OrtAo-Lithiation

Snieckus et al. prepared the furan amide organozinc reagent 27 via ortAo-lithiation of furyl amide 25 followed by reaction of the resulting 2-lithiofuran species 26 with ZnBr,... 

A mechanism to explain exclusive ortAo-lithiation was first put forward by Roberts and Curtin In this mechanism, the lithiating R—Li reagent complexes first with groups like OCHj and then abstracts the ortho hydrogen, through its basic end, to generate the aromatic carbanion. A lithium atom is then introduced at this place. 

Heating benzophenones with chlorosulfonyl isocyanate affords 3-aryl-l,2-benzisothiazole 1,1-dioxides (271) <89SC417>, which are also synthesized by a one-pot reaction from ortAo-lithiated IV.IV-diphenyl nzenesulfonamides (272) with aromatic nitriles (ArCN) <89S394>. 

Scheme 3.18 Directirai of asymmetric ortAo-lithiation can be completely reversed by the choice of a suitable achiral ligand...

Whether deprotonation always occurs initially at C2 in pyridyl systems (and rearrangement to a more stable C4 organometallic then occurs) is not certain, but in general, 3-substituted pyridyl variants undergo regioselective ortAo-lithiation, with C4 substitution being the typical outcome. 

Sulphides are weak orthodirectors (Scheme 42), and the lithiation of thioanisole 89 with BuLi leads to a mixture of a- and ortholithiated compounds 90 and 91 ". The ortholithiated compound forms about one third of the kinetic product mixture, but slow isomerization to the a-lithiated sulphide follows. The isomerization is much faster (and therefore the yield of a-lithiated sulphide much higher) if BuLi is used in the presence of DABCO". With two equivalents of BuLi, clean ortho - -a double lithiation occurs, giving 92 the SCH2Li group is itself an ortAo-director" , though a weaker one than... 

A new method was found to prepare 2,3,4,4a-tetrahydro-l,2,3-benzotriazines following the rare C-C-N-N-N-C mode (a). The azo link in l-(2,6-dimethylphenyl)-3,3-di(primary alkyl)triazenes activates the a-methylene groups at N-3 sufficiently to undergo lithiation and, at the same time, most likely complexes the Li-atom brought in by metalation with BuLi. The carbanionic carbon in turn attacks a phenyl carbon atom ortAo to N-1, which is novel, since otherwise functionalized carbon atoms such as CN or a carbonyl group at C-2 are attacked (Equation (102) Section 9.01.9). No predictions regarding a wider applicability, though, are possible at present. 

Specific lithiations are not just limited to aromatic systems with electron-withdrawing groups, but also occur with electron donors attached to the benzene ring. The methoxymethoxy-group is a particularly effective group in this context, and one report this year describes lithiations in the mcta-substituted methoxy-methoxyarenes (5). It appears that the reaction conditions have a profound effect upon which ortAo-position (2- or 4-) is lithiated. Thus, if R is a weak directing... 

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