Investigation into the mechanism of lithiation of 2,3-dihydrooxepin

The NMR characterization of the trienolate product of lithiation of 2,3-dihydrooxepin with 6-lithiodihydropyran in THF is reported. The NMR spectra also support a direct ring opening upon allylic lithiation via an E2-type mechanism rather than vinylic lithiation or stepwise allylic lithiation. We also found the structure of the trienolate product of this reaction to be the Z, Z configuration.     

First C-3 lithiation of DMAP: a new entry into chemical tuning of acylation catalysts

A TMSCH2Li-based reagent promoted the first C-3 lithiation of DMAP opening a direct access to functional diversity in acylation catalysts.     

Novel and convenient routes to substituted pyrroles and imidazoles

S-Melhyl N-(benzotriazol-1-ylmethyl)thioimidate 6 is obtained by lithiation of the corresponding N-(benzotriazol-1-ylmelhyl) thioamide 5 and subsequent reaction with methyl iodide. Derivative 6 undergoes [2 + 3] cycloaddition reactions with ,β-unsaturated -esters, -ketones and -nitriles, and vinylpyridines which are followed by elimination of benzotriazole and the thioalkoxy group, to give 2,3,4-trisubstituted pyrroles. Lithiaiion of 6 followed by reactions with imines gives cyclized 4,5-dihydroimidazoles 14 which upon further treatment with ZnBr₂ or direct refluxing in toluene yield the 1,25-trisubstituted imidazoles 15 in good yields.     

Direct lithiation and alkylation of trifluoromethyl enol ethers having a beta-sulfur substituent

The direct lithiation and alkylation of beta-sulfur-alpha-trifluoromethyl substituted enol ethers 1-3 proceeded to give the alkylated products 4a-f, 5, 6a-c in moderate to high yields.     

Synthesis, structure and reactivity of 4-phosphanylated 1,3-dialkyl-imidazole-2-thiones

Selective formation of 4-phosphanylated 1,2-dialkyl imidazole-2-thiones 3a-f has been obtained via a lithiation followed by phosphanylation reaction. The reactivity of 3a-f was examined towards oxidation and complexation reactions. All products were unambiguously characterized by elemental analyses, spectroscopic and spectrometric methods including X-ray analysis (3a, 3b, 4b, 4d, 5b, 6a and 6d).     

Formation of lithium fluoride/metal nanocomposites for energy storage through solid state reduction of metal fluorides

In order to utilize high energy metal fluoride electrode materials as direct replacement electrode materials for lithium ion batteries in the future, a methodology to prelithiate the cathode or anode must be developed. Herein, we introduce the use of a solid state Li₃N route to achieve the lithiation and mechanoreduction of metal fluoride based nanocomposites. The resulting prelithiation was found to be effective with the formation of xLiF:Me structures of very fine nanodimensions analogous to what is found by electrochemical lithiation. Physical and electrochemical properties of these nanocomposites for the bismuth and iron lithium fluoride systems are reported.     

Regioselective directed ortho metalation of 3H-naphto[2,1-b]pyrans. Synthesis of methylteretifolione B

The regiospecific lithiation of the 3H-naphtho[2,1-b]pyran system 1 b andits utility as a metalted tertifolione B equivalent 3 is described.     

First direct lithiation of 2-pyridylpiperazine on solid phase

[reaction: see text] The first direct lithiation of a pyridine derivative on solid phase has been realized. Metalation of polymer-bound 2-pyridylpiperazine with the BuLi-LiDMAE reagent followed by electrophilic quenching and subsequent cleavage provided a range of new useful C-6 substituted 2-piperazinylpyridines.     

The Chemistry of Heterasumanenes

Our studies on the synthesis of heterasumanenes, where benzylic carbon atoms of the sumanene are replaced by heteroatom functionalities, are summarized. Starting from triphenylene, repetitive lithiation at a bay position followed by introduction of silylene or germylene units provided the first trisila‐ and trigermasumanenes with no substituents on the skeletal carbon atoms. The synthesis of a trisilasumanene bearing six butoxy groups on the skeletal carbon atoms was also accomplished by our original sila‐Friedel–Crafts reaction. A heterasumanene bearing three different heteroatom functionalities was also prepared from triphenylenothiophene by a sequential lithiation method, even though protecting groups were necessary to prevent lithiation at the α‐carbon atoms of the dibenzothiophene unit. Structural analysis and optical properties of the novel heterasumanenes are also described.

     

A simple and efficient method for synthesis of 5-substituted 2'-deoxyuridine nucleosides using metal-halogen exchange reaction of 5-iodo-2'-deoxyuridine sodium salt

Treatment of the sodium salt of 2'-deoxy-3', 5'-bis-O-(tert-butyldimethylsilyl)-5-iodouridine (3) with n-BuLi effected regioselective lithiation at the 5-position and the following reaction with various electrophiles afforded 5-substituted 2'-deoxyuridines including 1b, the precursor of stable spin-labeled 1a, in good yields.     

