The Origin of Stereoselection

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. 

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 ... 

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. 

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... 

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. 

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. 

A. Stimac and J. Kobe, Studies on the origin of stereoselectivity in the synthesis of, 2-trans glycofuranosyl azides, Carbohydr. Res., 324 (2000) 149-160. 

Nucleophilic substitution reactions of acetates 88 and 90 (Fig. 4.32) indicate that a single substituent at C2 is not the origin of stereoselectivity for acetal 83 (Fig. 4.32). Treatment of the trans acetate 88 with aUyltrimethylsilane in the presence of SnBr4 provided the 1,4-c/s product 89 with 67 33 stereoselectivity (Fig. 4.32). Use of BF30Et2 and Me3SiOTf as the Lewis acid provided similar selectivities. The reaction of the related cis acetate 90 also afforded a mixture of diastereoisomers. Low selectivity with C2 and C4-c/s-substituted five-membered ring oxocarbenium ions has been observed [108]. 

The Houk-List model was also applied to explain the origin of stereoselectivity in proline-catalyzed intermolecular aldol reactions [19c, 24]. Contrary to the Hajos-Parrish reaction, there is no restriction on the approach of the electrophile. Interestingly enough, theoretical calculations strongly favour an anti proline enamine... 

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