General reactivity intermolecular cycloadditions

In addition to siloxy- and alkoxy-substituted VCPs, alkyl- and H-substituted VCPs are also effective in the intermolecular [5 + 2]-cycloaddition reaction (Scheme 11). In general, an increase in the steric bulk of the cyclopropane substituent (H vs. Me vs. Pr1) leads to increased reaction rates, putatively through preferential population of the more reactive as-oid arrangement of the vinyl and cyclopropane moieties.43... 

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. 

Generally, the notable features of intramolecular cycloadditions are 1) the success of the intramolecular reaction between carbonyl and alkene moieties compared lo other intramolecular events, and 2) the enhanced reactivity of linked addends relative to an intermolecular equivalent60. The latter can be illustrated by the intramolecular reaction of 5-hepten-2-one to give a cyclobuta-subsLituted oxetane55 acetone singlet and 2-butene do not react. 

Intermolecular and intramolecular [3+2] cycloaddition reactions are among the most efficient and tvidely used procedures for synthesis of five-membered heterocycles. The reactive partners in these reactions are 1,3-dipoles and dipolarophiles such as alkenes and alkynes. 1,3-Dipoles vary in stability some can be isolated and stored, others are relatively stable, but they are usually employed immediately. Others are so unstable that they have to be generated and reacted in situ. There are tv ro general classes of dipole, often referred to as sp (Fig. 11.1) and sp -hybridized dipoles (Fig. 11.2). 

Selective intermolecular [2 - - 2 - - 2] cycloaddition of terminal alkynes is more difficult to achieve than internal alkynes, due to their various reactivities toward transition-metal complexes in addition to the regioselectivity problem. Indeed, a neutral rhodium(I)/phosphine complex such as RhCl(PPh3)3 generally reacts with terminal alkynes to give not cyclotrimers but linear dimers [20]. The neutral rhodium(I) and rhodium(III) complexes could be applied to intermolecular [2 - - 2 - - 2] cycloaddition of terminal alkynes (Scheme 4.5) [13,15a and b]. 

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