Transfer of chirality

In a chiral aldehyde or a chiral ketone, the carbonyl faces are diastereotopic. Thus, the addition of an enolate leads to the formation of at least one stereogenic center. An effective transfer of chirality from the stereogenic center to the diastereoface is highly desirable. In most cases of diastereoface selection of this type, the chiral aldehyde or ketone was used in the racemic form, especially in early investigations. However, from the point of view of an HPC synthesis, it is indispensable to use enantiomerically pure carbonyl compounds. Therefore, this section emphasizes those aldol reactions which are performed with enantiomerically pure aldehydes. 

The transfer of chirality from sulfur to carbon as well as the high stereoselectivity were explained by a preference of rearrangement through transition state 11a over lib due to steric interference between the p-tolyl and a-alkyl group. 

Chiral amines were always considered important targets for synthetic chemists, and attempts to prepare such compounds enantioselectively date back to quite early times. Selected milestones for the development of enantioselective catalysts for the reduction of C = N functions are listed in Table 34.1. At first, only heterogeneous hydrogenation catalysts such as Pt black, Pd/C or Raney nickel were applied. These were modified with chiral auxiliaries in the hope that some induction - that is, transfer of chirality from the auxiliary to the reactant -might occur. These efforts were undertaken on a purely empirical basis, without any understanding of what might influence the desired selectivity. Only very few substrate types were studied and, not surprisingly, enantioselectivities were... 

This method can be regarded as an example of memory of chirality,71 a phenomenon in which the chirality of the starting material is preserved in a reactive intermediate for a limited time. The example in Scheme 2-35 can also be explained by the temporary transfer of chirality from the a-carbon to the t-BuCH moiety so that the newly formed chiral center t-BuCH acts as a memory of the previous chiral center. The original chirality can then be restored upon completion of the reaction. 

Okamura and Yamada (2/7) were more successful when they performed the 1,3-transfer of chirality in a Pictet-Spengler reaction of methyl L-tryptophan and sodium 3-(3-methoxyphenyl)glycidate (389). Thus (35, 155, 20/ )-(-)-yohim-bone (305) has been prepared in optically pure form. 

Rearrangement of dienynols to vinylallene sulfoxides. A few years ago, Oka-mura et al. (11, 39) reported the rearrangement of a dienynol to an allenyldiene with transfer of chirality of the propargylic alcohol. This rearrangement has now been used for an enantioselective synthesis of a sesquiterpene, (+ )-sterpurene (3).Thus reaction of the optically active propargylic alcohol 1 with C6H,SC1 at 25° results in a vinylallene (a) that cyclizes to the optically active sulfoxide 2. Nickel-... 

From simple sugars to cyclic (non-sugar) derivatives transfer of chirality... 

There can be two kinds of chiral tin reagents tin chiral and C-chiral. Early reports of chiral tin hydride involved transfer of chirality via a chiral tin center [45-47]. These tin hydrides were prone to racemization. Thus, chiral carbon-based ligands attached to the tin center were synthesized to minimize racemization. The first chiral tin hydride containing a C2-symmetric binaphthyl substituent was reported by Nanni and Curran (Scheme 16) [48]. a-Bromoketone 58 was reduced by chiral tin hydride 59 (R3 = Me), where the reactivity and selectivity was dependent on the reaction conditions (entry 4). 

Although the Lewis acid greatly enhances the selectivity, the transfer of chirality is derived from the chiral ligand on the stannane. These deductions are supported by the fact that when stannane 67 is used, the ee of the product increases from 4% in the absence of a Lewis acid to 46% in the presence of achiral Lewis acid (Cp2ZrCl2) for substrate 63. When the enantiomer of 67 was used as the reductant, the product was obtained with the opposite configuration, which also supports the above-mentioned presumption. 

The Diels-Alder reaction outlined above is a typical example of the utilization of axially chiral allenes, accessible through 1,6-addition or other methods, to generate selectively new stereogenic centers. This transfer of chirality is also possible via in-termolecular Diels-Alder reactions of vinylallenes [57], aldol reactions of allenyl eno-lates [19f] and Ireland-Claisen rearrangements of silyl allenylketene acetals [58]. Furthermore, it has been utilized recently in the diastereoselective oxidation of titanium allenyl enolates (formed by deprotonation of /3-allenecarboxylates of type 65 and transmetalation with titanocene dichloride) with dimethyl dioxirane (DMDO) [25, 59] and in subsequent acid- or gold-catalyzed cycloisomerization reactions of a-hydroxyallenes into 2,5-dihydrofurans (cf. Chapter 15) [25, 59, 60],... 

