Conjugate additions catalyzed by Lewis acids

FIGURE 23.11 Conjugate additions catalyzed by Lewis acids. 

Fluorinated carbocations play an important role as intermediates in electrophilic reactions of fluoroolefins and other unsaturated compounds. For example, F-allyl cation 1 was proposed as a reactive intermediate in reactions of HFP with fluoroolefins catalyzed by Lewis acids [7]. The difference in stability of the corresponding allylic cations was suggested as the explanation for regio-specific electrophilic conjugated addition to CF2=CC1CF=CF2 [11]. Allylic polyfluorinated carbocations were proposed as intermediates in the reactions of terminal allenes with HF [53] and BF3 [54], ring-opening reactions of cyclopropanes [55], Carbocations are also an important part of the classic mechanism of electrophilic addition to olefins (see Eq. 2). This section deals with the questions of existence and stability of poly- and perfluorinated carbocations. 

Conjugate additions of enolates or their equivalents to enones are also catalyzed by Lewis acids, and again enantioselective versions of the reactions have proved to be very useful (Figure 23.11). 

Finally in 2005, Hutt and Mander reported their strategy for the synthesis of nominine (Scheme 1.3) [29], The approach relies upon construction of the steroidal ABC carbocyclic ring structure followed by stepwise preparation of the fused aza-ring system. In the key sequence of the synthetic study, enone 50 was oxidized to dienone 51 with DDQ followed by Lewis acid-catalyzed intramolecular conjugate addition of the methylcarbamate to the newly formed dienone to deliver pyrrolidine 52. 

The combination of X2/protic acid (X2=Cl2,Br2> I2) is usually ineffective for reactions of conjugate addition, due to formation of significant amounts of a halogenation product. However, addition of a Lewis acid may alter the course of the reaction. For example, fluorosulfate 44 was isolated in 84% yield in the reaction of HFP with C12/H0S02F catalyzed by SbF5, but in the absence of the catalyst no formation of 44 was observed [82] ... 

Gothelf presents in Chapter 6 a comprehensive review of metal-catalyzed 1,3-di-polar cycloaddition reactions, with the focus on the properties of different chiral Lewis-acid complexes. The general properties of a chiral aqua complex are presented in the next chapter by Kanamasa, who focuses on 1,3-dipolar cycloaddition reactions of nitrones, nitronates, and diazo compounds. The use of this complex as a highly efficient catalyst for carbo-Diels-Alder reactions and conjugate additions is also described. 

The l ,J -DBFOX/Ph-transition metal aqua complex catalysts should be suitable for the further applications to conjugate addition reactions of carbon nucleophiles [90-92]. What we challenged is the double activation method as a new methodology of catalyzed asymmetric reactions. Therein donor and acceptor molecules are both activated by achiral Lewis amines and chiral Lewis acids, respectively the chiral Lewis acid catalysts used in this reaction are J ,J -DBFOX/Ph-transition metal aqua complexes. 

Since aromatic substitutions, aliphatic substitutions, additions and conjugate additions to carbonyl compounds, cycloadditions, and ring expansion reactions catalyzed by Fe salts have recently been summarized [17], this section will focus on reactions in which iron salts produce a critical activation on unsaturated functional groups provided by the Lewis-acid character of these salts. 

Ferrocen-l,l -diylbismetallacycles are conceptually attractive for the development of bimetal-catalyzed processes for one particular reason the distance between the reactive centers in a coordinated electrophile and a coordinated nucleophile is self-adjustable for specific tasks, because the activation energy for Cp ligand rotation is very low. In 2008, Peters and Jautze reported the application of the bis-palladacycle complex 56a to the enantioselective conjugate addition of a-cyanoacetates to enones (Fig. 31) [74—76] based on the idea that a soft bimetallic complex capable of simultaneously activating both Michael donor and acceptor would not only lead to superior catalytic activity, but also to an enhanced level of stereocontrol due to a highly organized transition state [77]. An a-cyanoacetate should be activated by enolization promoted by coordination of the nitrile moiety to one Pd(II)-center, while the enone should be activated as an electrophile by coordination of the olefinic double bond to the carbophilic Lewis acid [78],... 

Addition of azide ion to conjugated systems can be carried out by using NaN3 and acetic acid in water (Eq. 10.18).38 Some reactions were very rapid while others took 1 to 3 days to complete. Lewis base was found to catalyze such conjugate additions of azide ion to cyclic enones in water.39... 

This chapter will begin with a discussion of the role of chiral copper(I) and (II) complexes in group-transfer processes with an emphasis on alkene cyclo-propanation and aziridination. This discussion will be followed by a survey of enantioselective variants of the Kharasch-Sosnovsky reaction, an allylic oxidation process. Section II will review the extensive efforts that have been directed toward the development of enantioselective, Cu(I) catalyzed conjugate addition reactions and related processes. The discussion will finish with a survey of the recent advances that have been achieved by the use of cationic, chiral Cu(II) complexes as chiral Lewis acids for the catalysis of cycloaddition, aldol, Michael, and ene reactions. 

The electrophilic addition of hydrogen sulfide and 1-butanethiol to 1,3-conjugated dienes49 in chloroform at —10 °C has been reported in a quite old paper of a Russian team. The yields were generally low, in the range of 20%, even when the reaction was catalyzed by a mixture of two Lewis acids, EtAlB /EtAlC however, polymerization of the diene was not significant. 

The Lewis acid catalyzed conjugate addition of allylsilanes (140) to (142) and allylstannanes (154) and (155) to ot,0-enones, described by Sakurai,68a,68b is highly efficient and experimentally simple in contrast to the allylcuprate additions. Various substituents can be incorporated into the allylsilanes (allylstannanes), e.g. alkoxy, alkoxycarbonyl and halogen, some of which are incompatible with cuprate reagents 69 In addition, Heathcock and Yamamoto report that diastereoselectivity is correlated to the alkene geometry of both the allylmetals and the acceptor units for example, allylation of ( )-enones (143) and (146) affords predominantly the syn adducts (144) and (147), while (Z)-enone (149) gives predominantly the anti adduct (150 Scheme 25).680 On the other hand, with cyclohexen-2-one the (Z)-silane (141) affords predominantly the threo adduct (152), while (142) affords erythro adduct (ISS).686 The more reactive allylstannanes (154) and (155) also afford similar diastereoselectivity.68e,f... 

---