Henri B. Kagan

Nonlinear Effects in Asymmetric Synthesis and Stereoselective Reactions: Ten Years of Investigation

Who would have thought before 1986 that an enantiomerically impure catalyst could give a product in an asymmetric synthesis with an enantiomeric excess higher than that of the catalyst? Until then it was assumed that the ee value of the product (eeprod ) from an asymmetric synthesis was linearly correlated to the ee value of the chiral auxiliary (eeaux )-in fact a large deviation is possible (see diagram). These nonlinear effects are not only of academic interest since they have a variety of practical uses, which are highlighted in this review.

Nonlinear Effects in Asymmetric Catalysis

There is a need for the preparation of enantiomerically pure compounds for various applications. An efficient approach to achieve this goal is asymmetric catalysis. The chiral catalyst is usually prepared from a chiral auxiliary, which itself is derived from a natural product or by resolution of a racemic precursor. The use of non-enantiopure chiral auxiliaries in asymmetric catalysis seems unattractive to preparative chemists, since the anticipated enantiomeric excess (ee) of the reaction product should be proportional to the ee value of the chiral auxiliary (linearity). In fact, some deviation from linearity may arise. Such nonlinear effects can be rich in mechanistic information and can be synthetically useful (asymmetric amplification). This Review documents the advances made during the last decade in the use of nonlinear effects in the area of organometallic and organic catalysis.

Efficient formation of pinacols from aldehydes or ketones mediated by samarium diiodide

Abstract Samarium diiodide is an excellent reagent for aldehyde or ketone coupling. With aromatic aldehydes, reactions are very fast with a complete selectivity versus substituents such as cyano, carboxyl or nitro groups.

Asymmetric oxidation of sulfides mediated by chiral titanium complexes : mechanistic and synthetic aspects

Abstract Asymmetric oxidation of sulfides by hydroperoxides mediated by chiral titanium complexes was further developed.The effect of water was discussed as well as steric and electronic factors of aryl groups in aryl-S-alkyl oxidation. When aryl is replaced by 1-alkyne, the sulfoxide is still obtained with high ee. The enantioselectivity of oxidation is enhanced by using cumene hydroperoxide instead of t-butyl hydroperoxide (up to 96%). The asymmetric oxidation was also run under catalytic conditions (with respect to the titanium complex) and beneficial effects were observed in the presence of molecular sieves in the reaction medium.

Reduction asymetrique catalysee par des complexes de metaux de transition IV. synthese d'amines chirales au moyen d'un complexe de rhodium et d'isopropylidene dihydroxy-2,3 bis(diphenylphosphino)-1,4 butane (diop)☆

Abstract A chiral rhodium complex with (+)-diop as ligand is used as a catalyst in asymmetric synthesis leading to amines and N -acyl derivatives. Two kinds of reactions are investigated: asymetric hydrogenation of enamides and hydrosilylation of imines. Good optical yields are observed in the synthesis of N -acetyl α-phnenylethylamine (e.e. 45%) and N -acetyl α-phenylpropylamine (e.e. 83%). A strong solvent effect is observed, which can reverse the absolute configuration of tN -acetyl-α-phenylethylamine obtained by reduction of its enamide precursor. N -Benzyl-α-phenyl ethylamine is prepared by hydrosilylation with 65% optical purity. An asymmetric synthesis of 1,2,3,4-tetrahydropapaverine (e.e 38%) and related compounds is described.

Use of Nonfunctionalized Enamides and Enecarbamates in Asymmetric Synthesis

4. Mannich Reaction 4644 5. Self-Coupling of Enamides 4644 6. Michael Reaction 4644 7. Cyclization Reactions 4645 8. Povarov Reaction 4647 9. Hetero-Diels Alder Reaction 4648 10. Friedel Crafts Reaction 4648 11. Intramolecular Heck Reaction 4650 12. Hydroformylation 4651 13. Hydroboration 4651 14. Hydroamination 4651 15. Epoxidation of Chiral Enecarbamates 4652 16. Simmons Smith Cyclopropanation 4653 17. Photooxygenation of Chiral Enecarbamates 4653 18. Conclusion 4653 Author Information 4654 Biographies 4654 References 4654

Reduction asymetrique catalysee par des complexes de metaux de transition : III. Diphosphines chirales derivees de l'isopropylidene dihydroxy-2,3 bis(diphenylphosphino)-1,4 butane (diop)

Abstract Various chiral diphosphines related to diop, isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane, have been prepared. Substitution of a methyl group at the meta position of each aromatic ring increases optical yields, which can reach 90% (asymmetric synthesis of a 3-(3,4-dihydroxyphenyl)alanine derivative). Excellent results from asymmetric catalysis have also been obtained using structural analogues of diop in which the acetonide ring is placed by a carbon ring.

Some organic reactions promoted by samarium diiodide

Abstract Various homoallylic alcohols and homobenzylic alcohols were prepared by the reaction between aldehydes and allylic or benzylic halides in the presence of samarium diiodide. This iodide is also a very good reagent for formation of pinacols from aldehydes or ketones. The reactions are especially fast and selective in the case of substituted benzaldehydes. The reactivities of various nitrogen functional groups (imine, oxime, nitro, azo, cyano) towards SmI2 were also examined.

Asymmetric catalysis by chiral rhodium complexes in hydrogenation and hydrosilylation reactions

ABSTRACT The preparation of optically active molecules needs a chiral auxiliary. It is important to use the minimum amount of this auxiliary, and from that point of view asymmetric catalysis is much more advantageous than stoichiometric asymmetric synthesis. Some homogeneous catalysts prepared from chiral complexes have become during the past few years a useful tool in asymmetric synthesis. The complexes L2RhCl where L2 is a family of chiral diphosphines were prepared and used in asymmetric reduction. DIOP is a readily available ligand prepared from tartaric acid. Many of its derivatives were obtained as well as other types of chiral phosphines. General syntheses of optically active α-amino acids, amines or acids are described. Optical yields as high as 90 per cent could be attained. The same complexes can catalyse the hydrosilylation of ketones and imines, giving rise after hydrolysis to optically active alcohols and amines. To improve the usefulness of asymmetric catalysis a supported chiral catalyst was prepared starting from a Merrifield resin. It was used both in reduction and in hydrosilylation. The mechanism of the reactions and the origin of the asymmetric induction will be discussed.

Use of samarium diiodide in the field of asymmetric synthesis

Samarium diiodide may be a useful reagent in a step of an asymmetric synthesis process. It can release a blocking group in mild conditions, as described in several examples. SmI2 has been used as electron donor in many C–C bond formations in presence of a chiral auxiliary. It can also generate samarium enolates which were subjected to asymmetric protonation. The examples selected in this review of SmI2 methodology concern only the cases where the chiral auxiliary is not retained in the final product.