Planar chiral compounds

Related chemistry has been reported by Snieckus using ferrocene-carboxamides with sparteine as additive, giving planar chiral adducts in excellent ees (up to 99%) [62]. 

---

Whereas a center or an axis of chirality can by clearly defined 2> 7) there is still some ambiguity in respect to the specification of a plane of chirality. It therefore seems somewhat difficult to define the scope of planar chiral compounds which at a first glance include mostly rather rigid aromatic compounds of special interest from synthetic, structural, spectroscopic and especially chiroptical points of view. 

The development of ferrocene 9 was part of our studies on planar-chiral compounds, which also involved the synthesis of other scaffolds such as chromium-tricarbonyl arenes [15], sulfoximidoyl ferrocenes [16], and [2.2]paracyclophanes [17]. In aryl transfer reactions, however, ferrocene 9 proved to be the best catalyst in this series, and it is still used extensively today. 

Compared with asymmetric ethylation, reports on asymmetric phenylation are limited. We disclosed the enantioselective phenylation using diphenylzinc prepared in situ from phenyl Grignard reagent and zinc chloride. This method needs a stoichiometric amount of chiral amino alcohol DBNE 18 but good ee of 82% was achieved [32], A catalytic phenylation was examined using planar chiral compound 1 based on ferrocene, and chiral diaryl carbinols of moderate ee were provided from diphenylzinc and 4-chlorobenzaldehyde (Scheme 10) [33]. A catalytic and highly enantioselective phenylation was realized by binaphthyl-based chiral catalyst 23. In this reaction, the addition of 2 equivalents of diethyl-zinc against catalyst increases the yield and ee [34]. Recently, chiral amino alcohol DPMPM 9 was also reported to be an efficient catalyst for asymmetric phenylation [35]. 

Note It may prove tedious to separate the individual enantiomers from the racemic mixture of the planar chiral compounds formed. 

The compounds obtained by the resolution procedures can often directly be used as chiral auxiliaries, but sometimes it is necessary to convert them to other products, e.g., planar chiral compounds. Frequent functional group transformations are summarized in Sections 4.3.3 and 4.3.3.2. The link to planar chiral compounds is described in Sections 4.3.3.3 and 4.4.1. 

In addition to stereoselective metalation, other methods have been applied for the synthesis of enantiomerically pure planar chiral compounds. Many racemic planar chiral amines and acids can be resolved by both classical and chromatographic techniques (see Sect. 4.3.1.1 for references on resolution procedures). Some enzymes have the remarkable ability to differentiate planar chiral compounds. For example, horse liver alcohol dehydrogenase (HLADH) catalyzes the oxidation of achiral ferrocene-1,2-dimethanol by NAD to (S)-2-hydroxymethyl-ferrocenealdehyde with 86% ee (Fig. 4-2la) and the reduction of ferrocene-1,2-dialdehyde by NADH to (I )-2-hydroxymethyl-ferrocenealdehyde with 94% ee (Fig. 4-2lb) [14]. Fermenting baker s yeast also reduces ferrocene-1,2-dialdehyde to (I )-2-hydroxymethyl-ferro-cenealdehyde [17]. HLADH has been used for a kinetic resolution of 2-methyl-ferrocenemethanol, giving 64% ee in the product, (S)-2-methyl-ferrocenealdehyde... 

Planar chiral compounds should also be accessible from the chiral pool. An example (with limited stereoselectivity) of such an approach is the formation of a ferrocene derivative from a -pinene-derived cyclopentadiene (see Sect. 4.3.1.3 [81]). A Cj-symmetric binuclear compound (although not strictly from the chiral pool, but obtained by resolution) has also been mentioned [86]. Another possibility should be to use the central chiral tertiary amines derived from menthone or pinene (see Sect. 4.3.1.3 [75, 76]) as starting materials for the lithiation reaction. In these compounds, the methyl group at the chiral carbon of iV,iV-dimethyl-l-ferrocenyl-ethylamine is replaced by bulky terpene moieties, e.g., the menthane system (Fig. 4-2 le). It was expected that the increase in steric bulk would also increase the enantioselectivity over the 96 4 ratio, as indicated by the results with the isopropyl substituent [118]. However, the opposite was observed almost all selectivity was lost, and lithiation also occurred in the position 3 and in the other ring [134]. Obviously, there exists a limit in bulkiness, where blocking of the 2-position prevents the chelate stabilization of the lithium by the lone pair of the nitrogen. 

Therefore, the above reaction path provides a convenient way of preparing helical-(planar-) chiral compounds, which show interesting circulardichroisms [45, 153]. These results contribute to a better understanding of the relation between structure and chiroptical properties [153, 154],... 

Planar chiral compounds usually (and for the purpose of this review, always) contain unsymmetrically substituted aromatic systems. Chirality arises because the otherwise enantiotopic faces of the aromatic ring are differentiated by the coordination to a metal atom - commonly iron (in the ferrocenes) or chromium (in the arenechromium tricarbonyl complexes). Withdrawal of electrons by the metal centre means that arene-metal complexes and metallocenes are more readily lithiated than their parent aromatic systems, and the stereochemical features associated with the planar chirality allow lithiation to be diastereoselective (if the starting material is chiral) or enantioselective (if only the product is chiral). 

Scheme 5.29 Pd-catal)rzed intramolecular arylation to synthesize planar chiral compounds reported hy several groups.

The absolute configuration of axially chiral compounds can alternatively be specified by M and P which also apply to planar chiral compounds see reference [1],... 

Figure 4.3a shows a mono-substituted-[ ]paracyclophane as a typical planar-chiral compound. ... 

SchlogI, K., Widhalm, M., Vogel, E., Schwamborn, M. Stereochemistry of planar chiral compounds, IX. Chromatographic separation into enantiomers, chiroptic properties and relative configurations of 1,6-methano-[10]anulenes and 2,7-methano[10]azaanulenes. 

---