A new strategy for the synthesis of coumarin- and quinolone-annulated pyrroles via Pd(0) mediated cross-coupling followed by Cu(I) catalyzed heteroannulation

The sequential coupling and cyclization reactions between aryl halides and (trimethylsilyl)acetylene (TMSA) with concurrent elimination of the TMS substituent, allows a straightforward synthesis of substituted pyrano[3,2-e]indolone and pyrrolo[3,2-f]quinolone derivatives in excellent yields.     

Reaction of Hexamethyldisilazane with Borane in Tetrahydrofuran

Hexamethyldisilazane 1 reacts with borane in tetrahydrofuran (THF? BH₃, 2 ) first by formation of an adduct (Me₃Si)₂NH? BH₃ ( 3 ), and then either to the N,N-bis-(trimethylsilyl)-μ-aminodiborane 5 or to the mixture of 5 and N-trimethylsilyl-μ-aminodiborane(6) 6 , depending on the reaction conditions. The compounds 5 and 6 can be quantitatively converted to the N,N′,N″-tris(trimethylsilyl)borazine 4 . Three intermediates can be identified, namely N,N-bis(trimethylsilyl)borane 7 , N,N-bis(trimethylsilyl)amino(N′-trimethylsilylamino)borane 8 and N-trimethylsilylaminoborane-trimer. All products and intermediates were characterized by multinuclear NMR spectroscopy, and coupling constant ¹J(²⁹Si, ¹⁵N) were measured from ²⁹Si NMR spectra by using the Hahn-echo-extended (HEED) INEPT pulse sequence.     

Structure and dynamics of t-butyldimethylsilyl amides

A series of N-alkyl- and N-aryl-t-butyldimethylsilyl amides have been prepared by amination and their structures determined by IR and NMR spectroscopy. Like their trimethylsilyl counterparts, the N-alkyl derivatives exist as amides while the N-aryl derivates exist as amide/imidate mixtures. The percentage of imidate and the free energies of activation for the imidate/amide exchange in the aryl derivatives are greater than those in the trimethylsilyl derivatives. The barriers to rotation in the amide form of the aryl derivatives are similar to those of the trimethylsilyl derivatives. The barrier for rotation in t-butyldimethylsilyl-N-methyl formamide, however, is lower than that of the trimethylsilyl derivative. Isomer ratios and free energies of activation are rationalized in terms of the steric effect of the t-butyl group.     

Bis(difluorphosphoryl)amin und einige N-Derivate

Bis(difluorophoryl)amine and Some N-Derivatives Preparation and chemical and physical properties of bis(difluorophosphoryl)-amine, its lithium salt and of the N methyl and N trimethylsilyl derivatives are described. The chemical shifts δ(³¹P), δ(¹⁹F), δ(¹H) and numerous coupling constants are tabulated and discussed.     

Synthesis of <Emphasis Type="Italic">N</Emphasis>-and <Emphasis Type="Italic">C</Emphasis>-trimethylsilyl-substituded anililes

N-Metallation of bromoanilines with ethylmagnesium bromide followed by a reaction with trimethylchlorosilane provided N-mono and N-bis(trimethylsilyl)bromoanilines depending on the structure of substrate. The metallation of bissilylated bromoanilines with butyllithium permitted the introduction of a trimethylsilyl substituent in the aromatic ring. Previously unknown 2-bromo-N,N-bis(trimethylsilyl)aniline, 2,6-dibromo-N-trimethylsilylaniline, 2,6-dibromo-N,N-bis(trimethylsilyl)aniline, 2-bromo-6-trimethylsilylaniline, 2-bromo-6-trimethylsilyl-N,N-bis(trimethylsilyl)aniline, 2-bromo-6-trimethylsilyl-N-trimethylsilylaniline, 2,4,6-tribromo-N-trimethylsilylaniline, and 2,4,6-tribromo-N,N-bis(trimethylsilyl)aniline were prepared. The structures of the compounds obtained were established by the chromato-mass spectrometry and ¹H, ¹³C, and ²⁹Si NMR spectroscopy.     

