Disubstituted alkynes, transition

The cycloaddition-isomerization procedure can be accomplished in the presence of a catalytic amount of a transition metal salt. The reactions proceed at room temperature, neither air nor water needed to be excluded. The presence of an electron-withdrawing group is not necessary to activate the dienophile as the example below shows that gold coordination increases the electrophilicity of the triple bond. The presence of a terminal alkyne should also be important. In the case of a disubstituted alkyne no reaction can be observed <00JA11553>. 

In addition to these examples, the late transition metals such as ruthenium, rhodium, and iridium have shown their effectiveness in catalyzing the PKR. In 1997, two groups independently showed that [Ru3(CO)i2] can catalyze the PKR. The group led by Murai reported the conditions that employ dioxane as a solvent " another group led by Mitsudo employed DM AC as a solvent." Both conditions required high pressure of CO (10-15 atm) and the scope is limited to the disubstituted alkynes. 

Transition metal-promoted allylzincation of disubstituted alkynes. . 901... 

For other , 1-disubstituted alkynes lacking an activating group, transition metal catalysts or promotors could be used to achieve allylzincation. 

Herein, we review nonexhaustively our contribution to the field of transition-metal-mediated heterocyclic synthesis. This chemistry is based mainly on using cyclopalladated complexes and their reactions with disubstituted alkynes that in many cases, lead to heterocyclic products by the selective intramolecular formation of carbon-carbon and carbon-heteroatom (C-N, C-O and C-S) bonds. In some instances these reactions also lead to interesting carbocyclic derivatives. Emphasis is placed on the transformations of the alkynes. When they are allowed to react with the metallated ligands, they lead in several instances to heterocyclic or carbocyclic final products. We present in particular some of the more recent results emanating from our laboratory and comment briefly on some similarities of this chemistry to other, selected and related transition-metal-mediated reactions, thus demonstrating that this field of research remains in vogue in many different research groups. 

For alkyl-substituted alkynes, there is a difference in stereochemistry between mono-and disubstituted derivatives. The former give syn addition whereas the latter react by anti addition. The disubstituted (internal) compounds are considerably ( 100 times) more reactive than the monosubstituted (terminal) ones. This result suggests that the transition state of the rate-determining step is stabilized by both of the alkyl substituents and points to a bridged intermediate. This would be consistent with the overall stereochemistry of the reaction for internal alkynes. 

In hydrogenation, early transition-metal catalysts are mainly based on metallocene complexes, and particularly the Group IV metallocenes. Nonetheless, Group III, lanthanide and even actinide complexes as well as later metals (Groups V-VII) have also been used. The active species can be stabilized by other bulky ligands such as those derived from 2,6-disubstituted phenols (aryl-oxy) or silica (siloxy) (vide infra). Moreover, the catalytic activity of these systems is not limited to the hydrogenation of alkenes, but can be used for the hydrogenation of aromatics, alkynes and imines. These systems have also been developed very successfully into their enantioselective versions. 

Thermal fragmentation of 2,5-disubstituted tetrazoles results in loss of Na and generation of a reactive nitrilimine intermediate (67). The Hammett p-values for the A -phenyl and C-phenyl rings of diaryltetrazoles (65) were +1.16 and -0.23, respectively, suggesting an unsymmetrical transition state of type (66) (68X3787). Subsequent additions of the nitrilimines to unsaturated bonds such as alkenes, imines, alkynes and nitriles give an added importance to the parent tetrazoles as synthetic precursors (Scheme 6). Among the most... 

The use of alkynes in transition metal catalyzed reactions is often complicated by their tendency to undergo cyclo-tiimerization and -tetramerization. Thus, it is useful to note that a phosphite-modified catalyst, Ni(COD)2Aris(o-phenylphenyl) phosphite (TOPP), promotes codimerization of alkynes with methylenecyclopropane and its a ylidene analogs. Both electron-rich and electron-poor alkynes participate in cycloaddition with moderate regioselectivity. Opposite regiochemistiy is sometimes observed widi disubstituted alkylidene systems (equations 97-99). 

