Dimethyl lithiated carbons

Carbon-13 shift of common non-aromatic heterocycles with endo- and exocyclic double bonds are reviewed in Table 4.66 [416-432], - Deshieldings of / -carbons induced by carbonyl groups in heterocyclic a, /1-enones due to (—)-M electron withdrawal (e.g. 2-pyrones, coumarins) and shieldings of [ carbons in cyclic enol ethers arising from (+ )-M electron release (e.g. 2,3-dihydrofuran and oxepine derivatives in Table 4.66) fully correspond to the effects described for the open-chain analogs. Outstandingly large shift values are observed for the lithiated carbon in cyclic a-lithium enol ethers (Table 4.66). In terms of its a and / carbon-13 shifts, 2,7-dimethyloxepine is also a typical enol ether [420], Further, 2,6-dimethyl-4-pyrone [421] and flavone [422] display similiar shift values for the a, /1-enone substructure. 

Lithiation can be influenced by a range of iV-substituents. One of the most useful processes involves the iV-lithiation, carbonation, and C-2 lithiation of indoles, which leads especially to 2-haloindoles in excellent yields <92JOC2495>. C-2 Lithiation is also promoted by the 7V-dimethyl-... 

Directed lithiation of aromatic compounds is a reaction of broad scope and considerable synthetic utility. The metalation of arenesulfonyl systems was first observed by Gilman and Webb and by Truce and Amos who reported that diphenyl sulfone is easily metalated at an orf/io-position by butyllithium. Subsequently, in 1958, Truce and coworkers discovered that metalation of mesityl phenyl sulfone (110) occurred entirely at an orf/io-methyl group and not at a ring carbon, as expected. Furthermore, refluxing an ether solution of the lithiated species resulted in a novel and unusual variation of the Smiles rearrangement and formation of 2-benzyl-4,6-dimethyl-benzenesulfinic acid (111) in almost quatitative yield (equation 78). Several other o-methyl diaryl sulfones have also been shown to rearrange to o-benzylbenzenesulfinic acids when heated in ether solution with... 

Introduction of trimethylsilyl substituents attached directly to the ot-carbon atom of a-(benzotriazol-l-yl)alkyl thioethers provide new opportunities. Thus, treatment of lithiated monosubstituted a-(benzotriazol-l-yl)alkyl thioethers with chlorotrimethylsilane produces a-(trimethylsilyl)alkyl thioethers 837. In reactions with hexamethyl-disilathiane and cobalt dichloride, thioethers 837 are converted to thioacylsilanes 838 that can be trapped in a Diels-Alder reaction with 2,3-dimethylbutadiene to form 2-alkyl-4,5-dimethyl-2-trimethylsilyl-3,6-dihydro-27/-thiopyrans 839 (Scheme 133) <2000JOC9206>. 

Like most aryl halides, furyl halides and furyl triflates have been coupled with a variety of organostannanes including alkenyl, aryl, and heteroaryl stannanes in the presence of catalytic palladium. Carbamoylstannane 66 was prepared by treating lithiated piperidine with carbon monoxide and tributyltin chloride sequentially. The Stille reaction of 66 and 3-bromofuran then gave rise to amide 67 [61]. In another example, lithiation of 4,4-dimethyl-2-oxazoline followed by quenching with MesSnCl resulted in 2-(tributylstannyl)-4,4-dimethyl-2-oxazoline (68) in 70-80% yield [62], Subsequent Stille reaction of 68 with 3-bromofuran afforded 2-(3 -furyl)-4,4-dimethyl-2-oxazoline (69). 

A one-pot synthesis of the conjugated ketenedithioacetals (7) and (8) involving indirect lithiation of propene or isobutene via the potassio deriviative reaction with carbon disulfide and 5,5-dimethylation has been reported [68]. It illustrates some aspects of the reaction of organometallics with CS2. 

The lithiated species 120, also obtainable by metal exchange of the tin analogues, reacts with electrophiles such as methyl halides, benzaldehyde, or dimethyl carbonate to give products such as 123-125, respectively. ... 

The X-ray crystal structures of lithiated sulfoximines were reported in 1986/87 by Gais. Lithiated (S)-lV,S-dimethyl-S-phenylsulfoximine crystallized as its tetra-methylethylenediamine (tmeda) complex as a chiral tetramer of structure [(S)-N-methyl-5-phenylsulfonimidoyl)methyllithium]4-2(tmeda) with approximately C2 symmetry.41 Two of the lithium cations of the tetramer were coordinated to a tmeda molecule and the O atoms of two different carbanionic species. The other two lithium cations were found to be coordinated to the N atoms of three different sulfonimidoyl carbanionic species and to one C atom (the a-carbon) of each of these carbanionic species. These lithium cations were thus found to form four-mem-bered chelate rings involving the atoms, Li-Ca-S-N. A later study was successful... 

Normant and coworkers96 uses the activated amide base , also for dimethyl hydra-zone derivatives of aldehydes. In the case that these are a straight carbon chain, the a-carbon undergoes lithiation and afterwards alkylation, but when the chain is branched, a nitrile group at the a-carbon is obtained (equation 25). 

Naphthalene-catalyzed lithiation of l,3-dimethyl-2-phenylimidazolidine leads to cleavage of the benzylic carbon-nitrogen bond, with formation of an intermediate dianion. The dianion could be trapped with several electrophiles, including primary and secondary alkyl halides, as well as enolizable and nonenolizable carbonyl derivatives, affording diamines 485 in satisfactory yields (Scheme 112) <2005T3177>. 

Chiral ferrocenylphosphines were first prepared by Hayashi and Kumada in 1974 [7], The asymmetric ortho-lithiation of optically resolved iV,iV-dimethyl-l-ferrocenyl-ethylamine 1 with butyllithium reported by Ugi and coworkers [8] (see Chapter 4) was conveniently used for their preparation. The addition of diphenylchloro-phosphine to the ortho-lithiated ferrocene 2 generated from (/ )- gave R)-N,N-dimethyl-l-[(S)-2-(diphenylphosphino)ferrocenyl]ethylamine ((/ )-(S)-PPFA 3a) in 60 — 70% yield (Scheme 2-1) [9], The first R) designates the carbon central chirality... 

Planar chiral compounds should also be accessible from the chiral pool. An example (with limited stereoselectivity) of such an approach is the formation of a ferrocene derivative from a -pinene-derived cyclopentadiene (see Sect. 4.3.1.3 [81]). A Cj-symmetric binuclear compound (although not strictly from the chiral pool, but obtained by resolution) has also been mentioned [86]. Another possibility should be to use the central chiral tertiary amines derived from menthone or pinene (see Sect. 4.3.1.3 [75, 76]) as starting materials for the lithiation reaction. In these compounds, the methyl group at the chiral carbon of iV,iV-dimethyl-l-ferrocenyl-ethylamine is replaced by bulky terpene moieties, e.g., the menthane system (Fig. 4-2 le). It was expected that the increase in steric bulk would also increase the enantioselectivity over the 96 4 ratio, as indicated by the results with the isopropyl substituent [118]. However, the opposite was observed almost all selectivity was lost, and lithiation also occurred in the position 3 and in the other ring [134]. Obviously, there exists a limit in bulkiness, where blocking of the 2-position prevents the chelate stabilization of the lithium by the lone pair of the nitrogen. 

Although allylic sulfoxides produce allyl anions like (63) upon treatment with bases, 1-alkenyl sulfoxides afford a-lithiated derivatives with LDA (Scheme 39). /VA -Dimethyl-3-(phenylthio)-2-propenyl-amine also undergoes lithiation at the sp carbon next to sulfur. 

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