Intermolecular Carbonyl-Alkene Couplings

The ketyl radical anion intermediates can be exploited in carbon-carbon bond-forming reactions. Intermolecular and intramolecular pinacol couplings between the carbonyl groups of ketones and aldehydes are well known (Chapter 5, Section 5.1), as are intermolecular and intramolecular carbonyl-alkene couplings (Chapter 5, Section 5.2). 

The intermolecular McMurry reaction is first of all a suitable method for the synthesis of symmetrical alkenes. With a mixture of carbonyl compounds as starting material, the yield is often poor. An exception to this being the coupling of diaryl ketones with other carbonyl compounds, where the mixed coupling product can be obtained in good yield. For example benzophenone and acetone (stoichiometric ratio 1 4) are coupled in 94% yield. ... 

Intermolecular coupling of ketones and alkenes, promoted by SmH, occurs with excellent stereochemical control. In one such reaction, samarium(II) iodide has been used to prepare cyclobutanones and cyclobutanols from chiral, 6-oxohex-2-enoates (equation 137)520. The reaction is performed in THF in the presence of HMPT and occurs in good yield with excellent stereocontrol. If appropriately located carbonyl and alkene moieties are present in a molecule, then Sml2-HMPT can be used to form cyclooctanols by a radical cyclization process in some cases there is a reasonable degree of diastereoselectivity (equation 138)521,522. 

Another useful reaction for the difunctionalization of olefins involves a group transfer carbonylation starting from a a-(phenylseleno)carbonyl (or related derivatives) and a terminal alkene under 80 atm of CO. An alkyl radical is first formed by the photocleavage of a C-SePh bond. The addition of this radical to the olefin, followed by the incorporation of CO and radical coupling with PhSe-, gave substituted selenoesters via a three-component coupling reaction [74], The intermolecular formation of C—C bonds via phenylseleno group transfer has been likewise adopted in the reaction between ester-substituted O,Se-acetals and an olefin [75],... 

Silicon substituents are known to stabilize both radical and carbanion centers. Thus, better and more consistent yields are obtained from intermolecular coupling reactions using trimethylsilyl substituted alkenes such as VII as substrates for reaction with carbonyl... 

The intermolecular McMurry carbonyl coupling reaction has been applied to the synthesis of a variety of symmetrically and, in certain cases, unsymmetrically substituted alkenes. 

Unsymmetrical alkenes can be prepared by mixed intermolecular reactions if one of the components, commonly acetone, is used in excess (equation 83). As the isopropyl group is a common subunit of many terpenes this method provides a valuable route for its introduction. Pattenden and Robertson used such a reaction followed by a Grob-type fragmentation in their preparation of the daucenone (42) from the readily enolized ketone (43). The bicycle (42) was used as an intermediate for the synthesis of the diterpene ( )-isoamijiol (44 equation 84). Mixed couplings are not restricted to acetone, and almost any carbonyl may be used. For example, Paquette et al. employed the aldehyde (45) in a synthesis of ( )-a-vetispirene (46 equation 85). More complex mixed couplings are also possible. For example, the aldehydes (47) and (48) are coupled efficiently to the stilbene (49), which in turn is converted to phenan-threne alkaloids such as atherosperminine and thalictuberine (equation 86). ... 

In a similar manner, cyclopropane-containing benzvalene can be used as the alkene component in intermolecular Pauson-Khand reactions.Several examples of intermolecular Pauson-Khand cyclizations of methylenecyclopropanes and alkynes are reported to give bicyclic car-bocycles. Ethynylcyclopropyl-substituted chromium carbonyl complexes have also been used in palladium-catalyzed coupling reactions. 

An experimental and computational study describing a cascade transformation that breaks all three C-C bonds in a polarized alkyne moiety has been reported (Scheme 5)." Facile intermolecular Michael addition is followed by the relatively slow intramolecular steps. The slowest step corresponds to the 5-exo trig closure at the carbonyl-substituted alkene. This process is facilitated by the coupling of the intramolecular Michael addition with a concerted proton transfer along a resonance-assisted hydrogen bond path, which avoids the formation of an unfavourable zwitterionic intermediate. 

In addition to the iminium-salt-based chemistry and to cross-coupling processes, aqueous formaldehyde can also be used as the carbonylated substrate in the Prins reaction, an intermolecular ene-type acid-catalyzed reaction with alkenes providing 1,3-dioxanes (Adams and Bhatnagar, 1977). 

Alkenes may be generated via the intra- or intermolecular reductive coupling of carbonyl compounds in a titanium-mediated process known as the McMurry coupling. ... 

---