Pauson-Khand reaction enynes

Cascade Synthesis of Enynes/Pauson-Khand Reaction. 221... 

RCM of 132 to the medium-sized enyne 135, for example, appears to be highly unlikely. This transformation was achieved by conversion of 132 to the cobalt complex 133, which is cyclized to the protected cycloenyne 134. Deprotection yields 135, and a subsequent Pauson-Khand reaction yields the interesting tricyclic structure 136 (Scheme 27) [125c]. 

Rh(III)-metallocydes derived from 1,6-enynes are postulated as reactive intermediates in catalytic [4+2] and [5+2] cycloadditions, Pauson-Khand reactions and cycloisomerizations P. Cao, B. Wang, X. Zhang, J. Am. Chem. Soc. 2000, 122, 64901 and references cited therein. 

The sequential double migratory insertion of CO into acydic and cydic diorganozircono-cene complexes through acylzirconocene and ketone—zirconocene species provides a convenient procedure for preparing acyclic and cyclic ketones (Scheme 5.6) [8], Thus, the bi-cydic enones from enynes can be obtained through CO insertion into zirconacyclopen-tenes followed by a subsequent rearrangement (Scheme 5.7). The scope and limitations of this procedure have been described in detail elsewhere [8d]. This procedure provides a complementary version of the well-known Pauson Khand reaction [9]. 

An important advance was reported by Schore and Croudace [13], who showed for the first time that carbon-tethered enyne precursors undergo an intramolecular Pauson-Khand reaction (PKR) in good yields with complete control of regioselectivity. In this connection, it was not essential to use strained olefins as starting materials. 

Some of the most striking examples for an intramolecular Pauson-Khand reaction involving a tetrasubstituted double bond are the cobalt-mediated cyc-lizations of bicyclopropylidene derivatives 234 leading to the interesting spirocyclopropanated tricyclic products 235. The successful cyclizations even of the trimethylsilyl-substituted enynes 234 demonstrate the unique reactivity of the strained double bond in the bicyclopropylidene moiety of these molecules (Scheme 55) [145]. 

In sharp contrast to the unique pattern for the incorporation of carbon monoxide into the 1,6-diyne 63, aldehyde 77 was obtained as the sole product in the rhodium-catalyzed reaction of 1,6-enyne 76 with a molar equivalent of Me2PhSiH under CO (Scheme 6.15, mode 1) [22]. This result can be explained by the stepwise insertion of the acetylenic and vinylic moieties into the Rh-Si bond, the formyl group being generated by the reductive elimination to afford 77. The fact that a formyl group can be introduced to the ole-finic moiety of 76 under mild conditions should be stressed, since enoxysilanes are isolated in the rhodium-catalyzed silylformylation of simple alkenes under forcing conditions. The 1,6-enyne 76 is used as a typical model for Pauson-Khand reactions (Scheme 6.15, mode 2) [23], whereas formation of the corresponding product was completely suppressed in the presence of a hydrosilane. The selective formation of 79 in the absence of CO (Scheme 6.15, mode 3) supports the stepwise insertion of the acetylenic and olefmic moieties in the same molecules into the Rh-Si bond. 

Application of the intramolecular Pauson-Khand reaction to enynes derived from salicylaldehyde leads to the cyclopentenone 27 (Scheme 13) <99TL2817>. Intramolecular Diels-Alder reactions feature in syntheses of the bipyridyl 28 <99CC793> and benzopyrano[4,3-b]quinolines <99JCR254>. 

When this reaction is carried out under 1 atm of nitrogen or GO atmosphere, a cyclopentane 276 is formed selectively in a minute at 25 °G (Scheme 13, mode 2). Although the Pauson-Khand reaction of 1,6-enyne 273 (Scheme 13, mode 3) gives 21H, this transformation is completely suppressed under the conditions of mode 1. Even simple alkyne silylformylation product 277 is not detected at all. This contrasts sharply to the silylformylation of l-penten-4-yne 48 carried out under similar conditions (Equation (12)). These results can be explained by a pathway similar to the reaction of 1,6-diynes (i) stepwise insertion of the acetylenic and olefmic moieties into the Rh-Si bond in this order, and (ii) subsequent interaction of GO and Mc2PhSiH with the resultant intermediate to give 275. The... 

