Reductive elimination alkyne derivatives

Although much less prevalent than the use of CO in lactone synthesis, direct incorporation of CO2 for the synthesis of lactones is advantageous due to lower toxicity while maintaining high atom efficiency. Louie and coworkers demonstrated that a formal [2 + 2 + 2] cycloaddition of bis-alkynes with CO2 yields pyrone derivatives under Ni(0) catalysis (Scheme 2.62) [117]. It is proposed that an initial cydometallation of one alkyne and CO2 yields a Ni(II) metallacycle, followed by insertion of the other alkyne and reductive elimination. Pd(0) has also demonstrated catalytic activity in carboxylations of methoxyallene [118] and 1,3-butadiene [119]. 

The insertion of alkynes into a chromium-carbon double bond is not restricted to Fischer alkenylcarbene complexes. Numerous transformations of this kind have been performed with simple alkylcarbene complexes, from which unstable a,/J-unsaturated carbene complexes were formed in situ, and in turn underwent further reactions in several different ways. For example, reaction of the 1-me-thoxyethylidene complex 6a with the conjugated enyne-ketimines and -ketones 131 afforded pyrrole [92] and furan 134 derivatives [93], respectively. The alkyne-inserted intermediate 132 apparently undergoes 671-electrocyclization and reductive elimination to afford enol ether 133, which yields the cycloaddition product 134 via a subsequent hydrolysis (Scheme 28). This transformation also demonstrates that Fischer carbene complexes are highly selective in their reactivity toward alkynes in the presence of other multiple bonds (Table 6). 

The regioselectivity observed in these reactions can be correlated with the resonance structure shown in Fig. 2. The reaction with electron-rich or electron-poor alkynes leads to intermediates which are the expected on the basis of polarity matching. In Fig. 2 is represented the reaction with an ynone leading to a metalacycle intermediate (formal [4C+2S] cycloadduct) which produces the final products after a reductive elimination and subsequent isomerisation. Also, these reactions can proceed under photochemical conditions. Thus, Campos, Rodriguez et al. reported the cycloaddition reactions of iminocarbene complexes and alkynes [57,58], alkenes [57] and heteroatom-containing double bonds to give 2Ff-pyrrole, 1-pyrroline and triazoline derivatives, respectively [59]. 

Based on his previous work on the catalytic double addition of diazo compounds to alkynes173 using Cp RuCl(COD),174 Dixneuf has developed an efficient one-step synthesis of alkenyl bicyclo[3.1.0]-hexane derivatives of type 163 from enyne precursors 162 (Scheme 43). The catalytic cycle starts with the formation of an Ru=CHR species. It then adds to an alkyne to form ruthenacyclobutene 166, which evolves into vinylcarbene 167. [2 + 2]-Cycloaddition of 167 gives ruthenacyclobutane 168. The novelty in this transformation is the subsequent reductive elimination to give 170 without leading to the formation of diene 169. This can be attributed to the steric hindrance of the CsMes-Ru group. 

To probe the reaction mechanism of the silane-mediated reaction, EtjSiD was substituted for PMHS in the cyclization of 1,6-enyne 34a.5 The mono-deuterated reductive cyclization product 34b was obtained as a single diastereomer. This result is consistent with entry of palladium into the catalytic cycle as the hydride derived from its reaction with acetic acid. Alkyne hydrometallation provides intermediate A-7, which upon cw-carbopalladation gives rise to cyclic intermediate B-6. Delivery of deuterium to the palladium center provides C-2, which upon reductive elimination provides the mono-deuterated product 34b, along with palladium(O) to close the catalytic cycle. The relative stereochemistry of 34b was not determined but was inferred on the basis of the aforementioned mechanism (Scheme 24). 

Disubstituted silole derivatives are synthesized by the palladium-catalyzed reaction of (trialkylstannyl)di-methylsilane with terminal alkynes (Equation (107)).266 The mechanism is supposed to involve a palladium silylene complex, which is generated via /3-hydride elimination from LJ3d(SiMe2H)(SnBu3) (Scheme 62). Successive incorporation of two alkyne molecules into the complex followed by reductive elimination gives rise to the silole products. 

In comparison with the hydroboration and diborafion reactions, thioboration reactions are relatively limited. In 1993, Suzuki and co-workers reported the Pd(0)-catalyzed addition of 9-(alkylthio)-9-BBN (BBN = borabicyclo [3.3.1] nonane) derivatives to terminal alkynes to produce (alkylthio)boranes, which are known as versatile reagents to introduce alkylthio groups into organic molecules [21], Experimental results indicate that the thioboration reactions, specific to terminal alkynes, are preferentially catalyzed by Pd(0) complexes, e.g. Pd(PPh3)4, producing (thioboryl)alkene products, in which the Z-isomers are dominant. A mechanism proposed by Suzuki and co-workers for the reactions involves an oxidative addition of the B-S bond to the Pd(0) complex, the insertion of an alkyne into the Pd-B or Pd-S bond, and the reductive elimination of the (thioboryl)alkene product. 

Carbocupration of alkynes by zirconacyclopentane derivatives can be performed according to the same procedure. Thus, the zirconocyclopentane 135, obtained by treatment of Bu2ZrCp2 with 1,6-heptadiene, reacts at room temperature with phe-nylacetylene to afford the adduct 136 through a carbocupration-reductive elimination mechanism. Cross-coupling followed by intramolecular carbocupration takes place in the case of the reaction with 1-bromohexyne, producing 137 (Scheme 2.66) [143]. 

