Chiral Dipolars

At the same time the dopant induces the spontaneous polarization (Ps) in the mixture [50, 51]. The magnitude of the spontaneous polarization increases with the increasing concentration of a chiral dipolar dopant, Fig. 1.19 [51]. With doping, rather high values of Pg, of the order of 10-100 nC cm , can be obtained. 

FIGURE 1.19. Temperature dependence of the spontaneous polarization induced by the chiral dipolar dopant L-4-decloxybenzylidene-4 - aunino-2-cyano-propylcinnamate in the achiral smectic C matrix of 4-nonyloxy-benzy-hdene-4 -amino-pentylcinnamate. The concentration of the dopant is indicated in weight percent. 

A special strategy has been developed for composing ferroelectric mixtures. Such materials are based on chiral dipolar compounds which form the smectic C phase. The chemical synthesis of such compounds is extremely difficult. However, the problem can be solved step by step an achiral smectic C matrix with a wide temperature range may be worked out separately, and then doped by a chiral dipolar additive (the chirality and dipole moment cannot be decoupled from each other, as was discussed in Section 1.2.5). 

As witli tlie nematic phase, a chiral version of tlie smectic C phase has been observed and is denoted SniC. In tliis phase, tlie director rotates around tlie cone generated by tlie tilt angle [9,32]. This phase is helielectric, i.e. tlie spontaneous polarization induced by dipolar ordering (transverse to tlie molecular long axis) rotates around a helix. However, if tlie helix is unwound by external forces such as surface interactions, or electric fields or by compensating tlie pitch in a mixture, so tliat it becomes infinite, tlie phase becomes ferroelectric. This is tlie basis of ferroelectric liquid crystal displays (section C2.2.4.4). If tliere is an alternation in polarization direction between layers tlie phase can be ferrielectric or antiferroelectric. A smectic A phase foniied by chiral molecules is sometimes denoted SiiiA, altliough, due to the untilted symmetry of tlie phase, it is not itself chiral. This notation is strictly incorrect because tlie asterisk should be used to indicate the chirality of tlie phase and not tliat of tlie constituent molecules. 

Other approaches to (36) make use of (37, R = CH ) and reaction with a tributylstannyl allene (60) or 3-siloxypentadiene (61). A chemicoen2ymatic synthesis for both thienamycia (2) and 1 -methyl analogues starts from the chiral monoester (38), derived by enzymatic hydrolysis of the dimethyl ester, and proceeding by way of the P-lactam (39, R = H or CH ) (62,63). (3)-Methyl-3-hydroxy-2-methylpropanoate [80657-57-4] (40), C H qO, has also been used as starting material for (36) (64), whereas 1,3-dipolar cycloaddition of a chiral nitrone with a crotonate ester affords the oxa2ohdine (41) which again can be converted to a suitable P-lactam precursor (65). 

Separation of enantiomers by physical or chemical methods requires the use of a chiral material, reagent, or catalyst. Both natural materials, such as polysaccharides and proteins, and solids that have been synthetically modified to incorporate chiral structures have been developed for use in separation of enantiomers by HPLC. The use of a chiral stationary phase makes the interactions between the two enantiomers with the adsorbent nonidentical and thus establishes a different rate of elution through the column. The interactions typically include hydrogen bonding, dipolar interactions, and n-n interactions. These attractive interactions may be disturbed by steric repulsions, and frequently the basis of enantioselectivity is a better steric fit for one of the two enantiomers. ... 

The origin of stereoselection in 1,3-dipolar cycloadditions to chiral alkenes 97G167. 

The use of chiral dipolarophiles, such as the nitrile oxide additions to chiral furanones, have received much interest. The cycloaddition of various 1,3-dipolar reagents to the enantiomeric ally pure furanones 170 and 227 showed excellent diastereofacial control by the menthyloxy substituent, especially in nitrone and nitrile oxide additions (cf. Table II) (88TL5317). 

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. 

Finally, there is the enantioselectivity of the 1,3-dipolar cycloaddition reactions. This chapter is limited to describing only the metal-catalyzed asymmetric 1,3-dipolar cycloaddition reactions that involve non-chiral starting materials. The only fac-... 

The above described reaction has been extended to the application of the AlMe-BINOL catalyst to reactions of acyclic nitrones. A series chiral AlMe-3,3 -diaryl-BINOL complexes llb-f was investigated as catalysts for the 1,3-dipolar cycloaddition reaction between the cyclic nitrone 14a and ethyl vinyl ether 8a [34], Surprisingly, these catalysts were not sufficiently selective for the reactions of cyclic nitrones with ethyl vinyl ether. Use of the tetramethoxy-substituted derivative llg as the catalyst for the reaction significantly improved the results (Scheme 6.14). In the presence of 10 mol% llg the reaction proceeded in a mixture of CH2CI2 and petroleum ether to give the product 15a in 79% isolated yield. The diastereoselectiv-ity was the same as in the acyclic case giving an excellent ratio of exo-15a and endo-15a of >95 <5, and exo-15a was obtained with up to 82% ee. 

The high enantioselectivity of the exo product opens up a new and readily accessible route to an enantioselective synthesis of interesting isoquinoline alkaloids (Scheme 6.15) [35]. The tricyclic isoxazolidine exo-15b was obtained from the 1,3-dipolar cydoaddition reaction as the pure exo isomer and with 58% ee [34]. As shown in Scheme 6.15 the exo product from the 1,3-dipolar cydoaddition was converted into 17 in two steps without racemization at the chiral center. In addition to the illustrated synthesis, the 6,7-dimethoxy-derived isoxazolidine exo-15b is a very useful precursor for the synthesis of naturally occurring isoquinoline alkaloids [36-40]. 

