Catalyzed Diels-Alder Reaction and Theoretical Explorations of the Origins of Stereoselectivity. J. Am. Chem. Soc. 2003,125, 2489-2506. 

Rogic, M. M., Ramachandran, P. V., Zinnen, H., Brown, L. D., Zheng, M. The origins of stereoselectivity in asymmetric reductions with boranes based on (+)-a-pinene. II. The geometries of competing transition-states and the nature of the reaction. A semiempirical study. 

K.N. Houk, J. Liu, N.C. DeMello, K.R. Condroski, Transition States of Epoxidations Diradical Character, Spiro Geometries, Transition State Flexibility, and the Origins of Stereoselectivity, ]. Am. Chem. Soc. 119 (1997) 10147. 

When multistep reactions take place, stereoselection may or may not occur at the rate-determining step. Therefore, a careful analysis of the reaction mechanism is mandatoiy if the origin of stereoselection is to be understood. 

---