Coupling reactions of aryl and heteroaryl halides with a trimethylsilylethynylpyrazine

By the coupling reactions of trimethylsilylacetylene and 2-chloro-3,6-diisobutylpyrazine, 3,6-diisobutyl-2-trimethylsilylethynylpyrazine or 1,2-bis(3,6-diisobutylpyrazin-2-yl)acetylene was obtained, depending on the solvent used. The former substance coupled with various aryl and heteroaryl halides to give 1-aryl-2-pyrazin-ylacetylenes.     

Linchpin construction of unsymmetrical 1,4-alkynediols

A one-pot preparation of unsymmetrical 1,4-alkynediols such as 2a by the coupling of trimethylsilylacetylene and two different aldehydes or ketones is reported. The dilithiated species 5 is generated by the sequential addition of the first aldehyde or ketone 1b to a solution of lithium trimethylsilylacetylide, followed by the addition of methyllithium, which removes the trimethylsilyl protecting group. Addition of the second aldehyde or ketone then leads to the unsymmetrical 1,4-alkynediol 2a.     

Palladium catalysed regio- and stereoselective synthesis of (E)-4-aryl-1,3-bis(trimethylsilyl)but-3-en-1-ynes

A practical and general synthetic approach to a series of 4-aryl-but-3-en-1-ynes is described. In the presence of palladium complexes a variety of aryl bromides (or iodides) undergo coupling with two equivalents of trimethylsilylacetylene with the formation of (E)-4-aryl-1,3-bis(trimethylsilyl)but-3-en-1-ynes. The protocol is simple, efficient, and affords synthesis of regio- and stereoselectively target products in good to high yields.     

3-炔基咪唑并[1,2-b]哒嗪的简便合成

以咪唑并[1,2-b]哒嗪为原料,与N-碘代丁二酰亚胺在三氟乙酸/二氯甲烷中于室温进行碘代反应制得3-碘咪唑并[1,2-b]哒嗪(3);3与三甲基硅基乙炔在Pd(OAc)_2催化下经Sonogashira偶联反应制得3-三甲基硅基乙炔基咪唑并[1,2-b]哒嗪(4);4在碳酸钾作用下脱除三甲基硅基合成了3-炔基咪唑并[1,2-b]哒嗪,总收率61.2%,其结构经~1H NMR和HR-MS确证。     

Polymerization of trimethylsilylacetylene by WCl6-based catalysts

The polymerization of trimethylsilylacetylene was investigated by using W and Mo catalysts. Mixtures of WCl₆ with appropriate organometallic cocatalysts such as n-Bu₄Sn and Et₃SiH at 1:1 molar ratio provided poly(trimethylsilylacetylene) in high yields. On the other hand, MoCI₅ gave mainly methanol-soluble oligomers even in the presence of these cocatalysts. The polymer formed was a partly insoluble yellow powder, and the molecular weight of the soluble fraction was about 7000. The IR, ¹H-NMR, and ¹³C-NMR spectra supported the polymer structure, (CH = CSiMe₃)_n. Protodesilylation of poly(trimethylsilylacetylene) afforded a new polymer containing both acetylene and trimethylsilylacetylene units.     

Palladium-catalyzed Coupling between Aryl Halides and Trimethylsilylacetylene Assisted by Dimethylaminotrimethyltin

Palladium‐catalyzed coupling between aryl halides, especially less reactive ones or N‐heteroaryls, and trimethylsilylacetylene in the presence of dimethylaminotrimethyltin generated the coupled products in high yields. The reaction does not need CuI and base as auxiliary agents.     

A concise formal total synthesis of mappicine and nothapodytine B via an intramolecular hetero Diels-Alder reaction

A six-step formal total synthesis of a natural alkaloid, mappicine (3), has been achieved. The highlight of our synthetic strategy is an intramolecular hetero Diels-Alder reaction that was used for the construction of the CD ring system of mappicine (3). In addition, it was demonstrated that the Sonogashira coupling reaction of 2-chloro-3-hydroxymethylquinoline (8c) with trimethylsilylacetylene proceeded at room temperature in excellent yield.     

A copper- and amine-free sonogashira reaction employing aminophosphines as ligands

An efficient Pd-catalyzed Sonogashira coupling reaction was achieved in the absence of a copper salt or amine with an inorganic base and easily prepared, air-stable aminophosphine ligands in commonly used organic solvents; good to excellent yields were obtained. Under optimized reaction conditions, the Sonogashira coupling reaction occurred selectively when an enyne substrate was employed and no Heck reaction product was detected; acetone-masked acetylene and trimethylsilylacetylene can also be efficiently coupled, providing a method to make terminal alkynes.     