Several titanium(IV) complexes are efficient and reliable Lewis acid catalysts and they have been applied to numerous reactions, especially in combination with the so-called TADDOL (a, a,a, a -tetraaryl-l,3-dioxolane-4,5-dimethanol) (22) ligands [53-55]. In the first study on normal electron-demand 1,3-dipolar cycloaddition reactions between nitrones and alkenes, which appeared in 1994, the catalytic reaction of a series of chiral TiCl2-TADDOLates on the reaction of nitrones 1 with al-kenoyloxazolidinones 19 was developed (Scheme 6.18) [56]. These substrates have turned out be the model system of choice for most studies on metal-catalyzed normal electron-demand 1,3-dipolar cycloaddition reactions of nitrones as it will appear from this chapter. When 10 mol% of the catalyst 23a was applied in the reaction depicted in Scheme 6.18 the reaction proceeded to give a yield of up to 94% ee after 20 h. The reaction led primarily to exo-21 and in the best case an endo/ exo ratio of 10 90 was obtained. The chiral information of the catalyst was transferred with a fair efficiency to the substrates as up to 60% ee of one of the isomers of exo3 was obtained [56]. 

A quite different type of titanium catalyst has been used in an inverse electron-demand 1,3-dipolar cycloaddition. Bosnich et al. applied the chiral titanocene-(OTf)2 complex 32 for the 1,3-dipolar cycloaddition between the cyclic nitrone 14a and the ketene acetal 2c (Scheme 6.25). The reaction only proceeded in the presence of the catalyst and a good cis/trans ratio of 8 92 was obtained using catalyst 32, however, only 14% ee was observed for the major isomer [70]. 

A mechanism for this reaction has been proposed [75], The first key intermediate in the reaction is the copper(I) acetylide 42. The additional ligand may be solvent or H2O. The acetylene moiety in 42 is activated for a 1,3-dipolar cycloaddition with the nitrone to give intermediate 43, with introduction of chirality in the product. A possible route to ris/traws-41 might be via intermediate 44. Finally, the cis isomer is isomerized into the thermally more stable trans-41. It should be mentioned that the mechanism outlined in Scheme 6.32 was originally proposed for a racemic version of the reaction to which water was added. 

In 1997 the application of two different chiral ytterbium catalysts, 55 and 56 for the 1,3-dipolar cycloaddition reaction was reported almost simultaneously by two independent research groups [82, 83], In both works it was observed that the achiral Yb(OTf)3 and Sc(OTf)3 salts catalyze the 1,3-dipolar cycloaddition between nitrones 1 and alkenoyloxazolidinones 19 with endo selectivity. In the first study 20 mol% of the Yb(OTf)2-pyridine-bisoxazoline complex 55 was applied as the catalyst for reactions of a number of derivatives of 1 and 19. The reactions led to endo-selective 1,3-dipolar cycloadditions giving products with enantioselectivities of up to 73% ee (Scheme 6.38) [82]. In the other report Kobayashi et al. described a... 

Grigg et al. have found that chiral cobalt and manganese complexes are capable of inducing enantioselectivity in 1,3-dipolar cycloaddition reactions of azomethine... 

In a more recent publication the same group mentions that Ag(I) salts in combination with chiral phosphine ligands can catalyze the 1,3-dipolar cycloaddition involving the azomethine precursor 64b and methyl vinyl ketone (Scheme 6.43) [87]. The reaction, which presumably also required a stoichiometric amount of the catalyst, proceeds to give 65b in a good yield with 70% ee. 

Although the first metal-catalyzed asymmetric 1,3-dipolar cycloaddition reaction involved azomethine ylides, there has not been any significant activity in this area since then. The reactions that were described implied one of more equivalents of the chiral catalyst, and further development into a catalytic version has not been reported. 

The rhodium-catalyzed tandem carbonyl ylide formation/l,3-dipolar cycloaddition is an exciting new area that has evolved during the past 3 years and high se-lectivities of >90% ee was obtained for both intra- and intermolecular reactions with low loadings of the chiral catalyst. 

Dipolar cydoadditions are one of the most useful synthetic methods to make stereochemically defined five-membered heterocydes. Although a variety of dia-stereoselective 1,3-dipolar cydoadditions have been well developed, enantioselec-tive versions are still limited [29]. Nitrones are important 1,3-dipoles that have been the target of catalyzed enantioselective reactions [66]. Three different approaches to catalyzed enantioselective reactions have been taken (1) activation of electron-defident alkenes by a chiral Lewis acid [23-26, 32-34, 67], (2) activation of nitrones in the reaction with ketene acetals [30, 31], and (3) coordination of both nitrones and allylic alcohols on a chiral catalyst [20]. Among these approaches, the dipole/HOMO-controlled reactions of electron-deficient alkenes are especially promising because a variety of combinations between chiral Lewis acids and electron-deficient alkenes have been well investigated in the study of catalyzed enantioselective Diels-Alder reactions. Enantioselectivities in catalyzed nitrone cydoadditions sometimes exceed 90% ee, but the efficiency of catalytic loading remains insufficient. 

To control the stereochemistry of 1,3-dipolar cycloaddidon reacdons, chiral auxiliaries are introduced into either the dipole-part or dipolarophile A recent monograph covers this topic extensively ° therefore, only typical examples are presented here. Alkenes employed in asymmetric 1,3-cycloaddidon can be divided into three main groups (1) chiral allyhc alcohols, f2 chiral amines, and Hi chiral vinyl sulfoxides or vinylphosphine oxides. 

Enandoselecdve total synthesis of andhingal agent Sch-38516 is reported. Stereocontrolled carbohydrate synthesis is based on the 1,3-dipolar cycloaddidon of chiral nkrone to vinylene carbonate, as shovm in Eq. 8.53. ... 

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