Synthesis routes lithiation

Synthesis of Lithiated Metal Oxides. The synthesis of hthiated metal oxides, including LiCo02 and LiMn204, has be achieved through a wide variety of routes, although those practiced commercially use inexpensive starting materials, such as hthium carbonate, lithium hydroxide and the metal oxide. The physical and electrochemical properties of the materials may be controlled by the choice of starting materials and the preparation conditions. ... 

Malayamycin A has been synthesised by a lengthy route, starting with the reaction of a protected ribonolactone with a lithiated pyrimidine <06T5201>. A much shorter synthesis of the fused quinazoline asperlicin D involved direct cyclisation of a diamide <06TL693>. 

The lithiated species 15 and 16 represent highly valuable intermediates in the synthesis of novel metallasilsesquioxanes. For this purpose it is not essential to isolate these lithium derivatives as crystalline solids. It has been found a convenient synthetic route to prepare 15 in situ by metalation of 3 with three equivalents of LiN(SiMe3)2... 

Eaton and co-workers also reported the synthesis of 1,3,5-trinitrocubane and 1,3,5,7-tetranitrocubane (39) ° The required tri- and tetra-substituted cubane precursors were initially prepared via stepwise substitution of the cubane core using amide functionality to permit ort/jo-lithiation of adjacent positions. The synthesis of precursors like cubane-1,3,5,7-tetracarboxylic acid was long and inefficient by this method and required the synthesis of toxic organomercury intermediates. Bashir-Hashemi reported an ingenious route to cubane-1,3,5,7-tetracarboxylic acid chloride (35) involving photochemical chlorocarbonylation of cubane carboxylic acid chloride (34) with a mercury lamp and excess oxalyl chloride. Under optimum conditions this reaction is reported to give a 70 8 22 isomeric mixture of 35 36 37... 

These reactions have been used in the synthesis of aikaioids such as corydalic acid methyi ester 502 (Scheme i95). Isoiated from Corydalis incisa, 502 is derived from a proposed biosynthetic intermediate in the route to the tetrahydroprotoberberine aikaioids. The 1,2,3,4-tetrasubstituted ring of 502 demands control by an ortholithiation strategy, and the synthetic route proposed by Clark and Jahangir employs a lateral lithiation of 503 and addition to an imine as the key disconnection at the centre of the molecule. 

The regiospecific synthesis of substituted azine derivatives by the use of heteroatom directed lithiation has also become a common occurrence in recent years, and this route has led to the successful synthesis of a wide variety of substituted derivatives [87MI1 88AHC(44)199 90CRV879 91AHC(52)187]. The activation and stabilization provided by the heteroatom substituent mean that deprotonation can occur at lower temperatures, and thus the problem of addition to the azomethine double bond is minimized. The utility of this method, and of the different substituent groups involved in the directed metalation process, is detailed in the following sections. 

The metalation chemistry of the imidazoline system has received attention only recently, with the lithiation of l-benzyl-2-imidazoline being found to occur at the 2-position (90TL1767). Although the reactivity of the lithi-ated species with alkyl halides was poor, better results were achieved with disulfide and carbonyl electrophiles (90TL1767,90TL1771). The products formed by reaction with ketones were found to be unstable with respect to fragmentation, and this result was utilized to provide a new route for the synthesis of unsymmetric ketones (Scheme 138). 

During studies relating to the synthesis of certain trialkylsilylferrocenes from lithiated ferrocenes and trialkylchlorosilanes, Rausch and coworkers detected minute amounts of a dark orange crystalline substance which was subsequently shown to be biferrocenyl on the basis of analytical evidence (27, 92). To provide an unequivocal synthesis and a more satisfactory route to this compound, several alternative routes were investigated. 

Another preparative route for synthesis of benzisoselenazol-3(27/)-ones is based on the lithiation of the benzamides, followed by the conversion of dilithium derivatives by direct treatment with selenium, or via 2-[(carbamoyl)phenyl]methyl selenides or 2,2 -bis[(carbamoyl)phenyl] diselenides [167-172], These diselenides are oxidatively cyclized and, depending on the oxidant used, benzisoselenazol-3 (2H)-ones or their 1-oxides are produced in high yields [92, 173],... 

Thus, in 1997 Weidenbruch and coworkers have reported the synthesis and isolation of the first stable conjugated Si-Si double-bond compound, i.e. hexatipyltetrasilabuta-1,3-diene 9479. Tetrasilabutadiene 94 was prepared through a rather unique synthetic route starting from the corresponding tetraaryl-substituted disilene 95 via the mono-lithiated disilene 96 as shown in Scheme 35. 

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