Pauson-Khand reaction tandem

Aminocarbonylation has been combined with the Pauson-Khand reaction to construct fused tricyclic alkaloid skeletons (see 00154). The tandem aminocarbonylation/Pauson-Khand reaction of haloalkynes with a chiral allylic amine promoted by Co2(CO)8 gave angular triquinanes as exemplified in Scheme 25. Thus, the reaction of l-chloro-2-phenylethyne 175 with Co2(CO)8 at 0°C gave alkyne-dicobalt complex 176, which was converted to enoyl-dicobalt complex 177 upon warming to 25 °C. The reaction of enoyl-dicobalt complex 177 with cyclopente-nylmethyl(l-phenylethyl)amine 179 yielded Pauson-Khand reaction product, angular triquinane 180, via A -allylic aminocarbonylated alkyne-dicobalt complex 178 (Scheme 25). ... 

This tandem reaction is believed to proceed via Pauson-Khand reaction between the diyne and carbon monoxide to give an intermediate bicyclopen-tadienone. 

In the laboratory of S.L. Schreiber, the total synthesis of (+)-epoxydictymene was accomplished by the tandem use of cobalt-mediated reactions as key steps. The eight-membered carbocycle was formed via a Nicholas reaction, while the five-membered ring was annulated by the Pauson-Khand reaction. Several P.-K. conditions were explored and the best diastereoselectivity was observed when NMO was used as a promoter. The annulated product was isolated as an 11 1 mixture of diastereomers. 

Note added in proof Compound 99 has recently been approached by a tandem Pauson-Khand reaction Van Ornum SG, Cook JH (1998) ACS Spring meeting, Dallas. 

Jeong et al. demonstrated that the tandem allylic alkylation/Pauson—Khand reaction of the propargylic amines 96 with allyl acetate 97 and CO took place in the presence of a mixture of palladium and rhodium catalysts to give the bicyclopentenones 98 in high yields (Scheme 33).112 Most probably, the allylation of 96 with allyl acetate 97 occurs in the presence of palladium catalyst to give the corresponding enyne, which undergoes the Pauson—... 

Tandem Nucleophilic Coupling/Pauson-Khand Reaction... 

Few other qfdoaddition reactions with microwave irradiation have appeared in the literature since the first applications were published. In particular, the [2+2+1] reaction, known as the Pauson-Khand reaction, [6+4], and tandem [6+4]-[4+2] cycloadditions have been reported as being performed successfully under micro-wave conditions. A range of examples is described below. 

Complementary to the hetero-Pauson-Khand reaction (see Section 2.2.6), [2 + 2] cydoaddition of ketenes and aldehydes provides rapid access to P-lactones from relatively simple starting materials. Cationic [Pd(dppb)(CH3CN)2]Bp4 was selected as the optimal catalyst (Scheme 2.64) (122,123]. A tandem allylic rearrangement/ring expansion sequence was also developed that provides elaboration of P-lactones to 3,6-dihydro-2H-pyran-2-ones in a one-pot process (Scheme 2.65) [123]. 

Alkenyl-l-alkynylcyclopropane 33 underwent rhodium-catalyzed tandem Pauson-Khand reaction/spiropentane carbonylation to give 6-hydroxy-l-indanone 34 (Scheme 2.30) [46]. 

Scheme 2.30 Tandem Pauson-Khand reaction/spiropentane carbonylation.

The most impressive use of a tandem strategy involving the Nicholas reaction in a total synthesis project is Schreiber s preparation of (+)-epoxydict5miene (61). Cobalt complexation of 58 followed by an endocyclic intramolecular Nicholas reaction with an allylsilane nucleophile yields Pauson-Khand precursor 59. Treatment of 59 with iV-methylmorpholine-iV-oxide (NMO) promotes the Pauson-Khand reaction to furnish tetracycle 60 which was ultimately converted to the target natural product 61. ... 

In connection with the aforementioned reaction, Shea et al. reported the synthesis of [5,8,5]- and [5,7,5]-tricyclic oxygen-containing heterocycles via tandem Nicholas [35] and Pauson-Khand [23,24] reactions of acyclic enynes [36]. A typical Nicholas/[2 + 2 + 1] sequence is depicted in Scheme 12. 

However, in another contribution, Chung and coworkers realized the one-pot synthesis of [ S.5.5.6] fenestranes 42 via intramolecular cobalt-catalyzed tandem Pauson-Khand/Diels-Alder reactions of dienediynes 41 [44] (Scheme 21). 

It is also worthy of note that the construction of tetracyclic compounds 44 by cobalt-catalyzed tandem Pauson-Khand/[2 + 2 + 2] cycloaddition reactions of 1,6-diynes 43 was also reported by Chung et al. [45,46]. It was experimentally shown that the [2 + 2 + 2] cycloaddition reaction occurs after the [2 + 2 + 1] cycloaddition between CO and the substrate (Scheme 22). 

An additional advantage of the intramolecular protocol stems from the opportunity to prepare easily the required polyfunctional precursors via cobalt carbonyl stabilized propargyl cations. The approach based on the tandem utilization of Co-mediated alkylation and Pauson-Khand annulation was developed in Schreiber s studies to elaborate short pathways for the synthesis of polycyclic compounds. An example of the efficiency of this protocol is the two-step transformation of the acyclic precursor 409 into the tricyclic derivative 410. The cobalt-complexed acetal 409 was first transformed into the cyclooctyne derivative 411 via intramolecular reaction of the in situ generated propargyl cation 409a with the allylsilane moiety. Cyclooctyne 411 underwent smooth cycloaddition in the presence of carbon monoxide to give the target compound 410 with excellent stereoselectivity. 

Khand reaction with CO in the presence of rhodium catalyst. Evans and Robinson reported that the regio-and diastereoselective tandem allylic alkylation/ Pauson-Khand annulation reaction of the propargylic derivatives 99 with the allylic carbonate 100 and CO took place in the presence of a rhodium catalyst only (Scheme 34).113... 

In concluding this section on the reactions of propargylium complexes with nucleophiles, we note that use of appropriate unsaturated nucleophiles as reaction partners with the cobalt cations or unsaturated electrophiles in the Ade reaction of Co-compleced 1,3-enynes [213-215] offers an efficient route to variously substituted a,(i)-enynes, valuable precursors for intramolecular Pauson-Khand cyclizations (Scheme 4-64) [96, 98]. This tandem methodology has been employed to produce, among others, bicyclo[3.3.0]octenones and their 3-oxa analogs [22, 216, 217], the fusicoccin sesquiterpenoid skeleton [218], linear and angular fused tri- and tetracyclics [219], and fenestrane derivatives [220]. 

Shi and co-workers reported a Pauson-Khand type [3+2+1] cycloaddition reaction of ene-vinylidenecyclopropanes and CO in the presence of rhodium(I) catalyst [122]. Both cyclic and noncyclic substituent could be tolerated (see (48)). Shi also reported a tandem process that craiverted 1,4-enynes tethered by cyclopropyl group... 

When the reaction conditions were applied to allylic carbonate 8, the palladium-mediated cyclization occurred to form the 11-membered ketone 9 in 86% yield (eq 30). When the palladiun-catalyzed allylation of propargyl malonate 10 in the presence of BSA was combined with the rhodium-catalyzed Pauson-Khand t)fpe reaction, the tandem action of the two catalysts gave an excellent yield (92%) of bicyclopentenone 11 in one-pot (eq 31). ... 

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