Cross alkyne

Witulski introduced a novel protocol for crossed alkyne cyclotrimerizations of systems such as 87 mediated by Grubb s catalyst to produce 4,6-disubstituted indolines 88 <00CC1965>. Interestingly, use of Wilkinson s catalyst [RhCl(PPhj)3] allows for the regioselective synthesis of the corresponding 4,5-substituted isomers. 

Crossed-alkyne cyclotrimerizations between the diynes 580 and the monoalkynes 581 with a catalytic amount of RhClfPPhsls afforded substituted carbazoles 582. The high efficiency of the carbazole formation could be rationalized by the conformational restrictions present in the diynes 580 (561) (Scheme 5.27). 

Witulski and Alayrac reported the synthesis of clausine C (clauszoline-L) (101) by a rhodium-catalyzed alkyne cyclotrimerization of diyne 1014 and propiolic ester 635 (561). Analogous to the hyellazole (245) synthesis (see Scheme 5.75), the diyne precursor 1014 required for this key cyclotrimerization reaction was obtained starting from readily available 2-iodo-5-methoxyaniline. Using Wilkinson s catalyst, [RhClfPPhsls], crossed-alkyne cyclotrimerization of 1014 and 635 led to N-tosylclausine C (1015) in 78% yield in an isomeric ratio of 3.8 1. Finally, deprotection of the tosyl group with TBAF in refluxing TFIF afforded clausine C (clauszoline-L) (101) (561) (Scheme 5.147). 

Kaneta, N., Hikichi, K., Asaka, S.-i., Uemura, M., Mori, M. Novel synthesis of disubstituted alkyne using molybdenum catalyzed cross-alkyne metathesis. Chem. Lett. 1995,1055-1056. 

Cross-alkyne coupling provides a net two symmetrical alkynes. ... 

Alkyne metathesis. Substituted tolanes are formed from alkyl aryl acetylenes. Cross-alkyne coupling provides a new route to unsymmetrical disubstituted alkynes from two symmetrical alkynes. ... 

Members of the cannabinoid class of natural products were accessed using a crossed [2 + 2 + 2] cycloaddition, as shown for the synthesis of cannabinol (86) (Scheme 7.18) [28], Sterically encumbered substituents, on both the diyne and the monoyne reaction partners, were used to direct the regioselective outcome of this crossed alkyne cyclotrimerization. The Cp RuCl(cod) complex (10 mol %) was employed as catalyst, allowing the reaction of diyne 84 with an excess of propar-gyltrimethylsilane under microwave conditions to deliver the pyrane 85 in 88% yield as a single regioisomer. The latter was used as a synthetic intermediate to access cannabinol (86) as well as cannabinodiol within five additional synthetic steps. 

Clausine C (107) was synthesized in six steps with an overall yield of 40%, starting from commercially available iodoaniline 104. Notably, the yne-ynamide formation was realized though direct N-ethynylation of the corresponding tosylamide generated from 104 using the readily available alkynyliodonium salt 105. Thereafter, the rhodium-catalyzed crossed alkyne cyclotrimerization of 106 with methyl propri-olate furnished the corresponding crossed cycloaddition products in the ratio 4 1... 

All of the syntheses above profited from an exceedingly regioselective crossed alkyne cyclotrimerization of differently substituted yne-ynamides with... 

The crossed alkyne cyclotrimerization of 119 with the electron-deficient... 

Numerous articles have appeared in the literature regarding carbene complexes in the context of olefin metathesis reactions. Thus, there are reports on the synthesis of a variety of new metathesis catalysts " (including surface-sup-ported complexes and a water-soluble species ), several articles the use of carbene complexes in ring-closing, ring-opening, and olefin crossmetathesis,and a report on the use of Grubbs catalyst in a crossed alkyne cyclotrimerisation reaction. ... 

Tanaka, K., Nishida, G., Wada, A. and Noguchi, K. (2004) enantioselective synthesis of axially chiral phthalides through cationic [Rh(I)(H8-binap)]-catalyzed cross alkyne cyclotrimerization. Angewandte Chemie International Edition, 43(47), 6510-6512. 

The alkynyl iodide 359 undergoes cross-coupling with a terminal alkyne to give the 1,3-diyne 360[264]. No homocoupling product is formed. This reaction offers a good synthetic method for unsymmetrical 1,3-diynes. 

