External quench conditions

This finding has been exploited using other ketones and chiral bases. Thus deprotonation of the bicyclic ketone 30 by chiral base 3 in THF yielded the silylenol ether 31 in 84% ee under external quench conditions with added LiCl (Scheme 22)49. In absence of LiCl the ee was lowered to 33%. Internal quench conditions gave an ee of 82%. 

In some cases, any effect of added LiCl was not noticeable in aldol reactions under external quench conditions. Majewski and coworkers have observed that aldol reaction of tropinone 32 and benzaldehyde using the chiral lithium base 26 in the presence as well as in the absence of added LiCl gave the aldol product with the same 90% ee (Scheme 24)53,56. 

Tetrahydroisoquinoline-based diamines, such as 46, have been reported by Aggarwal and coworkers. Its use in the deprotonation of 4-f-butyl cyclohexanone 28 gave low enantioselectivity, but in the presence of HMPA an ee of 81% of (S)-29 was obtained. In this case, external quench conditions gave the highest enantioselectivity (Table 2)70. 

TABLE 2. Deprotonation of 28 under internal and external quench conditions O OSiMe3 OSiMe3... 

More recently, Amedjkouh has described the use of 48 in deprotonation of 28. Silylenol ethers could be obtained with 85% and 75% ee under internal quench and external quench conditions, respectively (Scheme 32). Mixed dimers 49 and 50 (see Section II.E.2) proved to be effective under external quench conditions and provided silylenol ether in up to 63% ee73. 

Deprotonation of 4-f-butyl cyclohexanone 28 with chiral lithium amide 39 (30 mol%) and bulk base 107 (240 mol%) in the presence of HMPA (240 mol%) and DABCO (150 mol%), under external quench conditions, resulted in 79% ee of the silyl enol ether 29 (Scheme 79)121. This stereoselectivity is only slightly lower than that of the stoichiometric reaction (81% ee). 

Remarkable improvements in chiral base-mediated reactions of prochiral ketones under external quench (EQ) conditions with TMS-Cl, furnishing enantiomerically pure enol silanes, were found upon deprotonation in the presence of LiCl. [22, 24] Simpkins et al. studied for instance the conversion of 4-tert-butylcyclohexanone 9 into enol silane 10 by employing the chiral amide base 11 (Scheme 9). [24] Applying the TMS-Cl in situ quench (TMS-Cl-ISQ) protocol a higher level of enantiomeric excess was observed compared to external quench conditions (EQ). However, under external quench conditions in the presence of LiCl (EQ-i-LiCl procedure) significantly higher levels of asymme-... 

It is obvious that the difference (p — p) is closely related to the quench depth or the thermodynamic driving force while the rate of the process is determined by the viscosity. According to these factors structure evolution is ruled by both externally imposed conditions and intrinsic properties of the system. 

Under conventional external quench (EQ) conditions, the aiene and the base are premixed prior to addition of the electrophile. In general, the thermodynamic equilibrium existing between the anions intermediately formed is displaced toward the most stable (less basic) anion owing to its stabilization by the substituents (Fig. 26.7). 

The deprotonation of conformationally locked 4-t-butylcyclohexanone became a kind of benchmark reaction to study the efficiency of appropriate chiral bases. As shown in Scheme 2.20, the enantiotopic axial hydrogen atoms in o-position of the carbonyl group can be removed selectively by the C2-symmetric lithium base R,R) or (S,S)-72a, and the enantiomeric enolates R)-73a and (S)-73a thus formed were trapped with chlorotrimethylsilane to give enantiomeric silyl enol ethers (/ )-73b and (S)-73b, respectively. It turned out that - symptomatically for the chemistry of lithium enolates - the conditions have a dramatic effect on the enantioselectivity. When internal-quench conditions were applied (i.e., chlorotrimethylsilane present in the mixture from the very beginning), R)-73 was obtained in 69% ee. The external-quench protocol (i.e., deprotonation with the lithium amide 72a first, followed by trapping with chlorotrimethylsilane) led to a collapse of enantioselectivity (29% ee). Thus, here again, the idea came up that lithium chloride that forms gradually under the internal-quench conditions influences dramatically the deprotonation mode. Consequently, the enolate formation was performed in the presence of lithium chloride (0.5 equiv.), and chlorotrimethylsilane was added thereafter. The result was an enhancement of the ee value to 83% [75]. 

Generally, several protocols are used for the characterization of sohd-catalyzed reactions under batch reaction conditions by NMR spectroscopy. In ex situ experiments, the conversion of reactants adsorbed on the catalyst is carried out in an external oven and stopped after a given reaction time by quenching, for example, in liquid nitrogen. Subsequently, the reaction products formed on the catalyst surface are investigated at room temperature by use of a standard MAS NMR probe. This protocol is repeated with a stepwise increment of the reaction time at the same temperature or with a stepwise increment of the reaction temperature for the same duration. In an in situ experiment, the catalytic conversion of the reactants is measured inside the NMR spectrometer by use of a high-temperature MAS NMR probe. 

---