In situ quench

An example for synthesis of the chiral [l-keto ester 69 is illustrated in equation 64. It involves conjugate addition of the dipotassium / -keto ester 68 to vinyl sulfone 67 followed by in situ quenching with allyl bromide54. The method provides a new procedure to sevenring annulation product 70 that is a potential precursor for (l)-(-)-cytochalasin C. 

Bromopyridine 199 can be 3-lithiated with LDA, but this too appears to be a thermodynamic effect in situ quench of the first-formed mixture of organolithiums from 199 shows some 4-lithiation even with LDA (Scheme ggf-t6,2ii... 

The chromium tricarbonyl complex 429 of triphenylphosphine oxide is hthiated and silylated (in situ quench) by 360 and McsSiCl to give 430 (X = Si) in 90% yield and 73% ee (Scheme 175) °. Interestingly, the sense of asymmetric induction is reversed from the anisole result. With two equivalents of chiral base, bis-sUyl compounds 432 could be formed. 

This is about the bottom end of the next timescale - the microscopic timescale - which is associated with the rate at which organolithium nucleophiles will add to electrophiles (usually a matter of seconds at the most). Configurational stability on the microscopic timescale is studied by the Hoffmann test, or by formation of organolithiums in the presence of electrophiles (such as Me3SiCl) with which they react immediately - in situ quench conditions. 

The corresponding saturated ketone gave, under similar conditions, (—)-a-silylated ketone in 53% yield and >92% ee. A drawback of this reaction is the incompatibility of in situ quench conditions with most electrophiles. 

It has been shown that the formation of -phenylselanyl enoxysilanes, from a-phenylselanyl cyclanones, is not regioselective even by in situ quench of the enolate with chlorotrimethylsilane and despite the more acidic character of the C-H bond of the selenenylated carbon [40] (Scheme 34). 

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-... 

In situ quench with Me3SiCl affords (18, R=Me) in 83% yield and 84% ee [49,104,105]. Increasing the size of the alkoxy group leads to a slight improvement in the stereoselectivity at the expense of yield [49]. 

While aminations of pyrimidines typically exploit SnAt substitutions, direct lithiation of pyrmidine derivatives 45 with LDA or sec-BuLi, and in situ quenching with the nitroso electrophile MNP led to the formation of the new C-N bond in the products 46 <01JOC3513>. These hydroxyl amines were subsequently oxidized to aminoxyl radical spin labels. Analogous chemistry on purine nucleosides was also reported. 

Synthesis of arylboronic acids by in situ quench procedure with n-BuLi and triisopropyl borate Preparation of 3-thienylboronic acid (364) 11481... 

S. El Sheikh, H. G. Schmalz, Halogen-lithium exchange reactions under in situ-quench conditions a powerful concept for organic synthesis, Curr. Opin. Drug Discov. Dev. 2004, 7, 882. 

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

The in situ quench (ISQ) technique [47] involves premixing of a hthium amide base (usually LDA or LTMP) and the electrophile at low temperature before addition of the arene. As soon as the orf/io-lithio anion forms, it can immediately react with the electrophile. The inverse addition protocol is equally productive, that is, a mixture of the arene and the electrophile is treated with a lithium amide base. The electrophile must be either unreactive to or react nondestructively with the lithium amide base, which therefore drastically limits useful base-electrophUe combinations. This concept was introduced by Martin for cyanobenzene deprotonation-sUylation sequences [47]. Low concentrations of aryllithiums lead to increased functional group tolerance. The ISQ technique was extended to a number of electrophiles that are compatible with lithium amide bases, including TMSCl, MejSnCl, B(OiPr)j [125, 126], benzaldehyde, Mel, EtI, and Me S. ... 

Kochemba WM, Kilbey SM, Pickel DL (2012) End-group composition of poly (3-hexylthiophene)s prepared by in situ quenching of the Grignard metathesis... 

Among the ingredients of the various recipes for the generation of lithium enolates by deprotonation, lithium salts, in particular lithium chloride, enjoyed very frequent applications [1,68]. It seems that the selectivity-enhancing effect of lithium chloride in enolate-forming reactions was detected by serendipity during the in situ quench of lithium enolates by chlorotrimethylsUane present in the... 

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