A-Lithiated intermediate

Unsymmetrical diphosphines, e.g., (86) can be prepared by reaction of the in situ-generated ArLi (or ArMgBr) with Ph2PCH2CH2PCl2 (Equation (26)).188 Dendrimer-functionalized biden-tate phosphines (87), analogs to dppe, can be prepared by the reaction of a lithiated intermediate with 1,2-bis(dichlorophosphino)ethane.189... 

An asymmetric deprotonation of 51 has been reported by Rise and Yoshida to give a lithiated intermediate which reacts with benzaldehyde to give 52 with a... 

In a related procedure A -melhyl-o-loluidine can be A-lithiated, carboxylated and C-lithiated by sequential addition of n-butyllithium, CO2, and n-butyl-lithium[5]. The resulting dilithiated intermediate reacts with esters to give 1.2-disubstituted indoles. 

Finally, metalated epoxides undergo isomerization processes characteristic of traditional carbenoids (Scheme 5.2, Path C). The structure of a metalated epoxide is intermediate in nature between the structures 2a and 2b (Scheme 5.2). The existence of this intermediacy is supported by computational studies, which have shown that the a-C-O bond of oxirane elongates by -12% on a-lithiation [2], Furthermore, experimentally, the a-lithiooxycarbene 4a (Scheme 5.3) returned cydo-pentene oxide 7 among its decomposition products indeed, computational studies of singlet 4a suggest it possesses a structure in the gas phase that is intennediate in nature between an a-lithiocarbene and the lithiated epoxide 4b [3],... 

Kattenberg and coworkers54 studied the chlorination of a-lithiated sulfones with hexachloroethane. These compounds may react as nucleophiles in a nucleophilic substitution on halogen (path a, Scheme 5) or in an electron transfer reaction (path b, Scheme 5) leading to the radical anions. The absence of proof for radical intermediates (in particular, no sulfone dimers detected) is interpreted by these authors in favour of a SN substitution on X. 

Recendy, Guiver et al. reported a number of derivatives of polysulfone and poly(aryl sulfone).172 188 Polysulfones were activated either on the ortho-sulfone sites or the ortho-ether sites by direct lithiation or bromination-lithiation. The lithiated intermediates were claimed to be quantitatively converted to azides by treatment with tosyl azides. Azides are thermally and photochemically labile groups capable of being transformed readily into a number of other useful derivatives. 

The anomeric configuration is set in the reductive lithiation step, which proceeds via a radical intermediate. Hyperconjugative stabilization favors axial disposition of the intermediate radical, which after another single electron reduction leads to a configurationally stable a-alkoxylithium intermediate. Protonation thus provides the j9-anomer. The authors were unable to determine the stereoselectivity of the alkylation step, due to difficulty with isolation. However, deuterium labeling studies pointed to the intervention of an equatorially disposed a-alkoxylithium 7 (thermodynamically favored due to the reverse anomeric effect) which undergoes alkylation with retention of configuration (Eq. 2). 

An approach to dibenzothiophenes involving a benzyne intermediate has been developed, wherein the required precursor 5, which is available in three steps from 2-fluorothiophenol, underwent lithiation giving the species 6, which could thereafter be treated with various electrophiles rendering the final products 7 <06JOC6291>. 

A neat synthesis of the chiral 10,ll-dibenzo[ / thiepine 79 from the chiral precursor 78 has been described. Cyclisation of the lithiated intermediate was mediated via reaction with sulfur W.v(i mid azole) <06OBC2218>. 

Formation of the bicyclic lithiated intermediate 8 is considered to be a two-step process whereby the nitrogen atom of nitric oxide attaches to the Cl atom of propynyllithium. Addition of a second molecule of nitric oxide gives intermediate 8 that on reaction with water produces 5-methyl-l,2,3-oxatriazole 3-oxide 9 (Scheme 1). Calculated, optimized geometry and bond lengths for stmcture 9 together with calculated infrared (IR) and Raman spectra are reported <2005JOC5045>. 

Crossed aldol condensation of an anion generated a- to a ketone equivalent with o, /3-unsaturated aldehyde, dehydration and release of the ketone is an effective way of generation of dienones. Corey and Enders found that a-lithiated /V,/V-dirnethylhydrazones undergo 1,2-addition to the aldehydes and ketones to form /1-hydroxy derivatives. Sequential treatment of the intermediate with sodium periodate and methanesulphonyl chloride-triethylamine furnishes , -2,4-dienone derivative (equation 57)94. 

A-Silylaldimine condensation with the lithiated intermediate 16 (Scheme 6), after working up the reaction under acidic conditions, produced an amino alcohol that can then be dehydrated to the benzo[d]azepine system 17 (R = Ph) <00JHC1061>. 

Qudguiner s group lithiated a sym-disubstituted pyrazine, 2,6-dimethoxypyrazine (43), with lithium 2,2,6,6-tetramethylpiperidine (LTMP). The resulting lithiated intermediate was quenched with h to give 3-iodo-2,6-dimethoxypyrazine (44) and 3,5-diiodo-2,6-dimethoxypyrazine (45) [35]. Iodide 44 was then coupled with phenylacetylene to provide adduct 46. 

Acceptor-substituted allenes can be prepared from the corresponding propargyl precursors by prototropic isomerization (see Section 7.2.2). Conversely, such allenes can also be used to synthesize propargyl compounds. For example, treatment of the sulfoxides 417 with 1 equivalent of a lithiation reagent leads to the intermediates 418, which furnish propargyl sulfoxides 419 by hydrolysis (Scheme 7.55) [101]. If the electrophiles used are not protons but primary alkyl halides or carbonyl compounds, the products 420 or 421, respectively, are formed by C,C linkage. 

The addition of carbonyl compounds towards lithiated 1-siloxy-substituted allenes does not proceed in the manner described above for alkoxyallenes. Tius and co-work-ers found that treatment of 1-siloxy-substituted allene 67 with tert-butyllithium and subsequent addition of aldehydes or ketones led to the formation of ,/i-unsaturated acyl silanes 70 (Scheme 8.19) [66]. This simple and convenient method starts with the usual lithiation of allene 67 at C-l but is followed by a migration of the silyl group from oxygen to C-l, thus forming the lithium enolate 69, which finally adds to the carbonyl species. Transmetalation of the lithiated intermediate 69 to the corresponding zinc enolate provided better access to acylsilanes derived from enolizable aldehydes. For reactions of 69 with ketones, transmetalation to a magnesium species seems to afford optimal results. 

Gasking and Whitham described the one-pot preparation of 1-silylated 3,3-di-methyl-substituted allenyl sulfides 307 (Scheme 8.82) [170]. Treatment of alkyne 305 with lithium thiolate generates allenyllithium species 306, which is subsequently silylated by trimethylsilyl chloride. Formation of lithiated intermediate 306 is based on a procedure developed by Clinet and Julia [171]. 

Various effective synthetic routes can be based on metallation of organic substrates with lithium arenes, obtained in situ from metallic lithium and an arene present in substoichio-metric amounts. Immediate quenching of the lithiated intermediates may be considered as a reduction reaction of the original substrate. Otherwise, further functionalization may be attained when using diverse electrophiles. Various examples of such processes follow (see also equation 69 in section VI.B.l). 

C-lithiated intermediates isomerize through ring-opening if not being trapped in situ stabilized by an a-triaUcylsilyl- or a-triarylsilyl substituent (as in 10, equation 6) °° ... 

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