(Chloromethyl)alkoxysilanes,Silethanes, and Silethenes in the Synthesis of Linear and Heterocyclic Compounds

The use of N,N-dimethylhydrazine or its trimethylsilyl derivatives in silylation, silamethylation, silethenation, and transsilylation allows synthesis of previously unknown linear and heterocyclic compounds.     

Palladium‐Catalyzed One‐Pot Three‐ or Four‐Component Coupling of Aryl Iodides,Alkynes, and Amines through CN Bond Cleavage: Efficient Synthesis of Indole Derivatives

An efficient synthesis of N‐substituted indole derivatives was realized by combining the Pd‐catalyzed one‐pot multicomponent coupling approach with cleavage of the C(sp³)?N bonds. Three or four components of aryl iodides, alkynes, and amines were involved in this coupling process. The cyclopentadiene–phosphine ligand showed high efficiency. A variety of aryl iodides, including cyclic and acyclic tertiary amino aryl iodides, and substituted 1‐bromo‐2‐iodobenzene derivatives could be used. Both symmetric and unsymmetric alkynes substituted with alkyl, aryl, or trimethylsilyl groups could be applied. Cyclic secondary amines such as piperidine, morpholine, 4‐methylpiperidine, 1‐methylpiperazine, 2‐methylpiperidine, and acyclic amines including secondary and primary amines all showed good reactivity. Further application of the resulting indole derivatives was demonstrated by the synthesis of benzosilolo[2,3‐b]indole.     

Investigation of N-nitrohydrazines by the NMR method

Functionally substituted N-nitrohydrazines were studied by heteronuclear NMR. It was shown that all the investigated products from nitration of the trimethylsilyl derivatives of functionally substituted hydrazines contain the N-NO₂ fragment. The chemical shift of the nitrogen atoms of the hydrazine fragment in the¹⁵N NMR spectra and the spin-spin coupling constants were used as the main tests for structural identification. It was established that the number of recordable conformers decreases in the transition from the trimethylsilyl phenylhydrazine derivatives to the nitrohydrazines as a result of the conformational flexibility of the N(NO₂)CO fragment.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 9, pp. 2024–2031, September, 1991.     

The reductive dimerization of some 1,3-dienes and of 1,3,5-cycloheptatriene in the presence of trimethylchlorosilane: a DFT investigation

Treatment of 1,3-dienes and 1,3,5-cycloheptatriene by chlorotrimethylsilane in the presence of wire of lithium led mainly to reductive dimerization with formation of bis(allylsilane) derivatives. Bis-silyl compounds obtained: from 1,3-butadiene, 1,8-bis(trimethylsilyl)-2,6-octadiene (70%); from isoprene, (Z,Z)-2,7-dimethyl-1,8-bis(trimethylsilyl)-2,6-octadiene (44%) and 2,6-dimethyl-1,8-bis(trimethylsilyl)-2,6-octadiene (19%); from butadiene-isoprene mixture (1:1), 3-methyl-1,8-bis(trimethylsilyl)-2,6-octadiene (55%); from 2,3-dimethylbutadiene, (E,E)-2,3,6,7-tetramethyl-1,8-bis(trimethylsilyl)-2,6-octadiene (36%), from 1,3-cyclohexadiene, 4,4′-bis(trimethylsilyl)-bicyclohexyl-2,2′-diene (48%); from 1,3,5-cycloheptatriene, 1,1′-bi[(S^∗,S^∗)-6-(trimethylsilyl)cyclohepta-2,4-dien-1-yl] (53%). The structure of the various intermediates (radical anion, dianion, silylated radical, silylated anion) has been established by calculations at the B3LYP/6-311++G(d,p) level of theory with zero-point energy correction. These results are in accordance with a pathway including the formation of a radical anion, its silylation furnishing to a γ-silylated allylic radical followed by a dimerization reaction in the head to head manner.     

