External quench

The results of external quenching studies using fra/u-jS-methylstyrene as a quencher are shown in Figures 6.15 and 6.16. 

Substituted cyclohexanones, bearing a methyl, isopropyl, tert-butyl or phenyl group, give, on deprotonation with various chiral lithium amides in the presence of chlorotrimethylsilane (internal quench), the corresponding chiral enol ethers with moderate to apparently high enantioselec-tivity and in good yield (see Table 2)13,14,24> 29 36,37,55. Similar enantioselectivities are obtained with the external quench " technique when deprotonation is carried out in the presence of added lithium chloride (see Table 2, entries 5, 10, and 30)593. 

The enantioselectivity of the two-step process (deprotonation and trapping of the enolate) is considerably higher in the case of internal quenching with chlorotrimethylsilane as shown by the results of the external quenching of the lithium enolate with acetic anhydride (Table 4)20. 

Deprotonation of tropinone (1) with various chiral lithium amides and external quenching of the lithium enolate with benzaldehyde gives the aldol product 2 in moderate to good yield with moderate enantiomeric excess but high diastcrcosclcctivity. The aldol product 2 is a single diastereomer with the relative configuration as depicted, but of unknown absolute configuration19. Recrystallization of the aldol product leads to enantiomerically pure material. 

Hence the quantum yield of fluorescence 4> n the absence of any external quenching is, from definition, (5.28)... 

Similarly, when, attempted tritiation of the anthryllithium 30 with T20 as an external quench failed because of competing protonation, the solution was to use T20 as an internal quench halogen-metal exchange of 29 proceeds in the presence of the T20 at -70 °C.36... 

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%. 

External quench protocols in the presence of LiCl have been extended to reactions with other electrophiles. Thus, both Simpkins and coworkers49 52 and Majewski and coworkers53-55 have investigated the aldol reaction of tropinone 32 with benzaldehyde... 

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. 

Simpkins and coworkers reported the use of chiral bases in the enantioselective generation of bridgehead enolates (Scheme 36)76. Initial studies revealed that external quench protocols were ineffective in trapping the carbanion. Addition of a mixture containing chiral base (R,R) 3 and LiCl to a solution of ketone 55 and TMSC1 at —105 °C gave mono (—)-a-silylated ketone 56 in 76% yield and >96% ee. 

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). 

Substantial improvements of the ee of another desymmetrization process are also observed in the presence of LiCl (Sch. 16). Results obtained for formation of enol silane 36 show that when a base is reacted with the ketone before MeaSiCl treatment (external quench EQ method), the ee is low (33 %). Under the external quench technique in the presence of LiCl (10 mol %), however, the ee is enhanced to 84 %, comparable with the 82 % ee obtained by an internal quench technique (IQ method addition of MeaSiCl before treatment with 35). It should be noted that unlike the E/Z ratios and ee mentioned above (Sch. 12), no subsequent drop in ee is seen when 1 equiv. or more LiCl is used. Further experiments involving the LiCl-assisted aldol reaction of tropinone 37 also resulted in increased ee [57]. 

External quenching during protonolysis of unactivated cyclopropanes is rare, since the strong acids necessary to protonate these substrates are very poor nucleophiles. Generally proton elimination from the intermediate propyl cation strongly predominates. 

However, products from external quenching are obtained in protonolyses of cyclopropanes that are activated by electron-withdrawing substituents, since in these cases weaker acids (better nucleophiles) can be used to induce the cleavage. This is astonishing and seems to indicate that the polarization of the cyclopropane bonds or the neighborhood of a protonated hetero functionality and not the electron density determines the ease of the proton attack. Examples are given by the formation of 45, 47, 50, 52, " and... 

Internal conversion Self quenching External quenching... 

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-... 

Time-of-Flight. The term is used in experiments of high-energy physics, mass spectroscopy, and diffuse optical tomography (DOT). The TOF-distribution in DOT is the distribution of the photons versus time after propagation through a turbid medium. Fluorescence lifetime spectroscopy r is used for the fluorescence lifetime or the lifetime components in multiexponential decay functions. rn=natural lifetime in the (hypothetical) absence of all nonradiative decay processes, To = observed lifetime in the absence of external quenching processes, Tmt rotational depolarisation time. 

Good protection Confirmed nona-dentate Avoid water and minimize other external quenching... 

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). 

External quench (EQ) —> Thermodynamic product In situ quench (ISQ) — Kinetic product... 

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