Diastereoselectivity 1,4-asymmetric induction

In a similar manner to normal Alder ene type reactions, transition metals also catalyze the ene reactions of dienes with olefins36 -38,50. This type of reaction can be considered as a 1,4-addition of an alkene to a diene. Diastereoselective asymmetric induction can be achieved if the alkene unit is incorportated into a chiral acetal37. 

Diastereoselective asymmetric induction in cobalt-catalyzed cyclopropanation is also reported for the cyclopropanations of (-)-dimenthyl and (-)-dibornyl fumarates with geminal dihalides28. 

The palladium-mediated [3 + 2] cycloaddition is a stereospecific cis addition with retention of the alkene geometry. With chirally modified (E)- and (Z)-crotonates diastereoselective asymmetric induction is observed, with the Z-isomer showing a much higher diastereofacial selectivity32. A similar asymmetric induction occurs with chirally modified sulfones15. 

A catalytic enantio- and diastereoselective dihydroxylation procedure without the assistance of a directing functional group (like the allylic alcohol group in the Sharpless epox-idation) has also been developed by K.B. Sharpless (E.N. Jacobsen, 1988 H.-L. Kwong, 1990 B.M. Kim, 1990 H. Waldmann, 1992). It uses osmium tetroxide as a catalytic oxidant (as little as 20 ppm to date) and two readily available cinchona alkaloid diastereomeis, namely the 4-chlorobenzoate esters or bulky aryl ethers of dihydroquinine and dihydroquinidine (cf. p. 290% as stereosteering reagents (structures of the Os complexes see R.M. Pearlstein, 1990). The transformation lacks the high asymmetric inductions of the Sharpless epoxidation, but it is broadly applicable and insensitive to air and water. Further improvements are to be expected. 

High levels of asymmetric induction have been achieved in the hydroboration of 1,3-, 1,4-, and 1,5-dienes with thexylborane (482,483,489,490). The first chiral center is formed by an intermolecular reaction. In the second step, the organoborane intermediate undergoes an intramolecular hydroboration, creating the second chiral center with high diastereoselectivity. 

The enantiomers are obtained as a racemic mixture if no asymmetric induction becomes effective. The ratio of diastereomers depends on structural features of the reactants as well as the reaction conditions as outlined in the following. By using properly substituted preformed enolates, the diastereoselectivity of the aldol reaction can be controlled. Such enolates can show E-ot Z-configuration at the carbon-carbon double bond. With Z-enolates 9, the syn products are formed preferentially, while fi-enolates 12 lead mainly to anti products. This stereochemical outcome can be rationalized to arise from the more favored transition state 10 and 13 respectively ... 

The sense of asymmetric induction could be tuned in two ways firstly through the chirality of the sufinyl group, and secondly through the use of dimethylox-osulfonium methylide (n = 1) or of dimethylsulfonium methylide (n = 0), which was found to provide aziridines with opposite diastereoselectivity. This was interpreted by assuming the process to be under thermodynamic control in the former... 

It is interesting to speculate that asymmetric induction may be the consequence of the exo anomeric effect, a stereoelectronic effect that favors the conformation 5 that places the aglycone O-C bond antiperiplanar to the pyran C(1) —C(2) bond7fi. Related asymmetric induction has also been observed in aldehyde addition reactions of the related, but racemic, pinacol (Z)-y-(tetrahydropyranyloxy)allylboronate49. As indicated in the examples above, however, the level of diastereoselectivity is modest and the only application in asymmetric synthesis is Wuts exo-brevicomin synthesis75. 

Optically active Art-butyl 2-(4-methylphenylsulfinyl)propanoate only reacted with aldehydes in the presence of e//-butylmagnesium bromide as a base36. The asymmetric induction for the formation of the hydroxylic center was higher in the case of aliphatic aldehydes (75-80%) than in the case of benzaldehyde (33%). The diastereoselectivity regarding the tertiary center to sulfur was not determined. 

This 1,2-asymmetric induction has been attributed to stcric and stcrcoclectronic factors. Similarly, the cuprate additions to 4-alkylcyclopentenones l7 -19, and 4-alkylcyclohexcnones16 b-18 proceeded with very high trans diastereoselection. The copper iodide catalyzed addition of propylmagnesium bromide to 4-methyl-2-cyclohexenone gave a trans/cis ratio of 80 20, whereas the addition to 5-methyl-2-cyclohexenone produced a transjcis ratio of 93 72 3-Silyloxy system 3 gave the trans-adduct 4 on treatment with butylcopper-boron trifluoride reagent20. 

Substantially high diastereoselectivity was accomplished by the conjugate addition of Grignard reagents to the amide 1 derived from 1-ephedrine32. The reagent attacked from the Re-face of the double bond, as shown in 2, via a chelated intermediate. Low asymmetric induction was observed when butyllithium was used instead of butylmagnesium bromide. 

I.5.2.2.3.2.4. Asymmetric Induction from the Stereocenter on the Acceptor Combined with Simple Diastereoselection... 

This section describes Michael-analogous processes in which, mostly under electrophilic conditions, ally - or alkynylsilanes undergo addition to enones or dienones (Sakurai reactions). The intramolecular addition of allylsilanes is an extremely useful reaction especially for the construction of carbocyclic ring systems, which occurs in a diastereoselective manner, in many cases with complete asymmetric induction. 

Reactions of nitro compounds with chiral imines have only recently been described. Either chiral 1-phenylethylamine (auxiliary) or the glyceraldehyde acetonide aldehyde was used as the chiral precursors of the imines 66 and 68, which reacted with 3-mesyloxynitropropane to give the 3-nitropyrrolidines dl)-67 and 69, respectively, with good diastereoselectivity. In fact, both products were obtained (almost) exclusively as trans diastereomers with high level of asymmetric induction, but the configurations of the newly formed stereocenters were not determined [44] (Scheme 13). N-Boc imines can be formed... 

Double asymmetric induction operates when the azomethine compound is derived from a chiral a-amino aldehyde and a chiral amine, e.g., the sulfin-imine 144 [70]. In this case, the R configuration at the sulfur of the chiral auxihary, N-tert-butanesulfinamide, matched with the S configuration of the starting a-amino aldehyde, allowing complete stereocontrol to be achieved in the preparation of the diamine derivatives 145 by the addition of trifluo-romethyl anion, which was formed from trifluoromethyltrimethylsilane in the presence of tetramethylammonium fluoride (Scheme 23). The substituents at both nitrogen atoms were easily removed by routine procedures see, for example, the preparation of the free diamine 146. On the other hand, a lower diastereoselectivity (dr 80 20) was observed in one reaction carried out on the imine derived from (it)-aldehyde and (it)-sulfinamide. 

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