Chirality Mislow

Racemic [l-(4-methylphenylsulfinyl)-2-propenyl]lithium, prepared with lithium diiso-propylamide in THF, adds to racemic chiral 2-methylalkanals with good a- and syn selectivity114, us Qn heating with trimethyl phosphite or triethylamine, the major isomer furnishes the ( )-.yvn-2-alkene-l,4-diol by Mislow rearrangement1 lb. 

In order to account for the unusually facile thermal racemization of optically active allyl p-tolyl sulfoxide (15 R = p-Tol) whose rate of racemization is orders of magnitude faster than that of alkyl aryl or diaryl sulfoxides as a result of a comparably drastically reduced AH (22kcalmol- ), Mislow and coworkers44 suggested a cyclic (intramolecular) mechanism in which the chiral sulfoxide is in mobile equilibrium with the corresponding achiral sulfenate (equation 10). 

Following Wilkinson s discovery of [RhCl(PPh3)3] as an homogeneous hydrogenation catalyst for unhindered alkenes [14b, 35], and the development of methods to prepare chiral phosphines by Mislow [36] and Horner [37], Knowles [38] and Horner [15, 39] each showed that, with the use of optically active tertiary phosphines as ligands in complexes of rhodium, the enantioselective asymmetric hydrogenation of prochiral C=C double bonds is possible (Scheme 1.8). 

Desymmetrization, which refers to a process of efficiently desymmetrizing maw-molecules or achiral molecules to produce chiral ones, is a versatile method for preparing chiral nonracemic molecules.90 Desymmetrization of meso-compounds generally leads to the formation of a C-C or a C-X (X is a hetero atom) bond. The reaction normally uses a functional group residing on the symmetric element (in most cases the C2 axis or a plane) to differentiate two (or more) symmetrically equivalent functionalities elsewhere within the substrate molecule. This work was first reported by Hoye et al.91 and Mislow and Siegel92 in 1984. 

An early application was to the pathway for conformational isomerization of molecules Ar3Z, with three aromatic rings on the same centre (Mislow, 1976). Typically the system is pyramidal (tetrahedral overall where there is a fourth substituent on Z), and the rings are close enough in space that they cannot rotate independently about the Z-Ar bond. Triphenylphosphine oxide, to take a specific example, crystallizes in a propeller conformation [4 Z = P=OJ which is chiral, with all three benzene rings rotated in the same sense from the relevant C-P-O plane. A study (Bye et al., 1982) of deformations from this geometry for more than 1000 related structures in various environments allowed a detailed description of the pathway for... 

Roald Hoffmann, personal correspondence, letter of October 16, 1990. Also, R. Hoffmann, "Nearly Circular Reasoning," American Scientist, 76 (1988) 182185. And see Kurt Mislow and Paul Bickart, "An Epistemological Note on Chirality," Israel Journal of Chemistry 15 (197677) 16 "Thus chiral and achiral are used with two different connotations When the terms are applied to a geometric model, they are sharply defined, whereas when used in conjunction with observables, they necessarily entail a certain fuzziness" (6). 

Mislow, Kurt, and Paul Bickart. "An Epistemological Note on Chirality." Israel Journal of Chemistry, 15 (19761977) 16. 

The existence of achiral conformations in the ensemble is no prerequisite for its achirality. K. Mislow et a/.20a> synthesized an achiral diphenyl derivative with orthogonal benzene rings which carry in their p-positions chiral residues with the same chemical constitution but opposite configuration and observed achirality although none of the conformations is itself achiral. Here achirality is attributed to the fact that the molecule... 

According to this correlation model, in which the principles of steric control of asymmetric induction at carbon (40) are applied, the stereoselectivity of oxidation should depend on the balance between one transition state [Scheme 1(a)] and a more hindered transition state [Scheme 1(6)] in which the groups and R at sulfur face the moderately and least hindered regions of the peroxy acid, respectively. Based on this model and on the known absolute configuration of (+)-percamphoric acid and (+)-l-phenylperpropionic acid, the correct chirality at sulfur (+)-/ and (-)-5 was predicted for alkyl aryl sulfoxides, provided asymmetric oxidation is performed in chloroform or carbon tetrachloride solution. Although the correlation model for asymmetric oxidation of sulfides to sulfoxides is oversimplified and has been questioned by Mislow (41), it may be used in a tentative way for predicting the chirality at sulfur in simple sulfoxides. 

