Dissymmetric allenes

Reactions with Prochiral Ketenes to give Dissymmetric Allenes... 

The allenes are another example of compounds which show molecular asymmetry if both ends are dissymmetric. 

The propynyl Claisen rearrangement constitutes a powerful method for the regio- and diastereoselective synthesis of chiral allenes containing an additional stereogenic center in one of the substituents at the axially dissymmetric propadiene unit. 

The cyclobutane 5 obtained from 1,1 -difluoroallene comes about from dissymmetrical head-to-tail dimerization, while the head-to-head dimer, formed in equal amounts, preferentially reacts further to give oligomers and polymers.25 Both eyclobutanes 4 and 5 have been previously reported (see Houben-Weyl, Vol. 4/4, pp 156 157) from different allene precursors. 

Allen et at. found that high yields of the dissymmetric trans-2,3-diaryloxirans result from the reaction between semistabilized arsonium ylides derived from the benzyl salts of the enantiomers of racemic o-phen-ylenebismethyl phenylarsine and of methyl a-naphthyl-p-tolylarsine upon reaction with prochiral aromatic aldehydes. Optical yields of between 4.7 and 38% are obtained using optically active arsonium salts (2). 

This is not strictly true. There are some special (and rare) classes of molecules that are chiral because of restricted rotation around single or double bonds that impose a nonplanar and chiral conformation. Substituted allenes are the classic example of axially dissymmetric chiral molecules. 

When the chiral allenic amine 1 was cyclized using silver tetrafluoroborate, transfer of chirality occurred from the allenic moiety to the C-2 stereogenic center, as determined by conversion of 2 into the diastcrcomeric mixture of the (+)-(5)-0-methylmandelic amides of the debenzylated product. The high asymmetric induction was ascribed to the formation of a dissymmetric silver-allene complex229. 

Molecules that do not possess an asymmetric center may still have nonsuperimposable mirror images and exist as enantiomers. These molecules contain a chiral plane or chiral axis and are dissymmetric with respect to either that plane or axis. The structures of the enantiomers of the sedative-hypnotic methaqualone are presented in Fig. 4. In this molecule there is a chiral axis between the nitrogen atom (N-1) and phenyl ring (C-1). The dissymmetry of the two forms of the molecule is a result of hindered rotation around this axis, which is due to steric interactions between methyl groups (M-1 and M-2). Other axially dissymmetric molecules include allene, biaryls, alkylidenecyclohexanes, and spiranes. Planar dissymmetric molecules are exemplified by molecules such as tra s-cycloalkenes. 

Finally it should be mentioned that most Claisen rearrangements are also possible with propargylvinyl systems leading to allenic derivatives, and very often providing efficient syntheses of functionalized lenes. From a stereochemical point of view such an approach is of special interest as it oriers the opportunity of transferring chirality from a centrodissymmetric compound to an axial dissymmetric one. A rare application in synthesis is depicted in equation (42). ... 

Asymmetric and enantioselective olefination reactions continue to be of interest. Wadsworth-Emmons reactions of 4-substituted cyclohexanones with the phosphonate (147), which carries a chiral benzopyrano-isoxazolidine substituent, proceed with diastereomeric excesses of 80-90% and hence provide another example of such an approach to enantiomerically pure, axially dissymmetric cyclohexylidene derivatives. A further example of trapping of in situ generated ketenes by Wadsworth-Emmons reactions to give allene carboxylates has been reported and the reaction has been extended to enantioselective synthesis by use of the optically active phosphonates (148) (Scheme 14). Moderate to good chemical yields and e.e. values up to 84% were obtained depending on the nature of (148) and the reactions conditions. 

Chirality about an axis is exemplified by allenes, such as the 2,3-penta-diene enantiomer 23. In 23 the methyl and hydrogen substituents on C2 lie in a plane (in the page) that is perpendicular to the plane containing the methyl and hydrogen substituents on C4. Here the axis of chirality is coincident with the C2—C3—C4 bond axis. The structure has a C2 symmetry element, so it is dissymmetric, not asymmetric. The C2 rotation axis is perpendicular to the axis of chirality, as illustrated in Figure 2.13. It must be emphasized that not all structures that are chiral about an axis have a C2 rotation axis. For example, the 2,3-hexadiene enantiomer 24 also has an axis of chirality coincident with the C2-C3-C4 bond axis, but it does not have a C2 rotation axis. The adamantane 25 and appropriately substituted spiro compounds, such as 26, are also chiral about an axis. ... 

Chirality may exist in many molecules that do not possess a chiral center. Such compounds may possess a chiral plane or a chiral axis, and are said to be dissymetric with respect to either that plane or that axis. Certain optically active allenes, biaryls, alkylidenecyclohexanes, and spiranes provide examples of axially dissymmetric molecules (chiral axis), irons-Cycloalkenes exemplify planar dissymmetry in molecules. The configurations of these classes may be specified by the Cahn-Ingold-Prelog convention using the usual R and 5 descriptors. Special subrules, which we will not describe here, are applied to this purpose. The interested reader is referred to references 8 (see p. 43) and 9 for details. Scheme 2.1 presents some molecules that are optically active because of planar or axial dissymmetry, and for which the absolute configurations have been determined. 

An alternative means of resolution depends on the differences in rates of reactions of enantiomers with a chiral reagent. The transition state energies for reaction of one chiral molecule with another can be different for each enantiomer. If a racemic mixture R molecule -h 5 molecule) reacts with an optically active reagent (R reagent), the two transition states R molecule / reagent) and (5 molecule i reagent) bear a diastereomeric relationship to each other. Kinetic resolution is the term used to describe the separation of enantiomers by selective reaction with an optically active reagent. A very useful application of this technique is the resolution of allenes by preferential reaction of one enantiomer with an optically active borane. Hydroboration of the allenes occurs at different rates, and the reaction mixture becomes enriched in the less reactive enantiomer. An allene that has been partially resolved by this technique was presented as an example of an axially dissymmetric molecule in Scheme 2.1 68 entry 2,1,3-dimethylallene). ... 

The generation of dissymmetric non-racemic 1,2-dienes, i.e. allenic compounds, from the corresponding ketene 6, was investigated in 1975 using optically active phosphinate-type esters such as 7 incorporating a stereogenic phosphorus center [21]. Although neither the chemical nor the optical yields of allenic products such as 8 were wholly satisfactory (41-80% yield and up to 23% ee), this is the only example of the use of a phosphinate ester in asymmetric olefination. 

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