Peculiarities of the reaction of alkali metal bis(trimethylsilyl)amides with halobenzenes

Lithium and sodium bis(trimethylsilyl)amides react with fluoro-, bromo-, and chlorobenzenes in THF or toluene to give a mixture of N,N-bis(trimethylsilyl)aniline and N,2-bis(trimethylsilyl)aniline. The latter compound is resulted from 1,3-shift of the trimethylsilyl group from nitrogen to ortho-carbon atom of the benzene ring. Effects of the solvent, halogen, and alkali metal nature as well as the reaction conditions on the ratio of isomers were examined. Reaction of iodobenzene with sodium bis(trimethylsilyl)amide in THF produces N,N-bis(trimethylsilyl)aniline and 2-iodo-N,N-bis(trimethylsilyl)aniline, while in toluene a mixture of three products, two indicated above and N,N-bis(trimethylsilyl)benzylamine, was obtained.     

Palladium-catalyzed synthesis of 2-allylindole and 2-allylbenzofuran derivatives from 2-((trimethylsilyl)ethynyl)arenes

A new protocol for the synthesis of 2-allylindole and 2-allylbenzofuran derivatives has been developed from readily accessible starting material, 2-((trimethylsilyl)ethynyl)arenes via Pd-catalysis. The presence of trimethylsilyl group in the alkyne is vital for this reaction. Stereoselectivity of 2-allylindole derivatives is controlled by the use of different nitrogen-protecting groups for 2-((trimethylsilyl)ethynyl)aniline. The CO₂Me protection gives Z-isomers, whereas acetyl protection gives E-isomers.     

An efficient PyAOP-based C4-amination method for direct access of oxidized 5MedC derivatives

In the past decade, synthetic oxidized ^5-MedC nucleosides and their derivatives have become essential tools for epigenetic research. The low efficacy of both conventional and newly reported BOP methods on C⁴-amination of these specific oxidized ^5-MedU substrates urged us to systematically investigate how the nature of onium salt-based coupling reagents affects the C⁴-amination of pyrimidine nucleobases and lead us to the findings that different onium coupling reagents result in the formation of distinctive activation intermediates and PyAOP is much more potent than BOP in both activation and aminolysis steps. Direct amination without the need of ribose protection, ultrafast activation, tolerance to aqueous N-nucleophiles, and excellent yields for diverse oxidized ^5MedC derivatives are the advantages of this PyAOP-based C⁴-amination method.     

Preparation and Regioselective Metalation of Bis(trimethylsilyl)methyl‐Substituted Aryl Derivatives

A range of bis(trimethylsilyl)methyl‐substituted aryl derivatives was prepared by using a Kumada–Corriu cross‐coupling reaction. The regioselective metalation of the resulting bis(trimethylsilyl)methyl‐substituted aryl derivatives bearing this bulky silyl group allowed the generation of functionalized aromatics. A regioselective switch in the presence or in the absence of the bis(trimethylsilyl)methyl group has been demonstrated. Furthermore, this silyl group was converted into a formyl group or a styryl group, enhancing the scope of application of such bis(trimethylsilyl)methyl‐substituted arenes.     

Hydrazine derivatives in the synthesis of linear and heterocyclic compounds

N-Siloxycarbonylation, transamination, carboxylation, silylation, and condensation of N,N-dimethylhydrazine, 1-methyl-1-[2-(1-methylhydrazino)ethyl]hydrazine, N-methyl-2-(1-methylhydrazino)ethanamine, and some their trimethylsilyl derivatives resulted in the formation of previously unknown linear and heterocyclic compounds.     