The thioboration of terminal alkynes with 9-(alkylthio)-9-borabicyclo[3.3.1]-nonanes (9-RS-9-BBN) proceeds regio- and stereoselectively by catalysis of Pd(Ph,P)4 to produce the 9-[(Z)-2-(alkylthio)-l-alkeny)]-9-BBN derivative 667 in high yields. The protonation of the product 667 with MeOH affords the Markownikov adduct 668 of thiol to 1-alkyne. One-pot synthesis of alkenyl sulfide derivatives 669 via the Pd-catalyzed thioboration-cross-coupling sequence is also possible. Another preparative method for alkenyl sulfides is the Pd-catalyzed cross-coupling of 9-alkyl-9-BBN with l-bromo-l-phe-nylthioethene or 2-bromo-l-phenylthio-l-alkene[534]. 

The cis thioboration of terminal alkynes with 9-(arylthio)-9-BBN is catalyzed by Pd(Pli3P)4 in the presence of styrene. The product 136 is converted into the vinyl sulfides 137 and 138 by the treatment with MeOH or by Pd-catalyzed cross-coupling with aryl or alkenyl halides using K3PO4 in DMF[68]. No thioboration takes place with internal alkynes. 

Alkyl- and aryl-pyridazines can be prepared by cross-coupling reactions between chloropyridazines and Grignard reagents in the presence of nickel-phosphine complexes as catalysts. Dichloro[l,2-bis(diphenylphosphino)propane]nickel is used for alkylation and dichloro[l,2-bis(diphenylphosphino)ethane]nickel for arylation (78CPB2550). 3-Alkynyl-pyridazines and their A-oxides are prepared from 3-chloropyridazines and their A-oxides and alkynes using a Pd(PPh3)Cl2-Cu complex and triethylamine (78H(9)1397). 

Burger s criss-cross cycloaddition reaction of hexafluoracetone-azine (76S349) is also a synthetic method of the [CNN + CC] class. In turn, the azomethines thus produced, (625) and (626) (79LA133), can react with alkenes and alkynes to yield azapentalene derivatives (627) and (628), or isomerize to A -pyrazolines (629) which subsequently lose HCF3 to afford pyrazoles (630 Scheme 56) (82MI40401). 

The von Richter cinnoline process was further extended to solid-phase synthesis. The route began from benzylaminomethyl polystyrene and the required diverse o-haloaryl resins represented by 21 were prepared from substituted o-haloanilines. A Pd-mediated cross-coupling reaction with 21 and the alkynes provided the alkynylaryl derivatives represented by alkyne 22. The von Richter cyclization reaction with hydrobromic or hydrochloric acid in acetone/HaO and cleavage from the resin occurred in the same step to furnish the cinnoline derivatives 23 in 47-95% yield and 60-90% purity (no yield reported for each entry). 

Closely related to the Heck reaction is the Sonogashira reaction i.e. the palladium-catalyzed cross-coupling of a vinyl or aryl halide 20 and a terminal alkyne 21 ... 

Alkyne cross metathesis Acyclic diene metathesis Asymmetric ring-closing metathesis Asymmetric ring-opening metathesis Cross metathesis... 

Fig. 3a,b Typical diyne metathesis reactions ring-closing alkyne metathesis (RCAM, a) diyne cross metathesis (ACM, b)... 

Ring-Closing Alkyne Metathesis (RCAM) and Alkyne Cross Metathesis (ACM)... 

Table 2. One-Pot Hydrosilyation/Cross-Coupling of 1-Alkynes with Aryl...

A cross-coupling reactions of terminal alkynes with terminal alkenes 32 supported on Merrifield-resin (Scheme 4.5) in the presence of Grubs ruthenium initiator [Cl2(PCy3)2Ru = CHPh] provided efficient access to supported 1,3-dienes 33 which were transformed into octahydrobenzazepinones 34 via MeAlCl2 catalyzed Diels-Alder reaction [27]. 

Radical-mediated silyldesulfonylation of various vinyl and (a-fluoro)vinyl sulfones 21 with (TMSlsSiH (Reaction 25) provide access to vinyl and (a-fluoro)vinyl silanes 22. These reactions presumably occur via a radical addition of (TMSlsSi radical followed by /)-scission with the ejection of PhS02 radical. Hydrogen abstraction from (TMSlsSiH by PhS02 radical completes the cycle of these chain reactions. Such silyldesulfonylation provides a flexible alternative to the hydrosilylation of alkynes with (TMSlsSiH (see below). On oxidative treatment with hydrogen peroxide in basic aqueous solution, compound 22 undergoes Pd-catalyzed cross-couplings with aryl halides. 

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