Pauson bicyclo derivatives

Sufficient information about the reaction has been gathered to allow fairly accurate predictions of yield as well as of stereo- and regioselectivity.176177 The reaction proceeds via the formation of hexacarbonylalkyne-dicobalt complexes and is remarkably tolerant of functional groups in both the alkyne and the alkene. The intramolecular Pauson-Khand reaction is an effective way of preparing bi- and polycyclic systems, and the cyclization of 1,6-heptenyne derivatives to give bicyclo[3.3.0]oct-l-en-3-ones has been the most popular application of the Pauson-Khand reaction in natural product synthesis [Eq. (17)]. 

Enynes in which three or four atoms separate the double and triple bonds cyclize upon complexation to Co2(CO)g and subsequent heating to give bicyclic enones (equation 52). With the exception of slightly elevated temperatures the conditions required are no different than those of the stoichiometric procedure described earlier for reactive substrates in intermolecular Pauson-Khand reactions. The intramolecular cycloaddition cannot in general be carried out under catalytic conditions. Hex-l-en-5-yne, which would give a four-membered ring upon intramolecular cycloaddition, instead undergoes alkyne trimerization exclusively.3 The most extensively studied systems are those derived from hept-l-en-6-yne, as the products, bicyclo[3.3.0]oct-l-en-3-ones, are useful in the synthesis of numerous cyclopentane-based polycy-clics. 

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]. 

Tethering the ene and yne reaction partners for Pauson-Khand cycloaddition was first conceived as a way to improve simultaneously the effective reactivity of simple alkene moieties and to provide access to a wider variety of bi- and polycyclic systems. Indeed, well over 100 examples of such cycloadditions have been published, mostly involving reactions of derivatives of 1,6-heptenyne to give bicyclo[3.3.0]oct-l-en-3-ones [cf. Eq. (37)] together with a smaller number of 1,7-octenynes, which afford bicyclo[4.3.0]non-l (9)-en-8-ones [81 c, 117]. The use of dry-state conditions [118] or additives such as amine oxides [119] has virtually revolutionized this field the cycloaddition shown in Eq. (52) is completed in 15 minutes( ) when promoted by NMO. 

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