Stereochemical planar chirality

STEREOCHEMICAL TERMINOLOGY, lUPAC RECOMMENDATIONS Planar chirality,... 

M-), (P-) Stereochemical descriptors (M = minus, P = plus) introduced to describe the chirality of helical molecules. Extension of the CIP system to planar chirality gave an alternative description aR/aS for helical molecules such as helicenes, aR invariably = (M) and aS = (P), but for compounds showing planar chirality the reverse, with pR = (P) and pS = (M). Best avoided. See Section 7.3.2. 

Fig. 4-2. Planar-chiral and central-chiral stereochemical descriptors for 2-methyl-ferrocenecar-boxylic acid.

Ugi has coined the term stereorelating synthesis for the sequence lithiation/reac-tion with electrophiles [62,118], and used this technique as a method for the chemical correlation of the structure and for the determination of the enantiomeric purity of many 1,2-disubstituted ferrocene derivatives obtained either by resolution or by asymmetric synthesis (for a compilation, see [118]). It is important to note that all stereochemical features discussed above for central chiral compounds, such as retentive nucleophilic substitution, remain valid when more substituents are present at the ferrocene ring and the conversion of functional groups in planar chiral ferrocenes can be achieved by the same methods as described. 

Subsequently, better ligands than 44 have been designed for the asymmetric palladium-catalyzed reaction of 1,3-diphenylallyl acetate with sodium mal-onate. Both the bis-(phosphaferrocene) 48 synthesized as shown in Eq. (32) [77] and the phosphaferrocene-oxazolines 49 [78] perform this condensation with much higher ees (79% in the first case and up to 82% in the second case). In the second case, the stereochemical outcome of the reaction is determined by the planar chirality at the phosphaferrocene, rather than the chirality of the oxazo-line [78] ... 

A striking difference between the variable temperature NMR spectra of 14 and of 15-17 is observed. Although, in the heteroleptic diorganotin(II) compounds 15-17 coalescence occurs for the diastereotopic NMe2 resonances, the AB pattern of the benzylic methylene resonances remains intact up to +120° C (the highest temperature studied). This points to a process involving Sn—N dissociation, while the Sn lone pair remains stereochemically active and rotation around the Cjp —Sn bond is blocked. (Fast rotation around this bond would give rise to loss of the planar chirality and thus would render the diastereotopic benzylic methylene resonances homotopic.)... 

Similarly, chromium-complexed benzylic cations are also stabilized and organic reactions based on the benzylic cation species have been developed. For example, planar chiral o-substituted benzaldehyde dimethylacetal chromium complexes 4 were treated with 3-buten-l-ol in the presence of TiCl4 to give tet-rahydropyran derivatives with high diastereoselectivity (Eq. 5) [5]. The chromium-complexed benzylic oxonium ion 6 would be also generated and subsequent intramolecular cyclization afforded the cyclization product 7. Furthermore, the chromium-complexed benzyl alcohol derivative having electron-rich arene ring at the side chain produced tetrahydroisoquinoline skeleton by treatment with Lewis acid with stereochemical retention at the benzylic position (Eq. 6) [6]. 

Abstract Planar-chiral ri -arene-Cr(CO)3 complexes represent highly valuable buUdlng blocks for the dlastereo- and enantloselectlve synthesis of complex natural products and related bloactlve compounds. Highly original and competitive overall syntheses of various classes of natural products, such as sesquiterpenes, diterpenes, alkaloids and compounds with axial chirality, have been developed. In certain cases, the whole strategy is based on arene chromium chemistry and the various chemical and stereochemical effects of the metal unit are exploited In several subsequent transformations. Cationic Cp-ruthenium complexes allow arylether formation by Sj Ar reactions and have found application in the synthesis of glyco-peptide antibiotics. 

As demonstrated by Schmalz and coworkers, arene chromium chemistry offers unique and highly efficient entries to the aglycones of such compounds. The most successful approach [25, 26] follows the retrosynthetic analysis shown in Scheme 6, where the pseudopterosin aglycone (31) derives from a seco-com-pound of type 32. Such intermediates can be traced back (via 33) to the planar-chiral complex 34 carrying the absolute stereochemical information. 