Jacobus and Mislow (85) reported that racemic benzenesulfinyl chloride reacts with chiral jV-methyl-2-phenylpropylamine to yield a mixture of the corresponding diastereomeric sulfinamides 76 that can be separated into pure components by fractional crystallization. 

Andersen (75,76), as well as Mislow (221), discovered that the ORD curves of alkyl aryl sulfoxides show a strong Cotton effect in the region below 250 nm. An extensive study by Mislow and his coworkers (47) led to the following empirical rules, correlating the sign of the Cotton effect with the absolute configurations of chiral dialkyl, alkyl aryl, and diaryl sulfoxides, as well as menthyl esters of aromatic sulfinic acids ... 

The most frequently encountered reactions in organic sulfur chemistry are nucleophilic displacement reactions. The mechanism and steric course of reactions have been the main points of interest of research groups all over the world, in particular, Andersen, Cram, Johnson, and Mislow in the United States Kobayashi and Oae in Japan Kjaer in Denmark and Fava and Montanari in Italy. The results of these investigators have been discussed exhaustively in many reviews on sulfur stereochemistry. In a recent report on nucleophilic substitution at tricoordinate sulfur, the literature was covered by Tillett (10) to the end of 1975. Therefore only some representative examples of nucleophilic substitution reactions at chiral sulfur are discussed here. However, recent results obtained in the authors laboratory are included. 

Tertiary carbon atoms along the chain have been defined as asymmetric (22-25, 34-37), pseudoasymmetric (6, 10, 38-40), stereoisomeric centers (30, 31), and diasteric centers (41). The first two terms put the accent on chirality and are linked to the use of models of finite and infinite length, respectively the last two consider only phenomena of stereoisomerism. Note the relationship between these last definitions and Mislow s and Siegel s recent discussion (42), where the two concepts—stereoisomerism (or stereogenicity) and chirality—are clearly distinguished. The tertiary carbon atoms of vinyl polymers are always stereogenic whether they are chinotopic or achirotopic (42) depends on stmctural features and also on the type of model chosen (43). 

Mislow and Bickart (258) have recently discussed the properties, and specified the limitations and essential features, of models that can be used for the prediction of chirality of a molecular system. In the simplified and idealized representation of molecular stracture, nonessential features are deliberately left out the model summarizes some selected aspects of the system and completely disregards or even falsifies, others. The model must be adequate to the time scale in which the phenomenon is observed. In particular, in mobile conformational systems it should refer to a time-averaged structure. In other words, the model can have a higher symmetry than that observed under static conditions (e.g., by X-ray diffraction in the crystalline state or by NMR under slow exchange conditions) (259). 

Mezey, P. G. (1998) Mislow s label paradox, chirality-preserving conformational changes, and related chirality measures. Chirality 10, 173-179. 

Moscowitz, A., Mislow, K. J. Am. Chem. Soc. 84, 4605 (1962). Although they follwed the axial instead of planar chirality convention in their R,S-specification for chiral (rans-cyclooctene, both procedures give the same R,S-notation in this case. 

K. Mislow and J. Siegel have recently completed a very elaborate and fascinating paper on The Theoretical Foundation of Factorization in Stereochemistry which advances a scheme for a novel classification of chiral structures and abandons the concept of axial and planar chirality. The contents of this work can, however, not be discussed in this survey. 

Stimulating discussion with several colleagues, especially Profs. F. A. L. Anet (UCLA), K. Mislow (Princeton), M. Nakazaki (Osaka) and V. Prelog (Zurich), to whom I am very grateful, have clearly revealed that the subject of planar chirality is still or again a topic of some controversy. This has been demonstrated e.g. in the paper by K. Mislow and J. Siegel (see footnote 2 on p. 30) a preprint of which has been kindly submitted to me by Prof. K. Mislow. 

MFor discussions of the relationship between a chiral carbon and chirality, see Mislow Siegel J. Am. Chem. Soc. 1984, 106, 3319 Brand Fisher J. Chem. Educ. 1987, 64, 1035. 

Using this theorem we can prove that various molecular graphs are intrinsically chiral. We shall illustrate by proving that the graphs of a ferrocenophane derivative molecule [26] and the Simmons-Paquette molecule [29, 30] are both intrinsically chiral. (Note that Liang and Mislow observed the intrinsic chirality of this ferrocenophane derivative as well as many other molecules [21].)... 

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