Paracyclophanes, chirality

Grimme S, Pischel I, Laufenberg S, Vogtle F (1998) Synthesis, structure, and chiroptical properties of the first 4-oxa[7]paracyclophane. Chirality 10 147-153... 

Optical Activity Caused by Restricted Rotation of Other Types. Substituted paracyclophanes may be optically active and 25, for example, has been resolved. In this case, chirality results because the benzene ring cannot rotate in such a way that the carboxyl group goes through the alicyclic ring. Many chiral layered cyclophanes (e.g., 26) have been prepared. ... 

Gade and Bellemin-Laponnaz have reported the synthesis, in good yields, of chiral oxazoline-imidazoliums salts 10a (Scheme 8) obtained by reaction of 2-bromo-4(S)-t-butyl oxazoline with several mono-N-substituted imidazoles [16]. Similaly an imidazolium salt 10b bearing a paracyclophane substituent was prepared by Bolm [17]. 

In 2004, Bolm et al. reported the use of chiral iridium complexes with chelating phosphinyl-imidazolylidene ligands in asymmetric hydrogenation of functionalized and simple alkenes with up to 89% ee [17]. These complexes were synthesized from the planar chiral [2.2]paracyclophane-based imida-zolium salts 74a-c with an imidazolylidenyl and a diphenylphosphino substituent in pseudo ortho positions of the [2.2]paracyclophane (Scheme 48). Treatment of 74a-c with t-BuOLi or t-BuOK in THF and subsequent reaction of the in situ formed carbenes with [Ir(cod)Cl]2 followed by anion exchange with NaBARF afforded complexes (Rp)-75a-c in 54-91% yield. The chela-... 

Some other enantioselective approaches have been attempted, still with moderate enantioselectivities, by making use of in situ systems containing a chiral NHC precursor. Luo and co-workers reported on the use of the bidentate chiral imidazo-lium salt 16, derived from L-proUne, in combination with [RhCia-COCcod)], leading to an enantiometic excess of around 20% [30]. The use of chiral imidazolium salt 17 in combination with [RhCl(CH2=CHj)j]j by Aoyama afforded slightly better ee (Fig. 7.3) [31 ]. So far, Bohn and co-workers have obtained the best enantioselectivities (up to 38% ee) for the catalytic addition of phenylboronic acid to aromatic aldehydes by using planar chiral imidazolium salts 18, derived from paracyclophane, in combination with [Rh(OAc)2]2 [32]. 

In order to study the role of the [2.2]paracyclophane-type planar chirality in asymmetric induction, Hou et al. have developed the synthesis of novel S/N-... 

Vogtle et al. have prepared chiral poly(imine) dendrimers of various generations by condensation of non-racemic 5-formyl-4-hydroxy[2.2]paracyclophane moieties with poly(amine) dendrimers [71]. They have found that the optical activity of these dendrimers was nearly constant with increasing generation number. 

The substance 4,12-dibromo[2.2]paracyclophane is the key intermediate en route to several functional C2-symmetric planar-chiral 4,12-disubstituted[2.2]paracydo-phanes. Braddock and coworkers have shown that this important intermediate can be obtained by microwave-assisted isomerization of 4,16-dibromo[2.2]paracydo-phane, itself readily prepared by bromination of [2.2]paracyclophane (Scheme 6.88) [182], By performing the isomerization in N,N-dimethylformamide as solvent (microwave heating at 180 °C for 6 min), in which the pseudo-para isomer is insolu-... 

Recently, carbene-oxazoline catalysts 33 and carbene-phosphine catalysts 34 (Fig. 29.19) with a chiral paracyclophane backbone have been synthesized and used to hydrogenate a variety of alkenes, with modest selectivity [41]. 

It is expedient in the case of chiral derivatives of [2.2]paracyclophane to number the atoms independently of absolute configuration and in such a way that substituents have the lowest possible numbers. Absolute configuration is then indicated by adding the prefix R or S. Cf. 

Thus, a slight enantiomeric imbalance in compounds induced by CPL was correlated for the first time to an organic compound with very high ee by asymmetric autocatalysis with amplification of chirality. Moreover, various chiral organic compounds such as 1,1-binaphthyl,[2.2]paracyclophanes, and primary alka-nols due to deuterium substitution have been found to serve as chiral triggers in asymmetric autocatalysis. 

Pye and Rossen have developed a planar chiral bisphosphine ligand, [2.2]PHANE-PHOS, based on a paracyclophane backbone (Scheme 1.6) [69]. Moreover, the ortho-phenyl substituted NAPHOS ligand, Ph-o-NAPHOS, has been successfully applied for the rhodium-catalyzed hydrogenation of a-dehydroamino acid derivatives [70]. 

Fig. 1. Plane of Chirality Enantio-morphous figures and corresponding torsional angles A—X—Y—Z 7). Molecular examples ([n]paracyclophane, [2.2]meta-cyclophane, bridged[10]anulene and ( )-cyclooctene) with descriptors (/ , S)...

