Reductive cyclization of enyne

The reductive cyclization of enynes has been used to prepare exo-methylene-cycloalkanes. Two systems have proven successful in this transformation, namely PMHS/Pd2(dba)3 CHCl3245 (Eq. 102) and Et3SiH/Pd(dppe)Cl2/HC02H (Eq. 103).246... 

The first rhodium-catalyzed reductive cyclization of enynes was reported in I992.61,61a As demonstrated by the cyclization of 1,6-enyne 37a to vinylsilane 37b, the rhodium-catalyzed reaction is a hydrosilylative transformation and, hence, complements its palladium-catalyzed counterpart, which is a formal hydrogenative process mediated by silane. Following this seminal report, improved catalyst systems were developed enabling cyclization at progressively lower temperatures and shorter reaction times. For example, it was found that A-heterocyclic carbene complexes of rhodium catalyze the reaction at 40°C,62 and through the use of immobilized cobalt-rhodium bimetallic nanoparticle catalysts, the hydrosilylative cyclization proceeds at ambient temperature.6... 

This chapter is intended to highlight recent results in the fields of intra- and intermolecular carbometallation, but we will concentrate only on the chemistry of lithium and zinc derivatives. Although the Group IV metallocene-mediated reductive cyclizations of enynes [36] and dienes [36], and the use of transition metals of Group VIII, as well as the more recent development of the organolanthanide chemistry [37] followed by selective reaction with different electrophiles [36], represent an important methodology for the construction of polysubstituted carbocycles, they will not be addressed here. 

The reductive cyclization of enynes has been successfully applied to the synthesis of /i-nccrodol... 

Several reports have dealt with the reductive cyclization of enynes where the alkyne component undergoes addition to an adjacent carbonyl group. Typical of this is irradiation of 155, in the presence of the SET sensitizer trie thy lamine, which affords the bicyclic product 156, a piperidone, that was used in a synthesis of z o-oxyskyanthine. Unsaturated aldehydes such as 157 also undergo this photo-electron transfer-induced cyclization to afford a mixture of alcohols 158 (Scheme 6) . Pete and his coworkers have extended their study of this reductive cyclization of unsaturated ketones in a synthesis of hirsutene 159. The reaction involves the irradiation of the ketone 160 at 254 nm in the presence of triethylamine, whereby the tricyclic compound 161 is formed in 58% yield. This is subsequently transformed into hirsutene ... 

Palladiiun complexes are effective catalysts for the reductive cyclization of enyne substrates [53,54]. The first report of catalytic cyclization of 1,6- and 1,7-enynes 115a,b to cyclopentane 116a and cyclohexane 116b derivatives appeared in 1987 (Eq. 19) [70]. The authors proposed that the Pd(II) species 117 forms by oxidative addition of acetic acid to Pd(0) (Scheme 25). Complex 117 hydrometallates the aUcyne to give 118, which cycUzes to provide... 

Similar reactivity is observed in the cyclization of enynes in the presence of the yttrium-based catalyst 70 and a silane reductant [53,54]. The 1,6- and 1,7-enynes 90 and 91 provide -E-alkylidene-cyclopentancs 92 and -cyclohexanes 93 in very good yield (Eq. 15, Scheme 20) [55]. These transformations likely proceed by syn hydrometallation of the 7r-basic alkyne, followed by insertion of the alkene and a-bond metathesis. The reaction of 1,6-enynes tolerated... 

Rhodium and rhodium-cobalt based catalysts using silanes as the stoichiometric reductant were initially reported in 1992 to reductively couple enyne substrate (Eq. 30) [90,91]. Further investigation showed this reaction to be an effective method for the cyclization of enyne substrates 129 to... 

Few other examples of such reaction sequences have been described to date. Oh has reported the palladium-catalyzed reductive cyclizations of 1,6-enynes in the presence of formic acid or triethylsilane via an alkylpalladium intermediate and its application to organic synthesis. Palladium complexes also catalyze the conversion of a range of enynes to cyclic 6,7-unsaturated carboxylic acids in the presence of CO.260... 

The products of reductive cyclization incorporate two non-exchangeable hydrogen atoms. Homolytic and heterolytic hydrogen activation pathways may now be discriminated on the basis of hydrogen-deuterium crossover experiments. Reductive cyclization of the indicated nitrogen-tethered enyne under a mixed atmosphere... 

Table 22.11 Reductive cyclization of assorted 1,6-diynes and 1,6-enynes.

The precursor of (+ )-anthramycin, pyrrolo-benzodiazepine 196, can be synthesized by deprotection, acylation and reductive cyclization of pyrrolidine derivative 195, obtained by enyne metathesis (Scheme 40 (2004T9649)). 

Trost and Tanoury found an interesting skeletal reorganization of enynes using a palladium catalyst.In this reaction, the second product is derived from a metathesis reaction (Equation (5)). It was speculated that the reaction would proceed by oxidative cyclization of enynes with the palladium complex followed by reductive elimination and then ring opening. To confirm this reaction mechanism, they obtained a compound having a cyclobutene ring, which was considered to be formed by the reductive elimination (Equation (6)). 

Reductive Cyclization of 1,6- and 1,7-Dienes, Diynes, Enynes and Arenes via Zirconacycles and Titanacycles... 

Another reaction is reductive cyclization of 1,6-diynes and 1,6-enynes using hydrosilanes as a hydrogen source in AcOH. Triethylsilane is used as the hydrogen donor for this reaction [142], The reaction can be understood by the formation of vinylpalladium bond 350 via the insertion of alkyne 349 to the Pd—H bond in 328. Then intramolecular alkyne insertion gives vinylpalladium 351, which is hydro-genolysed with Si—H to give the 1,3-diene 352 by transmetallation and reductive... 

Reductive cyclizations. Substituted pyrrolidines and piperidines are obtained by the Ti(Il)-mediated cyclization of enyne carbonates. 5-Ketoesters and ketonitriles undergo radical cyclization with CpjTiPh which is obtained as a dark green solution by sequential treatment of Cp TiClj with i-PrMgCl and PhMgBr. 

Table 2-10. Rh-catalyzed reductive cyclization of 1,6 enynes mediated by hydrogen.

Reductive cyclization of diynes or enynes was catalyzed by NHC-Pt complexes in the presence of H2 and SnCl2 as activator (Equation (10.33)) to afford an interesting pathway to 2,5-dihydrofurans, pyrroles or cyclopentenes in moderate to good yields (50-88%). ° ... 

---