Enantioselectivity flexibility

Relationships between stereocenters vary between two extremes. On the one hand, stereocenters may interact strongly in a spatial sense if they are directly joined, proximate to one another, or part of a compact rigid-ring structure. On the other hand, two stereocenters which are remote from one another and/or flexibly connected may be so independent that one cannot be used to provide substrate spatial control for the other. Nonetheless, this latter type of stereorelationship may still be clearable if the target molecule can be disconnected to divide the two stereocenters between two precursors or if an appropriate enantioselective transform is available. 

Significant advance in the field of asymmetric catalysis was also achieved with the preparation of l,2-bis(phospholano)benzene (DuPHOS 4) and its confor-mationally flexible derivative (l,2-bis(phospholano)ethane, known as BPE) by Burk et al. [59]. Two main distinctive features embodied by these Hgands, as compared to other known chiral diphosphine ligands, are the electron-rich character of the phosphorus atoms on the one hand and the pseudo-chirality at phosphorus atoms, on the other. These properties are responsible for both the high activity of the corresponding metal complex and an enantioselection indepen-... 

In the presence of the corresponding copper(II) catalyst, N-acryloyloxazo-lidinone reacted with various conjugated dienes (cyclic and acychc) with good enantioselectivities in all cases, competing with results obtained for classical catalysts in the case of flexible dienes. Thus the cycloadducts obtained from isoprene or 2,3-dimethyl-1,3-butadiene were synthesized in high yields and good enantioselectivities (92% ee in both cases). 

The low-temperature method has been applied to some primary and secondary alcohols (Fig. 1) For example, solketal, 2,2-dimethyl-1,3-dioxolane-4-methanol (3) had been known to show low enantioselectivity in the lipase-catalyzed resolution (lipase AK, Pseudomonas fluorescens, E = 16 at 23°C, 27 at 0oc) 2ia however, the E value was successfully raised up to 55 by lowering the temperature to —40°C (Table 1). Further lowering the temperature rather decreased the E value and the rate was markedly retarded. Interestingly, the loss of the enantioselectivity below —40°C is not caused by the irreversible structural damage of lipase because the lipase once cooled below —40°C could be reused by allowing it to warm higher than -40°C, showing that the lipase does not lose conformational flexibility at such low temperatures. 

Other bis(sulfonamides) ligands based on more flexible diamines have been investigated by Denmark et al. as promoters for the enantioselective Simmons-Smith cyclopropanation of cinnamyl alcohol. This study has revealed a... 

At the turn of the millennium, Zhang and RajanBabu have independently returned to derivatives of DIOP and found that the introduction of a-methyl groups as in DIOP (13) greatly increases enantioselectivity [76-79]. Zhang attributes this improvement to a reduction in the conformational flexibility of the backbone within the metal complex [3, 76]. It is interesting to note that Kagan himself prepared the S,S,S,S-isomer of DIOP, but enantioselectivities were lower than with DIOP itself [80]. 

Until now, only two families of ligands have been realized where both P groups are attached to side chains, probably because the resulting metal complexes have relatively large chelate rings which usually are not suitable for enantioselective catalysis. A cursory inspection of the ligands depicted in Fig. 25.14 shows that, due to steric bulk of the ferrocene backbone, both diphosphines probably have sufficiently restricted flexibility so that good stereocontrol is still possible. 

DM-BIPHEP, a conformationally flexible diphosphine, exists as an equilibrium mixture of the R and S isomers (Fig. 32.50) [141]. Addition of an equimolar amount of (S,S)-DPEN to RuCl2(dm-biphep)(dmf) forms a 3 1 mixture of (S)-DM-BIPHEP/(S,S)-DPEN-RuC12 complex and the R,SS diastereoisomer. The major S,SS complex gives a more active and enantioselective catalyst for the hydro-... 

Yet, indirect information on enantioselective complexation by silica-bound antibiotics in HPLC can be extracted from the analysis of retention data of several ligands whose structure is systematically varied to explore chemical diversity in terms of functional groups, stereogenic elements, molecular complexity, and rigidity-flexibility. 

Other 2, 2 -disubstitued biferrocene derivatives (ligands 2, Fig. 3) also tested using the dinuclear [Ir( r-Cl)(COD)]2 as the iridium source provided total conversion in arylimine hydrogenation, although with poor-to-moderate enantioselectivity (20-33% ee) [17]. The low enantioselectivies are assumed to be related to the conformational flexibility of this type of bifep ligands. 

Shibasaki et al. developed a polymer-supported bifunctional catalyst (33) in which aluminum was complexed to a chiral binaphtyl derivative containing also two Lewis basic phosphine oxide-functionahties. The binaphtyl unit was attached via a non-coordinating alkenyl Hnker to the Janda Jel-polymer, a polystyrene resin containing flexible tetrahydrofuran-derived cross-Hnkers and showing better swelling properties than Merifield resins (Scheme 4.19) [105]. Catalyst (33) was employed in the enantioselective Strecker-type synthesis of imines with TMSCN. 

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