Synthesis of 8-bromo-5,12-tetracenequinone and 2-bromotetracene derivatives

A series of bromotetracenequinones 1 and bromotetracenes 2 were prepared from 4-bromophthalic anhydride. The parent tetracenequinone 1a and tetracene 2a were sparingly soluble in organic solvents. In contrast, dipropyl-substituted tetracenequinone 1b and tetracene 2b were a little more soluble. Preparation of dihexyl-substituted tetracene 2c proved to be difficult. Sonogashira coupling of 1b with trimethylsilylacetylene afforded the corresponding product.     

Synthesis and Characterization of 2,5-Bis(2-pyridyl)thiophene

2-[2-(Trimethylsilyl)ethynyl] pyridine ( 6 ) was prepared in 95% yield by reaction of 2-bromopyridine with trimethylsilylacetylene in triethylamine in the presence of bis(triphenylphosphine)Palladium(II) chloride and Copper(I) iodide. Desilylation of ( 6 ) by refluxing with sodium hydroxide in methanol (yield 95%) of 2-ethynylpyridine ( 5 ). Oxidative coupling of ( 5 ) in pyridine by oxygen in the presence of Copper(I) chloride gives 70% yield of 1,4-bis(2-pyridyl)1,3-butadiyne ( 4 ). Reaction of 4 with sodium sulfide affords 100% of 2,5-bis(2-pyridyl) thiophene ( 1 ).     

Rapid homogeneous-phase Sonogashira coupling reactions using controlled microwave heating

A microwave-enhanced, rapid and efficient homogeneous-phase version of the Sonogashira reaction is presented. It has been applied to the coupling of aryl iodides, bromides, triflates, and aryl chloride, as well as pyridine and thiophene derivatives with trimethylsilylacetylene. Excellent yields (80-95%) for substrates containing a large variety of substituents in different positions are obtained in 5-25 min.     

Asymmetric synthesis of alpha,alpha-dibranched propargylamines by acetylide additions to N-tert-butanesulfinyl ketimines

Addition of lithium acetylides prepared from 1-pentyne, phenylacetylene, and trimethylsilylacetylene to diverse N-tert-butanesulfinyl ketimines affords a range of alpha,alpha-dibranched propargyl sulfinamides in generally good yields (up to 87%) and with high diastereoselectivities (up to >99:1). Acidic cleavage of the tert-butanesulfinyl group provides the free alpha,alpha-dibranched propargylamines.     

Enantiospecific synthesis of the phospholipase A2 inhibitors (-)-cinatrin C1 and (+)-cinatrin C3

The enantiospecific synthesis of (-)cinatrin C1 (3) and (+)-cinatrin C3 (5) from the D-arabinose derivative 9 is described. The stereochemistry at C2 was introduced via a chelation-controlled addition of a carbanion to alpha-hydroxy ketone 8. The best selectivity was achieved by use of the Grignard reagent derived from trimethylsilylacetylene. Transformation of the terminal alkyne into methyl ester 17 followed by acetal hydrolysis and selective lactol oxidation gave cinatrin C1 dimethyl ester (7). Base hydrolysis and acid induced relactonization then gave a 1:1 mixture of cinatrins C1 (3) and C3 (5).     

New syntheses of the C,D-ring pyrromethenones of phytochrome and phycocyanin

Pyrromethenone 7, the C,D-ring segment of phytochrome (Pr, 4), has been prepared in an efficient fashion employing three new strategies. Each of these has potential advantages for the synthesis of labeled material. Our first approach is related to the Gossauer synthesis, with the difference that strong alkali is avoided in the condensation of the C- and D-ring components 8 and 17. The key silyloxypyrrole 17 was readily prepared on multigram scales beginning with inexpensive butyrolactone (10). A second synthesis began with 2-acetylbutyrolactone (41). The key steps involved conversion of 41 to the Z-enoltriflate 42, followed by Pd(0)-catalyzed coupling with trimethylsilylacetylene, p-chlorophenylselenide ring opening, and finally, amidation to afford the ring-D synthon 45 having the proper geometry and oxidation state for conversion to 7. Sonogashira coupling of 45 with the iodopyrrole 22, followed by oxidative elimination, and F(-)-induced 5-exo-dig cyclization of the resultant pyrroloalkyne 47, then completed the synthesis. In similar fashion, we have also prepared pyrromethenone 6, the C,D-ring segment of phycocyanin (2).     

