Dissymmetric alkenes

Figure 2 shows the structures of four classes of so-called overcrowded alkenes (see Section 5.3.1), designed as molecular components for a chiroptical switch based on CPL irradiation.1191 Thanks to unfavorable steric interactions around the central ole-finic bond, the molecules are forced to adopt a helical shape. The chirality in these inherently dissymmetric alkenes - denoted M and P for left-handed and right-handed helices, respectively - therefore originates from distortion of the molecular... 

Tab. 1 Anisotropy factors of different types of inherently dissymmetric alkenes.

The sterically overcrowded alkenes shown in Scheme 6 have been exploited in our group since, from the perspective of molecular switches design, they combine a number of attractive structural features. Steric interactions between the groups attached to the central olefmic bond force these molecules to adapt a non-planar helical shape. The chirality of these so-called inherently dissymmetric alkenes 3, is therefore the result of distortion of the entire molecular structure. Beside the heli-cene-like geometry, both a cis- and a trans-stilbene chromophore are present in the same molecule. 

Secondary thioamides, precursors of N-protonated azomethine ylids, give A1-pyrrol ine derivatives (after elimination of thiol). When the dipolarophiles are dissymmetric alkenes, high regioselectivity is obtained. Reaction with alkynes leads to pyrrole derivatives in good to excellent yields and with ArCHO leads regioselectively to 2,5-disubstituted 2-oxazolidines in moderate yields.264... 

Three types of cycloaddition products are generally obtained from the photochemical reaction between aromatic compounds and alkenes (Scheme 31). While [2 + 2] (ortho) and [3 + 2] (meta) cycloaddition are frequently described, the [4 + 2] (para or photo-Diels-Alder reaction) pathway is rarely observed [81-83]. Starting from rather simple compounds, polycyclic products of high functionality are obtained in one step. With dissymmetric alkenes, several asymmetric carbons are created during the cycloaddition process. Since many of the resulting products are interesting intermediates for organic syntheses, it is particularly attractive to perform these reactions in a diastereoselective way. 

The reaction of chiral phosphonium ylide or related reagent with a 4-substituted cyclohexanone gives an axially dissymmetrical alkene. For example, alkenation of 4-methylcyclohexanone (4.40) with chiral ylide 4.41 containing stereogenic centre on phosphorus gives optically active alkene (S)-(+)-4.42 in 43% yield . 

Figure 87 A chiroptical molecular switching process based on donor-acceptor-substituted dissymmetric alkenes. ...

Scheme 7.13. Asymmetric carbonyl olefinations to give dissymmetric alkenes (2).

The HWE reactions of 4-tert-butylcydohexanone (la) with reagent 176 in the presence of the alkoxide of chiral amino alcohol 178 as a base resulted in the formation of dissymmetric alkene 179 in good yield with up to 52% ee [100] (Scheme 7.29). In this study, it was suggested that the addition step is reversible and that the... 

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. 

The use of a substoichiometric amount (20 mol%) of an external chiral source was first demonstrated in the asymmetric olefination of a 4-substituted cyclohexanone [103] by using a chiral phase-transfer catalyst 186 derived from cinchonine here, a combination of the chiral phase-transfer catalyst and rubidium hydroxide as a base was essential in generating the dissymmetric alkene 187 with 57% ee after a re-esterification step (Scheme 7.30). Though the problem of low turnover still has to be solved, this result provided an informative concept for the... 

Besides the use of chiral bases or catalysts in solution, a rather interesting and unique approach that belongs to the present category involves the utilization of inclusion complexes of the stabilized ylides [104]. In the solid state, an achiral stabilized ylide such as 190 is reacted with a symmetrically substituted prochiral cyclohexanone such as 189 in the presence of a chiral host molecule. The best result was obtained using the chiral host molecule 191, which gave the dissymmetric alkene 192 with up to 57% ee. 

Fig. 2 Inherently dissymmetric over-TyP 3 Type 4 crowded alkenes.

Protons are even smaller than F+, so they should give open transition states and nonstereoselective additions, which have been confirmed experimentally.126 A loss of stereoselectivity can even be observed during the bromination of certain substituted alkenes. The HOMO, and hence the bromonium ion, are dissymmetric and an equilibrium can be established with the open form. In some cases, such as the benzylic cation below, this form dominates. 

With dissymmetrical alkynes or alkenes, very clean reactions are often obtained by regiospecific processes see Regioselectivity) For example, the use of phosphorus unsaturated reagents afford the opportunity to generate various mono or diphosphanes and related species (Scheme 29). ... 

Asymmetric Alkene Isomerization. The chiral titanocene reagent (1) serves as precatalyst for the isomerization of alkene (4) (eq 3). Active isomerization catalyst is obtained by in situ reduction of (1) with Lithium Aluminum Hydride (164 °C, 30 min). Treatment of the achiral substrate (4) with 2 mol % catalyst produced axially dissymmetric product (5)-(5) in 44-76% ee (100% yield). The reaction is slow at room temperature (120 h required for complete reaction) faster rates are obtained at higher temperatures, but at the expense of lower product enantiomeric purity. 

The first well-defined, stable d°-alkylidene species having catalytic activity in alkene metathesis was Ta(=CHtBu)(OtBu)2Cl(PMe3) (5) [16]. However, research efforts moved rapidly to Mo and/or W alkylidenes, first in the form of 0X0 complexes (6) [17, 26], and then with the more easily accessible, imido bisalkoxy alkylidene complexes of general formula M(=NR )(=CHR )(OR )2 (7) [18, 19, 27], as well as the isoelectronic Re-alkylidyne-alkylidene complexes Re(=CR )(=CHR )(OR )2 (8) [28]. In 2001, it was shown that the silica-supported, Re-alkylidyne-alkylidene complex (=SiO)Re(=CtBu)(=CHtBu)(CH2tBu) (12) was unexpectedly very active [21,29]. According to computational studies, which will be described later in this chapter, the remarkable reactivity of this silica-supported catalyst arises from the different nature of the X and Y ligands (referred to as dissymmetric complexes) [7]. In addition, new molecular precursors based on bis-alkyl and bis-pyrrolyl M(=NR )(=CHR )(X)2 complexes became available [30]. Consequently, from 2005, considerable research effort has been devoted toward generating silica-supported (14 to 16 in Scheme 6.4) [23, 31, 32] and molecular (17 and 18 in Scheme 6.4) [22, 33, 34] Mo- and W-imido complexes... 

Shibata and coworkers have developed a Rh-catalyzed, highly enantioselective [2 + 2-1-2] cycloaddition of 1,6-diynes 33 and alkenes using an optimized rhodium catalyst (Scheme 9.9) [18], Without any additive other than the catalyst, the use of cjt -methylene cyclic ketones 34 or lactones 35 as activated alkenes allowed access to chiral spirocyclic structures 36. Interestingly, an impressive regioselectivity along with good enantioselectivity were observed when a dissymmetric 1,6-diyne was used in the process. 

The chiral phosphonates 31a,e, possessing optically active BINOL as an auxiliary, also demonstrated their ability as asymmetric inducers in the dissymmetrization of carbonyl compounds. In order to achieve both high enantioselectivity and good chemical yield, addition of zinc chloride was quite effective in these transformations [8]. It is known that bicydo[3.3.0]octane derivatives usually adopt either W-, S-, or V-shaped conformations, and the observed stereochemistry of the alkene 92a was best explained by considering an initial approach of the nucleophile to the W-shaped bicyclo[3.3.0]octanone in the direction in which steric interaction between the reagent and the substrate is minimized. 

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