As a related reaction, the bicyclo[5.3.0]decane derivative 64 was obtained at 30 °C by the Rh-catalysed intramolecular [5+2] cycloaddition of the alkyne with the vinylcyclopropane moiety in 61. The latter behaves as a pseudo-1,3-diene in oxidative addition, and generates 62. This is followed by rearrangement to 63, whose reductive elimination gives 64 [20]. [Rh(CO)2Cl]2 is a better catalyst than RhCUPl+P. The reaction can be extended to alkenes [20a],... 

The reactions of type II proceed by transmetallation of the complex 5. The transmetallation of 5 with hard carbon nucleophiles M R (M = main group metals) such as Grignard reagents and metal hydrides MH generates 8. Subsequent reductive elimination gives rise to an allene derivative as the final product. Coupling reactions of terminal alkynes in the presence of Cul belong to Type II. 

Benzene and cyclooctatetraene (COT) derivatives are formed by [2+2+2] and [2+2+2+2] cycloadditions of alkynes. At first the metallacyclopropene 107 and metallacyclopentadiene 108 are formed. Benzene and COT (106) are formed by reductive elimination of the metallacycloheptatriene 109 and the metallacyclononate-traene 110. Formation of benzene by the [2+2+2] cycloaddition of acetylene is catalysed by several transition metals. Synthesis of benzene derivatives from... 

Related complexes of group 10 metals are accessible by an oxidative addition/reductive cyclization protocol, exploiting the inverse electron demand (Scheme 27) (Pt <2005JA13494>, Ni <20030M3604>). The nickel complex is thermally unstable, proceeding to perylene via a bimolecular reductive elimination or, in the presence of alkynes, delivering acenaphthylene derivatives by an insertion/reductive elimination pathway. 

One of the first examples of ruthenium-catalyzed C-C bond formation afforded the synthesis of cyclobutenes, from norbornene derivatives with dimethyl acetylenedicarboxylate, and was reported by Mitsudo and coworkers [45, 46] by using various catalysts such as RuH2(CO)[P(p-C6H4F)3]3 or RuH2(PPh3)4. More recently, the complex Cp RuCl(COD) has shown to be an excellent catalyst for the [2+2] cycloaddition of norbornenes with various internal alkynes [45] (Eq. 33) and with a variety of substituted norbornenes and norbornadienes [47]. The ruthenacycle intermediate, formed by oxidative coupling, cannot undergo /1-hydride elimination and leads to cyclobutene via a reductive elimination. 

Pd species. This intermediate undergoes carbonylation, methoxy substitution, and reductive elimination to furnish the Z-configured derivative 193. The resulting Pd(0)-species is reoxidized by oxygen in the presence of iodide ions. On the other hand, the presence of potassium iodide can also equilibrate the ( 2-alkynyl carbamate-Pd-iodide complex to the r/2-alkynyl carbamate-Pd-diiodide complex, which, in turn, causes an anti-attack of the carbamate at the Pdl2-complexed alkyne. Therefore, an antz-vinyl-Pd species results, which ultimately and accordingly leads to the -configured derivative 194. Without carbon monoxide the vinyl-Pd-species suffer a hydro-demetallation. 

Chalk and Harrod provided the first mechanistic explanation for the transition metal catalyzed hydrosilation as early as in 1965. Their mechanism was derived from studies with Speier s catalyst and provided a general scheme, which could be used also for other transition metals. The catalytic cycle consists of an initial oxidative addition (see Oxidative Addition) of the Si-H bond, followed by coordination of the unsaturated molecule, a subsequent migratory insertion (see Insertion) into the metal-hydride bond and eventually a reductive elimination (see Reductive Elimination) (Scheme 3 lower cycle). The scheme provides an explanation for the observed Z-geometry in the hydrosilation of alkynes, which is a consequence of the syn-addition mechanism. The observation of silated alkenes as by-products in the hydrosilation of alkenes along with the lack of well-established stoichiometric examples of reductive elimination of aUcylsilanes from alkyl silyl metal complexes... 

Addition of an alkene insertion step to the sequence above prior to reductive elimination of the final product gives an alkene-derived R group. Although for reliable results the reaction is restricted to ethylene, giving an ethyl substituent at C-4, yields and alkyne regioselectivity are reasonable (equation 14)P... 

A wide variety of homogeneous and heterogeneous catalysts are available for alkyne cyclotrimerization. As a result, numerous mechanistic pathways have been established for the different versions of this process, each characteristic of the metals involved in the system. The most common involves the intermediacy of metallacyclopentadienes, derived as already shown from any number of metal fragments and two alkynes. Upon opening a vacant coordination site, these systems may readily complex a third alkyne, which may insert to give a transient metallacycloheptatriene from which the benzene product is ultimately released via reductive elimination of the metal (Scheme 24). ... 

Oxanickelacyclopentenones (87) react in many different ways. With carbon monoxide, derivatives of 94 are formed.Insertion of an alkyne leads to the ring-expanded seven-membered oxanickelacycloheptadienones 96, which on hydrolysis yield oxacyclopentenones (99) or dienes (98). Reductive elimination of the organic substrate from 96 is also observed to give... 

A connective synthesis of alkynes inspired by the Julia alkenation was developed by Lythgoe and coworkers for the synthesis of la-hydroxy vitamin D3, as shown in Scheme 34. The P-keto sulfone (101) derived by condensation of the the metalated sulfone (99) with the ester (100) was converted to the enol phosphate (102), which on reductive elimination gave the enynene (103). 

Intermediate 2 can coordinate an additional alkyne (or olefin) to give 5 after insertion into the Ni-C bond (Scheme 7). Reductive elimination affords the corresponding cyclodecatriene derivative. Several related stoichiometric reactions with certain Ni complexes and alkynes or allene have been observed, thus confirming the proposed catalytic cycle (route ( )) [48] (eqs. (17) and (18)). 

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