The overall synthesis (Scheme 7) is in excellent competition in terms of yield and selectivity. The expenditure connected to the (stereoselective) introduction of the metal fragment in the beginning pays off tremendously, as both the chemical and stereochemical effects of the Cr(CO)3 unit are exploited in several key transformations. Actually, all new (lasting) stereocenters are established with virtually complete diastereoselectivity under the influence of the planar-chiral complex substructure. 

This synthesis is remarkable because mayor parts of it are carried out at the Cr(CO)3-complexed ligand and several new bonds are formed with high diaster-eoselectivity under the stereochemical influence of the planar-chiral n-complex moiety. The chiral building block 80 is obtained in enantiomerically pure form either by resolution (via imine formation with 1-valinol) or by diastereoselective complexation of a chiral cyclic aminal according to the procedure of Alexakis... 

The development of novel chiral metal complexes and chiral ligands is crucial for both progress and development of asymmetric catalytic synthesis [1-3]. Within this area, the appearance of planar-chiral ferrocenes as ligands in asymmetric catalysis has been an important advancement [4-7]. While most of these complexes bear side chains or atom groups with stereogenic centres, it is often the 1,2-disubstitution pattern of the n-complexed ring that creates an inherent planar chirality [8] and exercises efficient stereochemical control. 

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). 

As with atropisomeric biaryls, axial chirality in atropisomeric amides maybe introduced by stereochemical control in the atroposelective reactions of planar chiral complexes [115]. Enantioselective lithiation was reported in this context by Uemura, who showed that the achiral complexes 195,198,201 and 204 are de-protonated enantioselectively by treatment with chiral lithium amide bases (Scheme 50) [116-118]. The stereogenic C-C and C-N axes in these compounds are orientated such that the larger NR2 and acyl groups, respectively, are directed away from the chromium. A range of chiral lithium amides was investigated, and by careful selection it was possible to obtain products 196,199,202 and 205... 

The reactions proceeded with high yields (up to 95%) and ee (up to 99%) in the presence of the chiral (7 )-[Mo] catalyst that was efficient in the kinetic resolution of the racemic planar-chiral substrates [17], The stereochemical outcome of the reaction strongly depended on the structure of the allylic group in the phospholyl ligand for R H, R Bu (Scheme 12.11), the bridged product was obtained in 65% yield but with only marginal ee (1%). Fortunately, for R = Me, the a 5a-ferrocenophane was isolated in 72% yield with excellent enantioselectivity (99%). 

Establishment of the absolute configuration of compounds having axial or planar chirality by comparison with a compound containing a chiral centre is a problem of some difficulty. A number of different approaches have been employed many of these entail a form of asymmetric synthesis. A recent review is by G. Krow in Topics stereochem., 1970, 5, 31. In the Atlas it is not possible to portray these various types of asymmetric synthesis in detail, but the user should have no difficulty in consulting the original publications. 

Incorporation of stereogenic centers into cyclic structures produces special stereochemical circumstances. Except in the case of cyclopropane, the lowest-eneigy conformation of the tings is not planar. Most cyclohexane derivatives adopt a chair conformation. For example, the two conformers of cis-l,2-dimethylcyclohexane are both chiral. However, the two conformers are enantiomeric so the conformational change leads to racemization. Because the barrier to this conformational change is low (lOkcal/mol), the two enantiomers arc rapidly interconverted. 

Because an S jl reaction occurs through a carbocation intermediate, its stereochemical outcome is different from that of an S 2 reaction. Carbocations, as we ve seen, are planar, sp2-hybndized, and achiral. Thus, if we carry out an S jl reaction on one enantiomer of a chiral reactant and go through an achiral carbocation intermediate, the product must be optically inactive (Section 9.10). The symmetrical intermediate carbocation can react with a nucleophile equally well from either side, leading to a racemic, 50 50 mixture of enantiomers (Figure 11.10). 

As described above, the stereochemical course of the reaction was proven to be accompanied by inversion of configuration. The most probable explanation is that the substrate adopts a planar conformation at some stage of the reaction, and the chirality of the product is determined by the face of this intermediate that is approached by a proton. If this assumption is correct and the conformation of the substrate in the active site of the enzyme is restricted in some way, the steric bulk of the o-substituents will have some effect on the reactivity. Thus, studies of the o-substituted compounds will give us information on the stereochemistry of the intermediates. 

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