Only recently have early transition metal propargylic complexes been recognized. The lanthanide alkyls [LnCH(SiMe4)2(i7 -C5Me5)2j (Ln = La. Ce) react with the 2-alkynes MeC=CR (R = Me, Et, "Pr) to afford 1,2-disubstituted 3-alkylidenecyclobutenes. The first step in this catalytic cy-... 

Semireduction of internal alkynes in the presence of a transition metal catalyst (e.g., Ni2B, Pd/C) provides disubstituted cw-alkenes. On the other hand, dissolving metal reduction of alkynes or reduction of propargylic alcohols with LiAlH4 or with Red-Al [sodium bis(2-methoxyethoxy)aluminum hydride] furnishes tran -disubstituted alkenes. ... 

Whereas the transition metal catalyzed cyclotrimerization and cyclotetramerization of alkynes leading to benzene or cyclooctatetraene and their derivatives is a rather common reaction, there exist only a few examples of cooligomerizations between alkynes and alkenes or 1,3-butadienes leading to 1,3- or 1,4-cyclohexadiene derivatives20S). It is therefore surprising that the [3+2]-cycloaddition between methylenecyclopropanes and alkynes, catalyzed by triarylphosphite modified Ni(0) compound, is a rather convenient method to synthesize 4-methylenecyclopentenes 206). A wide range of methylenecyclopropanes and alkynes, in the latter case mainly 1,2-disubstituted ones, can be used for these reactions (Eqs. 98-100, see p. 127-128). 

The general reaction equation for alkene metathesis in a simple system, cross-metathesis of two different disubstituted alkenes, is depicted in Scheme 1. In this reaction, a transition metal catalyst establishes equilibrium between the starting alkenes, the ( )- and (Z)-stereoisomers of all possible substituent combinations, and ethylene. Related reaction processes have also been reported for alkynes (aikyne metathesis) and for combinations of alkenes and alkynes (enyne metathesis). Aikyne metathesis is less well developed compared to alkene metathesis and enyne metathesis. This review has been organized according to the basic modes of metathesis depicted in Scheme 2. Alkene metathesis is the more developed process and numerous examples of all the variants have been reported. Aikyne metathesis is less well developed and three variants exist aikyne cross-metathesis, aikyne metathesis polymerization, and ring-closing aikyne metathesis. 

Efficient and regioselective iron-catalyzed aerobic oxidative reactions afforded 3,5-disubstituted isoxazoles 5 from homopropargylic alcohols 4, r-BuONO as the nitrogen source, and H2O under mild conditions (140L6298).A transition metal-free one-pot synthesis of 3,5-disubstituted isoxazoles used terminal alkynes by treatment with -BuLi, then aldehydes and iodine to afford intermediate a-alkynyl ketones 6 converted into isoxazoles 7 with hydroxylamine (14JOC2049). 

The same group demonstrated that a variety of mono- and disubstituted 1-oxyindolizine derivatives 3S2 could be readily synthesized via a facile Ag-catalyzed cydoisomerization of skipped propargylpyridines 3S1 (Scheme 9.121) [300, 301]. It was suggested that this Au-catalyzed reaction involved a 5 -endo-d cyclization of the alkyne 351 activated by a jt-philic metal. Formation of the indolizine product 352 was accomplished via a subsequent proton transfer in cyclic vinylmetal zwitterion 354 (Scheme 9.122). It should be noted that a variety of transition metals, such as Au(I), Au(III), Cu(I), Pt(II), and Pd(II), were shown to catalyze this transformation with variable degrees of efficiency. 

The hydroboration of disubstituted (internal) alkynes leads to a mixture of two ketones. When 2-pentyne reacts with borane, two vinylboranes are formed in virtually equal amounts 120 and 121. There is no significant difference in steric hindrance to make one transition state favored over the other, so both vinylboranes are formed. Subsequent oxidation leads to the isomeric ketone products (from their respective enols) 2-pentanone (122) and 3-pentanone H23). To conclude, hydroboration of a terminal alkyne leads to an aldehyde as the major product, whereas hydroboration of an internal alkyne gives a mixture of two isomeric ketones. 

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