Photolysis of organopolysilanes. Photochemical formation and reactions of 1-trimethylsilyl-1-phenyl-1-silacyclopropene derivatives

The photolysis of tris(trimethylsilyl)phenylsilane (I) in the presence of 1-hexyne, 3,3-dimethyl-1-butyne, trimethylsilylacetylene, 3-hexyne, 1-trimethylsilylpropyne, 1,2-bis(trimethylsilyl)acetylene and 2,2,5,5-tetramethyl-3-hexyne afforded the respective silacyclopropenes. The silacyclopropenes produced from monosubstituted acetylenes underwent photochemical isomerization to give disilanylacetylene derivatives, via a 1,2-hydrogen shift in the silacyclopropene ring. Irradiation of I in the presence of 3-hexyne, 1-trimethylsilylpropyne or 2,2,5,5-tetramethyl-3-hexyne, gave the corresponding silacyclopropenes which could be isolated by preparative GLC. The silacyclopropene from 1,2-bis(trimethylsilyl)acetylene, however, readily underwent thermal rearrangement to give [bis(trimethylsilyl)phenylsily] trimethylsilylacetylene via a 1,2-trimethylsilyl shift. This type of rearrangement was also found in the photochemical process.     

5-Nitroisocoumarins from tandem Castro-Stephens coupling—6-endo-dig cyclisation of 2-iodo-3-nitrobenzoic acid and arylethynes and ring-closure of methyl 2-alkynyl-3-nitrobenzoates with electrophiles

Reaction of 2-iodo-3-nitrobenzoic acid with arylalkynyl copper(I) reagent gave 3-aryl-5-nitroisocoumarins. Castro-Stephens coupling was followed by in situ Cu-catalysed ring-closure. ¹H NMR and X-ray crystallography showed the cyclisations to be 6-endo, contrasting with reports of 5-exo cyclisation of analogous 2-iodobenzoate esters with alkynes. Sonogashira couplings of methyl 2-iodo-3-nitrobenzoate with phenylacetylene and with trimethylsilylacetylene gave the corresponding 2-alkynyl-3-nitrobenzoate esters. With HgSO₄, the phenylalkyne underwent 6-endo cyclisation to give 5-nitro-3-phenylisocoumarin. The disubstituted alkyne esters gave 4-phenylselenylisocoumarins with PhSeCl. 5-Nitro-3-phenyl-4-phenylselenylisocoumarin shows significant sterically-driven distortion of the isocoumarin ring. Reaction of methyl 3-nitro-2-phenylethynylbenzoate with ICl gave the 4-iodoisocoumarin. Thus the nitro group tends to direct these electrophile-driven cyclisations towards the 6-endo mode.     

A general procedure for the synthesis of alkyl- and arylethynyl-1,2,3-triazole-fused dihydroisoquinolines

A general procedure for the synthesis of the title compounds has been devised starting from the available 2-halophenylethyl azides, by means of click reactions with trimethylsilylacetylene or 1-trimethylsilyl-1,3-butadiyne followed by a transition metal-catalyzed functionalization of C-H bond. A further extension of this procedure led us to devise the synthesis of more complex 4,4'-bitriazole-fused dihydroisoquinolines.     

Improved functional group compatibility in the palladium-catalyzed synthesis of aryl amines

[reaction: see text] The use of Pd2dba3 with bulky, electron-rich ligands 1 or 2 and LiN(TMS)2 as the base for the coupling of amines with aryl halides containing hydroxyl, amide, or enolizable keto groups is described. This protocol expands the utility of palladium-catalyzed C-N bond formation by allowing for the use of aryl halides containing these functional groups, obviating the need for protecting group manipulations.     

Elaboration of diaryl ketones into naphthalenes fused on two or four sides: a naphthoannulation procedure

Transition metal-catalyzed double ring closures of 1,1-diaryl-2,2-diethynylethylenes yield polycyclic aromatic hydrocarbons and heterocycles that contain a newly formed naphthalene ring system embedded in a larger polycyclic network. The diynes required for this procedure are readily synthesized from diaryl ketones by the Corey-Fuchs olefination and subsequent Sonogashira coupling with trimethylsilylacetylene followed by desilylation. This procedure provides easy access to new compounds such as 3,11-di-tert-butyl[4]helicene and 1,8,9-perinaphthothioxanthene. Double naphthoannulation of 9,10-anthraquinone by this procedure closes four new benzene rings in a single operation to give coronene, although the yield in this case is presently low.     

Intramolecular carbometallation of grignard reagents having the terminal trimethylsilylacetylene group

Reaction of 6-bromo-1-trimethylsilyl-1-hexyne with magnesium affords the corresponding Grignard reagent whose C-Mg bond intramolecularly adds to the trimethylsilylacetylene moiety in 5-Exo-Dig manner and suprafacially. The reaction can be applied to the synthesis of some cycloalkanes having stereo-defined alkylidene substituents.