Intermolecular conjugate additions, enones

In contrast with metal-complex catalyzed transformations [52], enantioselective organocatalyzed intermolecular conjugate additions of O-nudeophiles seem to be limited to peroxides such as hydrogen peroxide or tert-butyl hydroperoxide. In these reactions the primary addition product, a / -peroxy enolate, reacts further to yield an epoxide (Scheme 4.31). Consequently, reactions of this type are covered in Section 10.2 Epoxidation of Enones and Enoates . 

Enones can be activated by triflic anhydride and undergo an intramolecular or intermolecular conjugate addition of an arene ring(105). 3... 

The three examples introduced above involve cyclizations however, numerous methods to effect high levels of stereocontrol in intermolecular conjugate additions of acyclic reactants have been documented. In an extensive series of systematic investigations, Heathcock observed a correlation between enolate geometry, enone structure, and the resulting simple stereo-... 

Michael additions to conjugated carbonyls can be catalyzed by gold species. Among them, arene additions are the most studied area but other nucleophiles can attack the gold-coordinated enones as well. In fact, the intermolecular aza-Michael additions of carbamates to enones was reported in 2002 with both Au(I) and Au(III) salts, and in 2007 an intramolecular aUcoxide and amide conjugate addition has been developed and applied to the synthesis of (+)-andrachcinidine (equation 132). In the latter case, the enones are formed as intermediates in a previous gold-catalyzed step that is the hydration of an alkyne and methanol loss. Then the cyclization takes place to give piperidines. 

Silyl-4-alkenals undergo cyclization which gives 3-cyclopentenols. When the intermolecular allylation of enones which favors the conjugate addition pathway is applied to l,8-bis(trimethylsilyl)-2,6-octadiene the four stereocenters of the 2 1 adduct emerge in a defined fashion. ... 

The tin(IV) enolate can be quenched with a variety of electrophiles to form new carbon-carbon bonds, including carbonyl addition (aldol-type) reactions, alkylations and conjugate additions of tin(IV) enolates. Tin(IV) enolates react readily with aldehydes in both intra- and intermolecular aldol-type reactions [5J]. The best conditions for the intermolecular aldol condensation reaction were to initially generate the tin enolate by reacting the desired enone with tributyltin hydride and then... 

With respect to the substrate scope, ketones are the most efficient nucleophiles although the intermolecular reaction works also well for esters, amides and Weinreb amides (Fig. 2.7). Regarding the Michael acceptor, enones are the best electrophiles with a wide range of substituents tolerated (alkyl, aryl and heteroaryl ketones). a,p-Unsaturated esters, in the case of the intermolecular cyclopropanation, and a,p-unsaturated diimides for the intramolecular reaction, extends the substrate scope of the process (Fig. 2.7). A transition state model for the intramolecular cyclopropanation reaction has been proposed as depicted in Scheme 2.38 for catalyst 65 [106d]. In this model the ammonium salt adopts a conformation that gives the Z-enolate of the nucleophile on deprotonation with the base. The intramolecular conjugate addition of the enolate then takes place through a boat-type transition state. 

These observations led us to examine how conjugated dienones react intermolecularly with trimethylallylsilane. To our initial surprise, treatment of 3-vinyl-2-cyclohexen-l-one (1) with trimethylallylsilane and titanium tetrachloride at -78 C, followed by addition of water to the cold (-78 C) reaction mixture, gave predominantly alcohol 2 silane 2 and enone 4 were minor products (Eq. 4).5e,9 Warming the reaction mixture to room temperature prior to hydrolysis led to only silane 2-... 

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