4-chloro-3-lithio

The generation of 1,2-dUithioalkanes by a double chlorine-lithio exchange is not possible, because after the first lithiation the chloro-lithio intermediate suffers spontaneously -elimination, even at temperatures as low as — 100°C3°3. However, when one of the two chlorine atoms is attached to a sp -hybridized carbon atom, as... 

Synthetic procedures are available for the preparation of fluoro, chloro, bromo and iodo compounds from the corresponding lithio derivatives. Perchloryl fluoride (FCIO3), N-chlorosuccinimide, bromine and iodine are examples of reagents which can be used to introduce fluorine, chlorine, bromine and iodine, respectively. 

Benzo[h]selenophene, 3-bromo-2-lithio-synthesis, 4, 956 Benzo[h]selenophene, 3-chloro-synthesis, 4, 116... 

Cadmium carbonate, 82 Carbodemetallation, 11 Carbometallation, 10 Carboxylic acids, 60,86 Ccrium(ni) chloride heptahydrate, 64 a-Chiral aldehyde, 112 Chiral lanthanide, 112 ff Chloro-a-lithio-a-trimethylsilanes, 21 2 Chloro-2-methylbutane, 135 4-Chloro-2-trimethylsilylamsole. 40... 

Vinylsilanes (Chapter 3) can be readily converted into a/3-epoxysilanes, normally by treatment with mcpba (/). Alternatively, a-chloro-a-lithio-a-trimethylsilanes react efficiently with aldehydes and ketones in a manner reminiscent of the Darzens reaction (2). 

Dichloroquinoxalme (191) and isopropyl 2-lithio-2-methoxy-2-( 1-methoxy-l-methylethoxy)acetate (192) (prepared in situ) gave the mixed ketal intermediate (194) that underwent gentle acid hydrolysis to afford 2-chloro-3-propoxyoxaloquinoxaline (193) [THF-(Me2NO)3PO, —78°C 20°C then 2M HCl, 25°C, 20 min 90%]. ... 

The reaction of silylborane with 1-halo-l-lithio-l-alkenes yields 1-boryl-l-silyl-l-alkenes via borate formation followed by 1,2-migration of silyl group (Equation (90)).76,240 The mechanism seems to be closely related to that proposed for the silaboration of isocyanide (Figure 2). Vinyl-substituted carbenoids, l-chloro-l-lithio-2-alkenes, react with silylpinacolborane to give l-boryl-l-silyl-2-alkanes in good yield (Equation (91)).241 This methodology is applied to the synthesis of l-boryl-l-silyl-2-cyclobutene.2 2 Similar reactions are carried out with other carbenoid... 

The intramolecular carbolithiation of 6-lithio-l-hexene (9) was studied after lithiation of 6-chloro-l-hexene (8) in the presence of a catalytic amount of DTBB (5%). At —78 °C the corresponding organolithium compound 9 is stable, giving the expected products 10 by reaction with different electrophiles. However, when the lithiation step was carried out at — 30 °C a cyclization reaction took place, so that a new organolithium intermediate 11 was formed, which reacted with the same electrophiles to give cyclic products 12 (Scheme 5). ... 

The hthiation of the to-chloro acetal 230 using a catalytic amount of naphthalene (4%) in THF at —78°C gave the corresponding masked tu-lithio enolate 231, which reacted with different electrophiles at —78 °C to room temperature yielding, after hydrolysis with water, the expected functionalized acetals 232 (Scheme 78) . 

Bromo substituents in the 6- and 6 -positions of 2,2 -bipyridines are particularly reactive, being readily converted to amino,cyano, ° al-koxyl, hydrazino, chloro, and hydrogen groups and by way of the corresponding lithio derivatives to carboxyl, methyl, aldehyde or alkylcarbonyl, and other groupings. 6,6 -Dibromo-2,2 -bi-pyridine also reacts with the disodium derivatives of polyethylene glycols to give crown ethers akin to 100, and 6,6 -bis(chloromethyl)-2,2 -bi-pyridine " and the derived 6,6 -bis(mercaptomethyl)-2,2 -bipyridine... 

Directed ort o-metalations are also applied to quinoxalines possessing 2-chloro, 2-methoxy, and pivaloylamino substituents <1993JHC1491>, but successful syntheses via the lithio intermediates are far fewer compared to pyrazines. In fact, no example of metalation on aromatic carbons can be found in the literature since 1994. However, lithiation on benzene carbons of 6-chloro-2,3-dimethoxyquinoxaline was reported <1999T5389>. 

This section describes further developments to May, 2007. A new topic relevant to thermodynamic aspects (Section 8.03.4.1) is solubility of pyrazine and its derivatives in supercritical carbon dioxide <2006CED2056>. A notable example of nucleophilic displacement of substituents (Section 8.03.5.4.2) is represented by highly selective monosubstitution of chloro substituent in 2,3-dichloropyrazine, which is converted by treatment with a-lithio ketones into a-(3-chloropyrazin-2-yl) ketones <2006T9919>. Similarly a-(chloropyrazinyl) acetic ester or acetonitrile derivatives are synthesized by using a-lithio acetic esters or acetonitriles, respectively. 

Conversely, inversion was observed during stannylation of the a-lithio compound with chloro-trimethylstannane. This provides the (S)-enantiomer of the chiral a-lithio compound, from the same precursor, by a stannylation destannylation sequence5. 

The reaction of 113 with several Af-lithioamines was investigated and the results are summarized in Table 5. Af-Methylaniline, p-chloro-Af-methylaniline and Af-benzyl-p-anisidine gave 60-67% yield of the desired Af-cyclopropyl arylamines. Diphenylamine gave the desired product however, the yield was not satisfactory. Interestingly, dibenzy-lamine did not afford the desired product at all. This result indicated that the magnesium cyclopropylidene (113) only reacts with Af-lithio arylamines. The reaction of 113 with Af-lithio nitrogen-containing heterocyclic compounds was also studied. From the results shown in Table 5, the yields of the reaction are variable as a function of the heterocyclic compounds used. 

Chloro-3-iodo-4-lithio-6-trifluoro-methyl- EI0b2, 232 (H -. Li)... 

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