Asymmetric induction period

A more eflicient and general synthetic procedure is the Masamune reaction of aldehydes with boron enolates of chiral a-silyloxy ketones. A double asymmetric induction generates two new chiral centres with enantioselectivities > 99%. It is again explained by a chair-like six-centre transition state. The repulsive interactions of the bulky cyclohexyl group with the vinylic hydrogen and the boron ligands dictate the approach of the enolate to the aldehyde (S. Masamune, 1981 A). The fi-hydroxy-x-methyl ketones obtained are pure threo products (threo = threose- or threonine-like Fischer formula also termed syn" = planar zig-zag chain with substituents on one side), and the reaction has successfully been applied to macrolide syntheses (S. Masamune, 1981 B). Optically pure threo (= syn") 8-hydroxy-a-methyl carboxylic acids are obtained by desilylation and periodate oxidation (S. Masamune, 1981 A). Chiral 0-((S)-trans-2,5-dimethyl-l-borolanyl) ketene thioketals giving pure erythro (= anti ) diastereomers have also been developed by S. Masamune (1986). 

Herrmann et al. reported for the first time in 1996 the use of chiral NHC complexes in asymmetric hydrosilylation [12]. An achiral version of this reaction with diaminocarbene rhodium complexes was previously reported by Lappert et al. in 1984 [40]. The Rh(I) complexes 53a-b were obtained in 71-79% yield by reaction of the free chiral carbene with 0.5 equiv of [Rh(cod)Cl]2 in THF (Scheme 30). The carbene was not isolated but generated in solution by deprotonation of the corresponding imidazolium salt by sodium hydride in liquid ammonia and THF at - 33 °C. The rhodium complexes 53 are stable in air both as a solid and in solution, and their thermal stability is also remarkable. The hydrosilylation of acetophenone in the presence of 1% mol of catalyst 53b gave almost quantitative conversions and optical inductions up to 32%. These complexes are active in hydrosilylation without an induction period even at low temperatures (- 34 °C). The optical induction is clearly temperature-dependent it decreases at higher temperatures. No significant solvent dependence could be observed. In spite of moderate ee values, this first report on asymmetric hydrosilylation demonstrated the advantage of such rhodium carbene complexes in terms of stability. No dissociation of the ligand was observed in the course of the reaction. 

The hydrogen consumption and enantioselectivities for the asymmetric hydrogenation of dimethyl itaconate with various substituted catalysts of the basic type [Rh(PROPRAPHOS)COD]BF4 are illustrated in Figure 10.13 [61]. The systems are especially suitable for kinetic measurements because of the rapid hydrogenation of COD in the precatalyst. There are, in practice, no disturbances due to the occurrence of induction periods. 

Such induction periods can, for example, result from transferring a precatalyst into the active species. For the asymmetric hydrogenation this is described in detail in (a) W. Braun, A. Salzer, H.-J. Drexler, A. Spannenberg, D. Heller, Dalton Trans. 2003, 1606 (b) H.-J. Drexler, W. Baumann, A. Spannenberg, C. Fischer, D. Heller,/. Organomet. Chem. 2001, 623, 89 ... 

Mechanistic studies showed that metalacycle la is competent to be a catalyst in asymmetric allylic substitution reactions. The reaction of benzylamine with methyl ciimamyl carbonate catalyzed by a mixture of LI and [Ir(COD)Cl]2 occurs with an induction period and forms product in 84% yield and 95% ee, whereas the same reaction catalyzed by a mixture of metalacycle la and [Ir(COD)Cl]2 occurs without an induction period in just 2 hours to form the substitution product in 81% yield and 97% ee. The latter reaction was conducted with added [Ir(COD)Cl]2 to trap the -bound LI after dissociation. This ligand must dissociate to provide a site for oxidative addition of the allylic carbonate. 

The [2H-2]-cycloaddition of ketenes with imines is an excellent method for the generation of azetidinones, generally providing good yields and allowing a wide latitude in substitution pattern on the product. The major advances in this field during the period covered by this review have been in the synthesis of optically active compounds by asymmetric induction in the cycloaddition step. Chiral auxiliaries have been employed at all four positions of the azetidinone ring. 

In a continuation of his studies on asymmetric P-lactam synthesis, Evans [42] utilized a,P-epoxyaldehydes 49a and 49b, prepared in two steps from achiral allylic alcohols via Sharpless asymmetric epoxidation and Swern oxidation, as chiral glyoxal synthons for the ketene-imine cycloaddition. Diastereosel-ection was excellent, ranging from 90 10 to 97 3 with overall yield of 50 up to 84% (for Schiff base formation and cycloaddition) after recrystallization or chromatographic purification of the major diastereomer. The sense of asymmetric induction correlated with that obtained in the analogous glyceraldehyde reaction, as established by periodic acid cleavage to aldehydes 51. 

The formation of the DADB salt comes from the reaction of small, hard bases (like ammonia) with a borane species. Considering B2H6, the base induces an asymmetric cleavage of borane into a BH2 fragment, and a BHq fragment [53]. The borohydride is stable, and BH2 coordinates two bases. In the thermal decomposition of amine borane, researchers often see induction periods wherein reactions are slow to begin, and then accelerate later. These induction periods are potentially isomerization of BH3NII3 into the DADB salt, followed by further reaction [83]. 

Both nickel(0)- and nickel(n)-phosphine complexes, e.g. [Ni(C2H4)(diphos)], [NiCl2(diphos)], can catalyse hydrosilylation of alkenes. An induction period is observed with the nickel(ii) system and it appears that an important step with these catalysts is reduction of nickel(ii) to nickel(0). The reduction does not occur below 100 °C. A possible mechanism for the reaction is given in Scheme 27. Asymmetric hydrosilylation of styrene and cyclic dienes with HSiCls can... 

For the BINlM-Ni(ll)-catalyzed reactions of cyclohexyl vinyl ether, the use of an epoxyindanone as the 3-acyl-2-benzopyrylium-4-olate precursor revealed that the chiral Lewis acid can function as a catalyst for asymmetric induction (Scheme 7.29). Thus, slow addition (over a period of 1 h) of epoxyindanone into a solution of cyclohexyl vinyl ether and the Ni(ll) catalyst in dry CH2CI2 under reflux conditions gave eniio-cycloadduct (60% yield) with 86% ee. This result suggests that the asymmetric induction is effectively catalyzed by the (7 )-BINIM-4Me-2QN-Ni(II) complex, and without the participation of Rh2(OAc)4, which may be involved only in the generation of the carbonyl ylides for reactions of diazocarbonyl compounds as substrates [66]. 

---