Induction 1,3-asymmetric

The conception of asymmetric synthesis has hitherto been based on Marckwald s classical definition (99)  

Asymmetric induction is a conception of fundamental significance, which keeps recurring throughout the literature of stereochemistry, yet 

An effect of this type is obviously intermolccular, but it will be shown below that phenomena are also known which exemplify what may be considered as intramolecular asymmetric inductions. 

McKenzie and co-workers (87,89,90,123) tentatively applied the conception to the mechanism of asymmetric syntheses of the following type, where R is an optically active radical such as ( —)-menthyl, and C 

It was suggested that such a reaction involved the following stages  

The formation of a chiral substance from an achiral starting material is called asymmetric induction. Glycerol has a symmetric molecule, but when it is held on the surface of an enzyme and one hydroxyl group is 

Cornforth, Stereochemistry of life. Interdisciplinary Science Reviews, 1984, 9, 393-398. 

Haslam, Metabolites and Metabolism, Oxford University Press, Oxford, 1985, pp. 161. 

Insect Biochemistry, Chapman and Hall, London, 1977, pp. 64. 

A special case of asymmetric enantiomer-differentiating polymerization is the isoselective copolymerization of optically active 3-methyl-1-pentene with racemic 3,7-dimethyl-1-octene by TiCl4 and diisobutylzinc [CiardeUi et al., 1969]. The copolymer is optically active with respect to both comonomer units as the incorporated optically active 3-methyl-1-pentene directs the preferential entry of only one enantiomer of the racemic monomer. The directing effect of a chiral center in one monomer unit on the second monomer, referred to as asymmetric induction, is also observed in radical and ionic copolymerizations. The radical copolymerization of optically active a-methylbenzyl methacrylate with maleic anhydride yields a copolymer that is optically active even after hydrolytic cleavage of the optically active a-methylbenzyl group from the pol3mier [Kurokawa and Minoura, 1979]. Similar results were obtained in the copolymerizations of mono- and di-/-menthyl fumarate and (—)-3-(P-styryloxy)menthane with styrene [Kurokawa et al., 1982]. 

The stereochemistry of ring-opening polymerizations has been studied for epoxides, episul-fides, lactones, cycloalkenes (Sec. 8-6a), and other cyclic monomers [Pasquon et al., 1989 Tsuruta and Kawakami, 1989]. Epoxides have been studied more than any other type of monomer. A chiral cyclic monomer such as propylene oxide is capable of yielding stereoregular polymers. Polymerization of either of the two pure enantiomers yields the isotactic polymer when the reaction proceeds in a legioselective maimer with bond cleavage at bond 1. 

Polymerization of racemic propylene oxide proceeds differently depending on the initiator. Polymerization by potassium hydroxide or alkoxide proceeds with better than 95% regioselectivity of cleavage at bond 1, but the product is atactic [Tsuruta and Kawakami, 1989]. Both (R)- and (S)-propylene oxide react at the same rate as shown by the invariance 

The stereochemistry of ring-opening polymerizations of episulfides, lactones, lactides, V-carboxy-a-amino acid anhydrides, and other monomers has been studied but not as extensively as the epoxides [Boucard et al., 2001 Chatani et al., 1979 Duda and Penczek, 2001 Elias et al, 1975 Guerin et al., 1980 HaU and Padias, 2003 Imanishi and Hashimoto, 1979 Inoue, 1976 Ovitt and Coates, 2000 Spassky et al., 1978 Zhang et al., 1990]. 

Theoretical questions played a minor role in his thoughts.. . . Emil Fischer was the clever tactician who proceeded on a broad front.. . . There were many who were better read than he, but no-one who had more practical experience. 

Whereas the configurations of the sugars are truly a lasting monument to Emil Fischer, the concept of asymmetric induction, also referred to as partial asymmetric synthesis, initiated a new era in chemical research that is still with us today. 