Allene is a versatile functionality because it is useful as either a nucleophile or an electrophile and also as a substrate for cycloaddition reactions. This multi-reactivity makes an allene an excellent candidate for a synthetic manipulations. In addition to these abilities, the orthogonality of 1,3-substitution on the cumulated double bonds of allenes enables the molecule to exist in two enantiomeric configurations and reactions using either antipode can result in the transfer of chirality to the respective products. Therefore, the development of synthetic methodology for chiral allenes is one of the most valuable subjects for the synthetic organic chemist. This chapter serves as an introduction to recent progress in the enantioselective syntheses of allenes. Several of the earlier examples are presented in excellent previous reviews [ ] ... 

The efficiency of chirality transfer of chiral 2,3-allenic acids can be much increased by switching the Jt-allylpalladium mechanism to a coordinative cycliza-tion-reductive elimination route (Scheme 16.25) [30]. 

Tius and co-workers elegantly applied a variant of the Nazarov reaction to the preparation of cyclopentenone prostaglandins (Scheme 19.39) [46]. Moreover, it was demonstrated that the chirality of non-racemic allenes is transferred to an sp3-hybridized carbon atom. Preparation of allenic morpholinoamide 214 and resolution of the enantiomers by chiral HPLC provided (-)- and (+)-214. Compound (-)-214 was exposed to the vinyllithium species 215 to afford a presumed intermediate which was not observed but spontaneously cyclized to give (+)- and (—)-216 as a 5 1 mixture. Compound (+)-216 was obtained with an 84% transfer of chiral information and (-)-216 was obtained in 64% ee. The lower enantiomeric excess of (—)-216 indicates that some Z to E isomerization took place. This was validated by the conversion of 216 to 217, where the absolute configuration was established. The stereochemical outcome of this reaction has been explained by conrotatory cyclization of 218 in which the distal group on the allene rotates away from the alkene to give 216. 

V. ASYMMETRIC INDUCTION IN TRANSFER OF CHIRALITY FROM SULFUR TO OTHER CENTERS... 

In the last two decades optically active sulfur compounds have found wide application in asymmetric synthesis. This is mainly because organic sulfur compounds are quite readily available in optically active form. Moreover, the chiral sulfur groupings that induce optical activity can be removed from the molecule easily, under fairly mild conditions, thus presenting an additional advantage in the asymmetric synthesis of chiral compounds. This section deals with reactions in which asymmetric induction in transfer of chirality from sulfur to other centers was observed. This subject has been treated only in a cursory manner in recent reviews on asymmetric synthesis (290-292). 

The first example of asymmetric induction in transfer of chirality from the chiral sulfur atom to the prochiral carbon atom was described by Goldberg and Sahli in 1965 (197). It concerns the pyrolysis of the optically active p-tolyl tra s-4-methylcyclohexyl sulfoxides 258. It was found that on pyrolysis at 200 to 250°C, optically active sulfoxides (R)-258 and (5)-258 yield optically active 4-methylcyclohexenes-l 259, with the absolute R and S configurations, respectively, at the newly formed chiral carbon atoms (Scheme 25). The optical purities of the 4-methylcyclohexenes-l that were formed depended largely on the temperature of pyrolysis. Thus, the values of 42 and 70% optical purity were noted for 259 at 250° and 200°C, respectively. The formation of the cycloolefins 259, whose absolute configurations are the same as those of the starting optically active sulfoxides 258, indicates that the pyrolysis reaction proceeds... 

Another example of asymmetric induction in the transfer of chirality from tricoordinate sulfur to the nitrogen atom was reported by Kobayashi (157), who found that methylation of benzylethylani-line with (+)-methoxymethyl-p-tolylsulfonium salt 113 yields (-)-benzylethylmethylphenylammoniumtetrafluoroborate 268. A similar asymmetric methylation reaction was observed with benzyl ethyl sulfide. Chiral ammonium 268 and sulfonium salts 112 were formed... 

Organosulfur chemistry is presently a particularly dynamic subject area. The stereochemical aspects of this field are surveyed by M. Mikojajczyk and J. Drabowicz. in the fifth chapter, entitled Qural Organosulfur Compounds. The synthesis, resolution, and application of a wide range of chiral sulfur compounds are described as are the determination of absolute configuration and of enantiomeric purity of these substances. A discussion of the dynamic stereochemistry of chiral sulfur compounds including racemization processes follows. Finally, nucleophilic substitution on and reaction of such compounds with electrophiles, their use in asymmetric synthesis, and asymmetric induction in the transfer of chirality from sulfur to other centers is discussed in a chapter that should be of interest to chemists in several disciplines, in particular synthetic and natural product chemistry. 

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