Intramolecular Pauson-Khand reactions to prepare [3.3.0]-bicyclo-octenones from several 1,6-enynes (eq. 2.11) were reported to occur efficiently in sc C02 using a Co2(CO)8 catalyst (Jeong et ah, 1997). The reactions proceed very well regardless of the substitution pattern of... 

A further addition-cyclization process that leads to complex fused-ring systems is the dicobalt octacarbonyl-mediated Pauson-Khand reaction which, applied to enynes 209 and 211, gives respectively and in modest yields the tricyclic cyclopentenones 210215 and 212.216... 

Insertion of CO to the metallacyclopentenes 197 and 198 formed from enynes and metal complexes offers a useful synthetic route to the cyclopentenone derivatives 199 and 200. This [2+2+1] cycloaddition mediated by Co2(CO)8 is called the Pauson-Khand reaction [80], Both inter- and intramolecular versions are known. 

The Pauson-Khand reaction, promoted by (CO)3Mo(DMF)3, has been found to take place under very mild conditions in the absence of any promoter. High yields of the adducts were obtained in the cyclization of a wide variety of functionalized 1,6- and 1,7-enynes. Enynes bearing electron-withdrawing groups at the alkene terminus proved to be particularly good substrates.121 The exclusive formation of cyclopentenones was observed in the molybdenum hexacarbonyl (10 mol%)-catalysed Pauson-Khand reactions of 1,6-allenynes under 1 atm of CO (balloon) in excellent yields.122... 

When enyne cycloisomerization takes place in the presence of an unsaturated molecule an insertion reaction can occur. Thus, Ru3(CO)12 catalyzes the cycloisomerization of 1,6-enynes under a CO atmosphere to give an insertion of carbon monoxide and the formation of bicyclic cyclopentenones as a catalytic Pauson-Khand reaction [78] (Eq. 57). 

In terms of functional group compatibility, ethers, alcohols, tertiary amines, acetals, esters, amides and heterocycles are compatible with the Pauson-Khand reaction. In the intramolecular version, relatively few carbon skeletons undergo the cyclization. Most intramolecular PKRs use systems derived from hept-l-en-6-yne (6) or propargyl allyl ethers (7) or amines (8). Other interesting and more recent substrates are enynes connected through aromatic rings like 9-11, which have allowed us and other groups to obtain aromatic polycycles (Fig. 1) [28-31]. 

There is only one example of a catalytic Pauson-Khand reaction in an ionic liquid1471 although the reaction has also been conducted in ionic liquids using stoichiometric amounts of Co2(CO)8/481 In the catalysed reaction 10 mol% of Co2(CO)8 was used in [C4Ciim][PF6] under 10 bar of CO. Under these conditions, diethylallyl malonates could be obtained in 90-99% yield within 90 minutes at 80°C, as shown in Scheme 9.14. However, with hetero-bridged enynes, as well as in the reaction between norbomene and phenylacetylene, only poor to moderate yields were achieved. A slight increase in activity was observed with the analogous tetrafluoroborate ionic liquid. 

Pd-cat = [Pd(PPhg)2(OAc)2] cycloisomerization Ru-cat I = Hoveyda-Qrubbs II Enyne metathesis Ru-cat II = [CpRu(CHgCN)gPFg] cydoisomerization ([5 + 2]-reactlon) Au-cat= NaAuCI cydoketaiization [COg(CO)g] Pauson-Khand reaction NaH lactonization... 

Intramolecular Pauson Khand reactions are synthetically more useful compared to their intermolecular counterparts. Enynes separated by either three or four atoms (1,6- or 1,7-enynes) cyclize in an intramolecular fashion upon complexa-tion with Co2(CO)s, and subsequent heating to form bicycUc enones. Angular tricyclic ring systems have been prepared in... 

Prior to the development of enyne bicyclization reactions promoted by Zr and other Group IV metals, the Co-catalyzed enyne bicyclization-carbonylation reaction (the Pauson-Khand reaction ) was known. This reaction is discussed in Volume 5, Chapter 9.1. In the Pauson-Khand reaction, the overall transformation is the conversion of enynes into bicyclic enones, and the organometallic bicyclic intermediates are usually neither readily available nor isolated. The use of Co2(CO)s, an 18-electron species, necessitates relatively high reaction temperatures. These and other limitations suggested the desirability of developing alternative enyne bicyclization reactions. 

---