The modem concept of asymmetric induction is illustrated by the formulas in Fig. 1. As shown, the addition of hydrogen cyanide to the optically active aldehyde can lead to two diastereomers (1 and 2). If the process is under thermodynamic control, the formation of the more stable isomer will be favored that is, that isomer for which the non-bonded interactions between the newly formed cyano and the hydroxyl groups with the dissymmetric R group are weakest. On the other hand, the difference in the yields of 1 and 2 can be the result of kinetic control arising from a difference in the energies of the transition states—that state with the lower energy will form faster and lead to the product of higher yield. It is noteworthy that the tenets 

All previous observations in the sugar group are in such complete agreement with the van t 

Hoff- Le Bel theory ofthe asymmetric carbon that the use ofthis theory seems justifiable. 

The crystal of VII has two crystallographically independent molecules, A and B, in the PI cell. Both of the 2-ce groups of A and B take the perpendicular conformation and are contacts with each other around a pseudo inversion center. The crystal was irradiated with a xenon lamp for a week until the crystal was decomposed. The crystal analyzed by X-rays showed no change. This is because the conformation of the 2-ce group is perpendicular to the cobaloxime plane and the cavity volumes, 12.1 and 14.0 for A and B, are too small. The crystal of VIII suitable for X-ray work was not obtained. 

The crystal structure of IX viewed along the b axis is shown in Fig. 6.6. There is one molecule in an asymmetric unit of the P2i cell. The 2-ce group takes disordered structure with parallel conformations to the cobaloxime plane and is aligned along the 2i screw axis. The host amine with the disordered cycloheptyl group is also aligned along the other 2i screw axis. The crystal structure of X is isostructural to that of IX. 

The crystal of IX was irradiated with a xenon lamp for 2 weeks. The structure analyzed by X-rays indicated that the 2-ce group was isomerized to the 1-ce group with R and S configurations with retention of the single crystal form. The original 2-ce group was not observed in the electron density map after the irradiation. The occupancy factors of R and S enantiomers were 34.3 and 65.7 %. 

The photoproducts in the crystal after the irradiation were also analyzed by HPLC. The original cobaloxitne complex with the 2-ce group remained only by 3.6 %. The other 96.4 % of cobaloxime complex was transformed to the 1-ce complex with the 

Although the optical yields in the photoreactions of IX and X are not so good because the 2-ce group takes a disordered structure, the mechanism of the 2-ce to 1-ce isomerization was clearly made, hi order to control the reaction more precisely, the host amines should occupy the position surrounding the 2-ce group in the crystal structure. If the crystal with an ordered 2-ce group may be made, the photoisomerization would proceed with about 100 % reaction and optical yields in the crystalline state. 

---

A more eflicient and general synthetic procedure is the Masamune reaction of aldehydes with boron enolates of chiral a-silyloxy ketones. A double asymmetric induction generates two new chiral centres with enantioselectivities > 99%. It is again explained by a chair-like six-centre transition state. The repulsive interactions of the bulky cyclohexyl group with the vinylic hydrogen and the boron ligands dictate the approach of the enolate to the aldehyde (S. Masamune, 1981 A). The fi-hydroxy-x-methyl ketones obtained are pure threo products (threo = threose- or threonine-like Fischer formula also termed syn" = planar zig-zag chain with substituents on one side), and the reaction has successfully been applied to macrolide syntheses (S. Masamune, 1981 B). Optically pure threo (= syn") 8-hydroxy-a-methyl carboxylic acids are obtained by desilylation and periodate oxidation (S. Masamune, 1981 A). Chiral 0-((S)-trans-2,5-dimethyl-l-borolanyl) ketene thioketals giving pure erythro (= anti ) diastereomers have also been developed by S. Masamune (1986). 

A catalytic enantio- and diastereoselective dihydroxylation procedure without the assistance of a directing functional group (like the allylic alcohol group in the Sharpless epox-idation) has also been developed by K.B. Sharpless (E.N. Jacobsen, 1988 H.-L. Kwong, 1990 B.M. Kim, 1990 H. Waldmann, 1992). It uses osmium tetroxide as a catalytic oxidant (as little as 20 ppm to date) and two readily available cinchona alkaloid diastereomeis, namely the 4-chlorobenzoate esters or bulky aryl ethers of dihydroquinine and dihydroquinidine (cf. p. 290% as stereosteering reagents (structures of the Os complexes see R.M. Pearlstein, 1990). The transformation lacks the high asymmetric inductions of the Sharpless epoxidation, but it is broadly applicable and insensitive to air and water. Further improvements are to be expected. 