Synthesis of modified pyrimidine nucleosides via Vorbrüggen-type N-glycosylation catalyzed by 2-methyl-5-phenylbenzoxazolium perchlorate

Several acidic azolium salts prepared from oxazole, thiazole, and imidazole derivatives were investigated as catalysts in N-glycosylation reaction using a silylated modified pyrimidine and an acylated ribose or glucose to afford the corresponding pyrimidine nucleoside. Among the salts, 2-methyl-5-phenylbenzoxazolium perchlorate showed the highest catalytic activity. This salt is a nonhygroscopic crystalline compound that shows higher activity than the frequently used trimethylsilyl triflate. Reactions with this salt can be conducted in gram scales.     

An efficient convergent synthesis of adenosine-5′-N-alkyluronamides

Herein we report an efficient synthesis of adenosine-5′-N-alkyluronamides in which an enzyme-mediated deacetylation reaction is a key to the selective modification of the 5′-N-position, prior to coupling the ribose and purine components via a microwave-assisted Vorbrüggen coupling. This approach provides access to highly functionalised adenosines with 2- and N⁶-substitutents, which can be incorporated before or after the ribose-coupling step. In all cases the microwave-assisted Vorbrüggen coupling conditions afforded anomerically pure purine ribosides in good to excellent yields.     

Efficient access to β- and γ-carbolines from a common starting material by sequential site-selective Pd-catalyzed C–C,C–N coupling reactions

Two efficient and practical approaches are reported for the synthesis of β- and γ-carboline derivatives from 3,4-dibromopyridine as a common starting material. The β-carbolines were prepared by site-selective Pd-catalyzed C–C coupling with o-bromophenylboronic acid and subsequent cyclization by double C–N coupling with amines. γ-Carbolines were prepared from the same starting material by C–N coupling with anilines and subsequent annulation by domino C–C/C–N coupling with o-bromophenylboronic acid.     

Catalysis by zeolite leading to the construction of thiazole ring: an improved synthesis of 4-alkynyl substituted thiazoles

Zeolite H-beta facilitated the reaction of α-chloro acetyl chloride with 1,2-bis-trimethyl silyl acetylene to give 1-chloro-4-(trimethylsilyl)but-3-yn-2-one which on treatment with thioacetamide afforded 2-methyl-4-[(trimethylsilyl)ethynyl]thiazole. l-Proline on the other hand facilitated the coupling reaction of 2-methyl-4-[(trimethylsilyl)ethynyl]thiazole with (hetero)aryl halides (modified Sonogashira reaction) under Pd-Cu catalysis in the presence of aqueous K₂CO₃ affording an improved method for the synthesis of corresponding 4-alkynyl substituted thiazole derivatives.     

Synthesis of Potentially Biologically Active 6‐(1,3‐Butadiynyl)purines

1,3‐Alkadiynyl(trimethyl)silanes were prepared by the Negishi or Sonogashira reactions of bromoethynyl(trimethyl)silane with several terminal alkynes in 34–75% yield. However, the direct Hiyama coupling of these compounds with 6‐iodopurine derivatives has not been successful. Therefore, a modified Sonogashira reaction using TBAF or CsF for in situ removal of the trimethylsilyl group has been utilized. This methodology afforded the desired 6‐(1,3‐butadiynyl)purines in 47–87% yield.     

An efficient large-scale synthesis of gemcitabine employing a crystalline 2,2-difluoro-α-ribofuranosyl bromide

An efficient large-scale synthesis of gemcitabine was achieved without chromatography or fractional crystallization. The key steps include stereospecific conversion of a novel β-ribofuranosyl phosphate into a highly crystalline α-ribofuranosyl bromide and coupling of the α-ribofuranosyl bromide and trimethylsilyl cytosine to produce a β-nucleoside. p-Phenylbenzoyl group was introduced for the protection of one of hydroxy groups in order to enhance the crystallinity of intermediates. Continuous removal of trimethylsilyl bromide, generated during the coupling reaction, by distillation from the reaction medium substantially enhanced the β-selectivity of the crucial coupling reaction.