Lithiation-borylation reactions

Althaus, M. Mahmood, A. Suarez, J. R. Thomas, S. R Aggarwal, V. K. Application of the Lithiation-Borylation Reaction to the Preparation of Enantioenriched Allylic Boron Reagents and Subsequent In Situ Conversion into 1,2,4-Trisubstituted Homoallylic Alcohols with Complete Control over All Elements of Stereochemistry. /. Am. Chem. Soc. 2010,132,4025-4028. 

Buchwald and co-authors reported synthesis of biaryls by a lithiation/ borylation/Suzuki-Miyaura cross coupling sequence in continuous flow [53]. Aryl bromides could be lithiated at room temperature with 2 s-10 min residence time by mixing with n-BuLi, which then reacted with B(OiPr)3 at room temperature with 1 min residence time to afford aryl borates, ArB(OiPr)3Li. The reactor was sonicated to avoid blocking by precipitated ArB(OiPr)3Li. The reaction mixture was then mixed with Pd catalyst/THF solution and reacted at 60 °C (4—10 min residence time) to give biaryls in good yields. For example, 2-fluoro-4 -methoxy-[l,l -biphenyl]-4-carbonitrile was obtained in 94% yield (4 min residence time) (Scheme 5.38). 

However, in contrast to benzene, ferrocene is sensitive to oxidation, and the ferrocenium cation, FeCpj, a paramagnetic 17-electron species, is readily formed in the presence of various oxidants. The ferrocenium cation is reluctant to undergo electrophilic substitution, and therefore reactions such as halogenation and nitration, which are important routes to substituted benzene derivatives, cannot be used for the synthesis of substituted ferrocenes. Only electrophilic substitution under nonoxidizing conditions (e.g., Friedel-Crafts acylation, Mannich reaction, borylation, lithiation or mercuration), and radical substitution are available as an entry into the chemistry of substituted ferrocenes. 

Scheme 5-3. Useful intermediates for the synthesis of ferrocene derivatives containing heteroatoms (a) Lithiation (generally with nBuLi) (b) mercuration with Hg(OAc)2, followed by reaction with LiCl or KCl (c) borylation with B(OnBu)3, followed by hydrolysis (d) CUCI2 (e) CuBr2 (f) compounds containing reactive bromo substituents, e.g., BrCX2 -CX2Br (X = F, Cl) or tosyl bromide (g) A-bromo succinimide (h) I2 (i) Br2.

The reaction of BH3 with 3,3 -diaminodipropylamine produced (27) whereas tris(dimethylamino)borane reacted with the same amine to produce (28). The synthesis of boryl cyclotrisilazanes from the reaction of chlorodiorganyl-boranes and lithiated cyclotrisilazanes has been published. ... 

Furthermore, Vedso and Begtrup have demonstrated that ortho-lithiation, in situ borylation using lithium 2,2,6,6-tetramethylpiperidide (LTMP) in combination with triisopropylborate, is highly efficient and represents an experimentally straightforward preparation of ortho-substituted arylboronic esters such as 3 [4]. The mild reaction conditions allow the presence of functionalities such as ester or cyano groups or halogen substituents that are usually not compatible with the conditions used in directed metallation of arenes (Scheme 3.2). 

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