A new efficient route to 2-substituted azulenes based on sulfonyl group directed lithiation

Directed lithiation of p-tolyl 1-azulenyl sulfone (1) at the 2-position of the azulenyl group was achieved by using lithium 2,2,6,6-tetramethylpiperidide (LTMP). The azulenyllithium thus generated could be efficiently trapped with various electrophiles to form 2-substituted derivatives 2 in moderate to good yields. p-Tolyl 2-trimethylsilyl-1-azulenyl sulfone (2a) was transformed into cyclic sulfone derivative 3a through the directed lithiation in the p-tolyl group and subsequent intramolecular ring closure at the 8-position. 2-(Phenylsulfanyl)-1-azulenyl p-tolyl sulfone (2b) suffered from desulfonylation to form 2-phenylsulfanylazulene (4). The Suzuki coupling reaction of 2-iodo-1-azulenyl p-tolyl sulfone (2d) with arylboronic acids followed by desulfonylation efficiently gave 2-arylazulenes 10.     

Organolithium-mediated diversification of peptide thiazoles

[Reaction: see text] We report a one-step, racemization-free method for the diversification of peptide thiazoles via direct lithiation of the thiazole ring. The method is compatible with N-Boc, N-trityl, carboxylic ester, and carboxamide protecting groups and has been used to directly functionalize the thiazole ring of cyclopeptide natural products.     

Addition of lithioimidazoles to isocyanates followed by Pd-coupling: access to 4-substituted imidazole-2,5-dicarboxamides

Facile access to 4-substituted N-butyl 2,5-dicarboxamides is achieved via direct lithiation of N-butyl imidazole and subsequent quenching with isocyanates followed by Pd-catalyzed coupling reactions.     

Synthesis and EPR studies of 2-N-tert-butylaminoxylpurine derivatives

[Structure: see text] 2'-Deoxyribofuranosylpurine derivatives bearing an N-tert-butylaminoxyl group (1a and 2a) were synthesized via oxidation of the corresponding N-tert-butylhydroxylamines (1b and 2b), which were synthesized by lithiation of 8-TIPS-6-chloropurine (3) at the 2-position and the following reaction with 2-methyl-2-nitrosopropane. Treatment of 1b and 2b with 1 equiv of NaIO4 resulted in efficient formation of 1a and 2a, which were isolated as purple and red solids, respectively. The EPR spectra of 1a showed pH dependency due to structural change of purine moiety.     

New synthesis of 2-aryl-3-substituted benzo[b]furans from benzyl 2-halophenyl ethers

Treatment of benzyl 2-halophenyl ethers with 3 equiv of t-BuLi results in Li-halogen exchange and lithiation at benzylic methylene simultaneously. These dianions do not undergo Wittig rearrangement and can be trapped with electrophiles. Their reactions with carboxylic esters afford the corresponding 2-aryl-3-hydroxy-2,3-dihydrobenzo[b]furans as a mixture of diastereoisomers. Subsequent acid-catalyzed or mediated dehydration gives moderate to good overall yield of a variety of 2-aryl-3-substituted benzo[b]furans.     

The preparation of synthetically useful carbonyl-protected δ- and -lithio ketones via reductive lithiation

The aromatic radical-anion induced reductive lithiation of the acetals or thioacetals of δ- and -(phenylthio)ketones provides δ- and -lithioketone equivalents. Primary and tertiary organolithiums have been generated and the ketone function may be part of a ring. The major synthetic use demonstrated in this report is the conversion to mixed heterocuprates which react with acyl chlorides to yield mono-protected 1,6- or 1,7-diketones. The cuprates also undergo conjugate addition to enones.     

Dianion metallation reactions of n,n-dimethylvanillylamine and n,n-dimethylisovanillylamine

The utility of dianion chemistry in the synthesis of polyfunctional aromatics is demonstrated by the direct lithiation of the vanillylamine 1 and by the metal-halogen exchange reaction of the bromo isovanillylamines 9 and 10.     

Regioselective protection at N-2 and derivatization at C-3 of indazoles

Indazoles are regioselectively protected at N-2 by a 2-(trimethylsilyl)ethoxymethyl (SEM) group using novel conditions. The SEM group can efficiently direct regioselective C-3 lithiation, and the resulting nucleophile can react with a wide range of electrophiles to generate novel indazole derivatives. The SEM group can be removed by treatment with TBAF in THF or aqueous HCl in EtOH.     

A (-)-sparteine-directed highly enantioselective synthesis of boroproline. Solid- and solution-state structure and properties

A two-step, direct asymmetric synthesis of the trifluoroacetate ammonium salt of boroproline is reported. (-)-Sparteine-mediated lithiation of N-Boc-pyrrolidine afforded N-Boc-aminoboronic acid in good yield and enantioselectivity as determined by HPLC (pinanediol ester). Deprotection using TFA yielded the ammonium salt; full characterization data are presented, and the structure in aqueous solution and the occurrence of a B-N species are discussed.     

Synthesis of 2-heterosubstituted quinazolinone atropisomeric phosphine ligands by direct lithiation of a 2-unsubstituted quinazolinone system

The syntheses of 2-heterosubstituted atropisomeric quinazolinone phosphine ligands 7e–g have been achieved in good yield by the straightforward direct lithiation of the 2-unsubstituted quinazolinone ligand 7d followed by electrophilic substitutions.