Asymmetric Carbonyl Olefination

Kiyoshi Tanaka, Takumi Furuta, and Kaoru Fuji 7.1 

It is generally accepted that reactions of carbonyl compounds occupy a central position in organic synthesis and hence in asymmetric synthesis. Thus, the development of new methods for stereoselective or stereocontrolled synthesis involving carbonyl groups has been a major subject in organic chemistry, and in particular much attention has been focused on enantioselective transformations. Efficient and practical asymmetric versions of a variety of ordinary synthetic reactions have 

Various types of phosphorus reagents have been employed for asymmetric transformations of carbonyl compounds into alkenes [2, 4, 7-11]. Depending upon the structure of these reagents, different reaction names are given [3]. Phosphonium ylides and phosphine oxide are particularly popular, and are referred to as Wittig and Horner reagents, respectively. On the other hand, phosphonates and other phosphonic acid derivatives are termed Horner-Wadsworth-Emmons (HWE) reagents. In recent years, arsonium derivatives have often been used for similar reactions, and they are also covered herein. 

Methods for the formation of carbon-carbon double bonds in an asymmetric manner through non-Wittig-type reactions [12,13] have also been reported in recent years, including asymmetric induction by reactions with chiral sulfoxides [13], sul-fones (Julia olefination) [14], sulfoximides [12a, 15], or selenides [16] Pd-catalyzed allylic nucleophilic substitutions [17], as well as asymmetric deprotonation [18]. In the context of the topic of asymmetric carbonyl olefination, some of these asymmetric transformations are beyond the scope of this chapter, although a few of the transformations closely related to the Wittig-type reactions will be discussed in a later part of this chapter. 

As discussed below, the strategies for asymmetric induction through olefination by Wittig-type reactions can be broadly classified into four groups. According to the type of these approaches to optically active olefinic compounds, asymmetric olefi-nations based on Wittig and related reactions will be reviewed in this chapter. 

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Scheme 7.1. The first report of asymmetric carbonyl olefination.

Optically Active Phosphorus or Arsenic Reagents Used in Asymmetric Carbonyl Olefination... 

Scheme 7.5. Three types of chiral phosphorus reagents employed in asymmetric carbonyl olefination.

In a similar manner, asymmetric carbonyl olefination of meso-dicarbonyl compounds was extended to metallic arene or diene complexes [37], such as // -diene Fe or // -arene Cr complexes, to form planar complexes with high enantiomeric bias (Scheme 7.8). Since both complexation and decomplexation of these optically active compounds occur readily, these olefinic complexes are effective as stereocontrollers due to the presence of bulky metal tricarbonyl groups, and serve as useful reactants for obtaining optically active compounds of central chirality by appropriate chemical transformation. 

Scheme 7.8. Asymmetric carbonyl olefinations to give planar chiral alkenes.

Two chiral phosphonic acid derivatives 19a,b, containing a stereogenic phosphorus atom connected to a mercaptoisoborneol moiety, were prepared as a mixture, and were then chromatographically separated. Their ability in asymmetric carbonyl olefination was examined in the reaction with 4-tert-butylcyclohexanone la [56). The two lithium carbanions reacted with the carbonyl group of the substrate to give opposite enantiomers 90a, although no remarkable degree of asymmetric induction was observed (up to 16% ee). 

Scheme 7.19. Asymmetric carbonyl olefinations through kinetic resolution.

Asymmetric carbonyl olefinations through parallel kinetic resolution. 

Scheme 7.26. Some examples of the application of asymmetric carbonyl olefination to natural product synthesis.

Asymmetric Carbonyl Olefinations Without Usage of Optically Active Phosphorus Reagents 329... 

When the achiral phosphonate 182 was reacted with the ketone la in the presence of Sn(II) triflate and N-ethylpiperidine, the chiral diamine 183 was shown to act as a good asymmetric inducer in generating the tetrasubstituted dissymmetric alkene 184 with a high level of enantiomeric excess [35j, 102]. In order to achieve high levels of asymmetric induction, stoichiometric amounts of ligands in relation to the external chiral source were required in all of the aforementioned asymmetric carbonyl olefinations. 

Asymmetric Carbonyl Olefination by Non-Wittig-Type Routes... 

Asymmetric carbonyl olefination methods by routes other than the Wittig and related olefination reactions are available, and some precedents belonging to this... 

By using the same lithium salt (S)-201, asymmetric elimination to give 205 with high diastereotopic differentiation without loss of chirality was reported [15] (Scheme 7.32). This asymmetric carbonyl olefination allowed the selective synthesis of both the (Z)- and ( )-alkenylsulfoximides 208 and 210, which are useful... 

Scheme 7.31. Miscellaneous examples of asymmetric carbonyl olefinations (1).

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