Metallo-ene process

In contrast, intramolecular versions of the metallo-ene process may be regio- and stereo-selective as well as entropically favored and are thus more efficient, similar to intramolecular ene reactions (Volume 5, Chapter 1.1) and [4 + 2] cycloadditions (Volume 5, Chapter 4.4). This holds for two different modes of cyclization in which the enophile is linked by a suitable bridge, either to the terminal carbon atom C-3 (type I) or to the central carbon aton C-2 (type II) of the metallo-ene unit (Scheme 18). The prc nsity of the cyclized alkylmetal intermediates (F) and (H) for further functionalizations and cycli-zations, involving the metallated and two alkenic sites, offers a considerable potential in organic synthesis. 

A tin-mediated ene reaction on the chiral glyoxylate ester (265, R = chiral group) has yielded the verrucarinic acid precursor (266) as virtually a single enantiomer (168). The selectivity of this metallo-ene process stands in sharp contrast to the proto-ene reaction (129) which produces a mixture of diastereomers (267) and (268) in low yield. 

The perfect diastereoselectivity observed in these reactions lead to the assumption that they do not proceed via a simple anionic intramolecular cyclization (i.e. carbozincation) as was proposed in earlier61 publications. Cyclizations of non-propargylic substrates15,62 were shown to proceed with significantly lower diastereoselectivity (cis/trans typically 75/25). Thus, in the case of propargylic compounds, e.g. 114, a simple carbozincation process is unlikely to be operative. It was therefore reasoned that the active species in these reactions is not 115-ZnBr but rather its allenic isomer 120, which undergoes a metallo-ene-allene reaction in a chair-like transition state as depicted in equation 5659a. 

A seven-membered ring oxygen heterocycle 176 could also be generated by type intramolecular metallo-ene reactions and the zinc-ene process appeared by far more efficient than the magnesium-ene. However, in the nitrogen series, type II zinc-and magne-sium-ene reactions exhibited similar efficiencies and afforded the substituted 3-methylene piperidine 177 in comparable yields (equation 86)121. 

Two other Ni(CO)4 substitutes, Ni(CO)3PPh3 and Ni(COD)2/dppe, prove to be appropriate for the catalysis of tandem metallo-ene/carbonylation reactions of allylic iodides (Scheme 7)399. This process features initial oxidative addition to the alkyl iodide, followed by a metallo-ene reaction with an appropriately substituted double or triple bond, affording an alkyl or vinyl nickel species. This organonickel species may then either alkoxycar-bonylate or carbonylate and undergo a second cyclization on the pendant alkene to give 51, which then alkoxycarbonylates. The choice of nickel catalyst and use of diene versus enyne influences whether mono- or biscyclization predominates (equations 200 and 201). 

Starting with a few reports in the early 1960s, additions of allylmetal compounds to alkenes and al-kynes became increasingly acknowledged. These reactions resemble the classical ene process (Scheme 1), but involve a transfer of a metal instead of a hydrogen. This analogy prompted Of lzer to classify transformations like (A) -h (B) (D), with X = metal, as metallo-ene reactions. However, allylmetal... 

Tetracarbonylnickel is an inexpensive (although toxic) source of Ni° and its use for the in situ generation of allylnickel intermediates dates back at least 25 years. In fact, the nickel allylation/methoxycarbo-nylation of alkynes with allyl chloride and an excess of Ni(CO)4 in methanol has b n reviewed (Scheme 15). Accordbgly, dienoates (68) (35-80%) were obtained in a regio- and stereo-selective manner corresponding to a metallo-ene cis addition of an allylnickel compound at the less-substituted termirud C-1 of (67), followed by a CO insertion into the resulting vinylnickel species. The dienyl esters (68) were accompanied by variable amounts of cyclopentenones, indicating the possibility of consecutive CO insertion processes. 

The cyclization of allylic acetates tethered with alkenes has been extensively investigated by Oppolzer, employing a number of transition metals including nickel. The process has been termed a metallo-ene reaction however, the mechanism likely involves a sequence of oxidative addition to generate a jt-aUyl complex, alkene insertion, and P-hy-dride elimination. The process is quite general in scope and provides a very useful method for the preparation of 1,4-dienes such as 46 (Scheme 28). 

The mechanism of addition of allylzinc reagents to vinylmetallics (including vinyllithium) has been probed using DFT calculations with both the metallo-ene and metallo-Claisen processes being studied. Finally, an ab initio analysis of the structures of lithium and sodium pentadienyl points to the stability of a U-shaped structure which maximises metal centre coordination. ... 

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