General reactivity intramolecular cycloadditions

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. 

Electrocyclization of 1,4-dienes is an efficient process when a heteroatom with a lone pair of electrons is placed in the 3-position, as in 77 (Scheme 20)38. Photoexcitation of these systems generally results in efficient formation of a C—C bond via 6e conrotatory cyclization to afford the ylide 78. These reactive intermediates can undergo a variety of processes, including H-transfer (via a suprafacial 1,4-H transfer) to 79 or oxidation to 80. In a spectacular example of reaction, and the potential it holds for complex molecule synthesis, Dittami and coworkers found that the zwitterion formed by photolysis of divinyl ether 81 could be efficiently trapped in an intramolecular [3 + 2] cycloaddition by the... 

Cyclopropanes exhibit similar modes of reactivity. [2Dipolar additions with electron-deficient alkenes and electron-donor-substituted cyclopropanes, additions of electron-rich alkenes to electron-deficient cyclopropanes, a number of radicaloid reactions and intramolecular photochemical cycloadditions are known, which may be described by the general scheme H-2 3. 

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). 

A domino sequence comprising a cycloaddition and subsequent cycloreversion step can often find a more general application in organic synthesis, especially in the formation of aromatic compounds such as furans or pyrroles. Oxazole moieties as electron-deficient dienes often serve as the crucial reactive centers which cycloadd to a triple bond and eliminate a nitrile upon cycloreversion. If the first step is intramolecular, the impelling enthalpy preserved in the stability of the formed CN function is additionally accompanied by a positive entropy when the nitrile, sometimes volatile, leaves the substrate. In an older example from 1984 [10], Jacobi and coworkers devised a scheme for the preparation of a highly substituted furan on their synthetic way to paniculide A. An intramolecular Diels-Alder reaction was followed by the critical extrusion of volatile acetonitrile, furnishing the bicycle 8 in 94% yield (Scheme 6.2). 

Subsequent investigations revealed that the corresponding hexafluoroanti-monate complex 166 generally possessed higher reactivity and resulted in improved stereoselectivity in such cycloadditions [89]. In all cases, the observed induction could be explained in terms of a catalyst-substrate model complex as depicted for 163 with a distorted tetrahedral geometry around the copper(II) center. The tert-butyl substituents on the C2-symmetric chiral ligand efficiently shield one of the r-faces of the chelated dienophiles [90, 91]. A variety of substrates readily participate in enantioselective Diels-Alder reactions with copper complex 166. An intramolecular variant of such cycloadditions furnished 167 (96% ee, dr >99 1) and constituted a key step in the synthesis of the marine natural product (-)-isopulo upone... 

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