Obviously carboxy derivatives such as 11-19 are simple chiral structures suitable for optical resolutions through diastereomeric salts. For this purpose carboxylic groups have been introduced into [10]- and [8]paracyclophane either by chloro-methylation and oxidation of the carboxaldehydes obtained thereof 39,44) or by lithiation and subsequent carboxylation40). Electrophilic substitution of strained paracyclophanes is not advisable since it may initiate rearrangement to the more stable metacyclophanes. Carboxy[7]paracyclophane (72) was first prepared in 1972 by ring contraction of a diazoketone derived from 4-carboxy[8]paracyclophane (75) 45). 

Again a carboxylic acid (23) was the first representative of optically active (and hence chiral) [2.2]paracyclophanes and related [m.n]homologues thereby proving the... 

By a reaction sequence similar to the one outlined above for the [8][8]cyclophane 32 also the levorotating [8][10]paracyclophane 33 was obtained starting from (—)-methyl[10]paracyclophanecarboxylic acid IS6. Opposite Cotton effects of (+)-32 and (—)-33 indicated that they had opposite chiralities, and hence it followed that both (+)-32 and (+)-33 had the same chirality, namely (S). It should be noted that for (-)-14 the chirality (S) had been established 40) (cf. also Ref.62) and sections 2.9.2. and 2.9.3.) it would be somewhat surprising that its levorotatory methyl derivative 15 had (/ ) chirality as deduced from the above sequence (—)-15 - (-)(/ )-33 44). Moreover, for levorotatory [m][n]paracyclophanes (S)chirality had been proposed by application of a sector rule 63) (see also 2.9.4.). 

Ingenious approaches have been developed for the syntheses of multi-layered [2.2]-paracyclophanes and especially for optically active representatives with known chiralities. For such gyrochiral structures with C2- or Z>2-symmetry the genetic name [n]chochins was proposed (meaning an oldfashioned Japanese lantern)64) where n represents the number of layers. Parts of their chemistry have been reviewed17). 

Optically active chochins were prepared by the Hofmann route 641 starting from (i )(—)-4-methyl[2.2]paracyclophane (38) with known chirality 54,67) (see 2.9.). Introduction of the trimethyl-ammoniomethyl group (via acetylation and subsequent transformations) afforded (—)-39 which was then cross-coupled with the ammonium base 36 to give a mixture of [2.2]paracyclophane and the levorotatory[3] and [4]chochins (40,43) with ( )-chirality in these cases the descriptors (/ ) and (5) specify the planar chirality of the inner rings(s) as shown in Fig. 2, in accordance with the rules presented in Section 1.2. 

Another approach to the construction of optically active chochins of known chirality — the so-called chiral recognition principle — involves the coupling of the optically active [2.2]paracyclophane derivative (R)-46 16) with the racemic mixture of the [3]chochm derivative 47. From the two diastereomeric [5]chochins which could be expected thereof, the one with (J )(S)(S)-chirality (see Fig. 2) because of eclipsed steric interactions is thermodynamically less stable than the (R)(R)(R)-isomer with Z)2-symmetry. The latter (44) was indeed the only product isolated from... 

Triple layered paracyclophanes such as 48 and 4968K the furano and thiopheno-phanes SO and 51 69), the triplelayered [3.3]paracyclophane 52 70) or [2.2]naphthaleno-phane 52a 70a) are further examples, but so far no optical resolutions of the chiral structures seem to have been described. 

For [2.2]paracyclophane-4-carboxylic acid (25) as (—)(R) This result has been mentioned in a footnote in Ref. 1011 but seems never to have been published (see also Ref. 61). The chirality of this acid was correlated via its ( )-aldehyde with a levo-rotatory hexahelicene derivative which, according to the paracyclophane moiety at the terminal, had to adopt (A/)-helicity. Its chiroptical properties are comparable to those of hexahelicene itself101. For the (—)-bromoderivative of the latter the (A/)-helicity was established by the Bijvoet-method 102). In a later study, (—)para-cyclophane-hexahelicene prepared from (—)-l,4-dimethylhexahelicene with known chirality (which in turn was obtained with approximately 12% enantiomeric purity by asymmetric chromatography) confirmed these results. It should be mentioned that [2.2]paracyclophane-4-carboxylic acid (25) was the first planar chiral cyclophane whose chirality was determined 1041 (see also Ref.54 ). The results justmentioned confirmed the assignment (+)( ). 

The known chirality of 23 and of the corresponding methyl derivative 38 has served as the basis for several configurational assignments especially for [m][n]44) and layered [2.2]paracyclophanes 64 as well as for the interpretation of rearrangement reactions to optically active [2.2]metaparacyclophanes 95 and for other stereochemical investigations 57 103) (see 2.6 and 2.8). 

The chirality of [2.2]paracyclophane derivatives has been deduced as being (—)(R) on the basis of the exciton theory of coupled oscillators 67) and confirmed by experimental results (see 2.9.1 and 2.9.3). In these compounds a negative Cotton effect at 270 nm (corresponding to the p-band) seems to be specific for the (R)-chirality 54). 

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