Non-enzymatic cyclizations of educts containing chiral centres can lead to products with additional "asymmetric centres. The underlying effect is called "asymmetric induction . Its systematic exploration in steroid syntheses started when G. Saucy discovered in 1971 that a chiral carbon atom in a cyclic educt induces a stereoselective Torgov condensation several carbon atoms away (M. Rosenberger, 1971, 1972). 

This reaction is a clear example of the importance of tautomeric equilibrium studies in this series since, to the extent that the starting thiazolone does not epimerize in the medium, asymmetric induction may be expected in this reaction (453, 455). 

There have been several reviews of asymmetric synthesis via chiral organoboranes (6,8,378,382,467—472). Asymmetric induction in the hydroboration reaction may result from the chiraHty present in the olefin (asymmetric substrate), in the reagent (asymmetric hydroboration), or in the catalyst (catalytic asymmetric hydroboration). 

High levels of asymmetric induction have been achieved in the hydroboration of 1,3-, 1,4-, and 1,5-dienes with thexylborane (482,483,489,490). The first chiral center is formed by an intermolecular reaction. In the second step, the organoborane intermediate undergoes an intramolecular hydroboration, creating the second chiral center with high diastereoselectivity. 

The addition of methylmagnesium iodide to 2-phenylpropanal is stereoselective in producing twice as much syn-3-phenyl-2-butanol as the anti isomer (entry 5). The stereoselective formation of a particular configuration at a new stereogenic center in a reaction of a chiral reactant is called asymmetric induction. This particular case is one in which the stereochemistry can be predicted on the basis of an empirical correlation called Cram s rule. The structural and mechanistic basis of Cramls rule will be discussed in Chapter 3. 

Under sonication conditions, the reaction of perfluoroalkyl bromides or iodides with zinc can be used to effect a variety of functionalization reactions [39, 40, 41, 42] (equation 30) Interestingly, the ultrasound promoted asymmetric induction with the perfluoroalkyl group on the asymmetric carbon was achieved by the reaction of perfluoroalkyl halides with optically active enamines in the presence of zinc powder and a catalytic amount of dichlorobisftc-cyclopenta-dienyl)titanium [42] (equation 31)... 

Chiral (salene)Ti(IV) complexes, TMSCN. This system is selective for aldehydes the asymmetric induction is dependent upon aldehyde struc-... 

Meyers has demonstrated that chiral oxazolines derived from valine or rert-leucine are also effective auxiliaries for asymmetric additions to naphthalene. These chiral oxazolines (39 and 40) are more readily available than the methoxymethyl substituted compounds (3) described above but provide comparable yields and stereoselectivities in the tandem alkylation reactions. For example, addition of -butyllithium to naphthyl oxazoline 39 followed by treatment of the resulting anion with iodomethane afforded 41 in 99% yield as a 99 1 mixture of diastereomers. The identical transformation of valine derived substrate 40 led to a 97% yield of 42 with 94% de. As described above, sequential treatment of the oxazoline products 41 and 42 with MeOTf, NaBKi and aqueous oxalic acid afforded aldehydes 43 in > 98% ee and 90% ee, respectively. These experiments demonstrate that a chelating (methoxymethyl) group is not necessary for reactions to proceed with high asymmetric induction. 

Asymmetric induction of radicals with neighboring ester fragment and 0-heterocyclic stereogenic center 98SL213. 

Remote asymmetric induction using chiral sulfoxides, derivatives of furan, thiophene, and pyrrole 98YGK798. 

Asymmetric induction by sulfoxide is a very attractive feature. Enantiomerically pure cyclic a-sulfonimidoyl carbanions have been prepared (98S919) through base-catalyzed cyclization of the corresponding tosyloxyalkylsulfoximine 87 to 88 followed by deprotonation with BuLi. The alkylation with Mel or BuBr affords the diastereomerically pure sulfoximine 89, showing that the attack of the electrophile at the anionic C-atom occurs, preferentially, from the side of the sulfoximine O-atom independently from the substituent at Ca-carbon. The reaction of cuprates 90 with cyclic a,p-unsaturated ketones 91 was studied but very low asymmetric induction was observed in 92. 

---