PyBox Lewis acids

In an extension of the PyBox Lewis acids, Loh and co-workers have developed and In(III) based system (88) which is comparable to Keck s original Ti catalyst system in yields and enantioselectivities. To ease in recycling the chiral pybox ligand, Loh has also investigated running the reaction in the presence of ionic liquids to aid in the recovery of the ligand. ... 

In 2010, Loh s group reported a highly efficient catalytic enantioselective polyene cyclization [52]. An a-ketoester was demonstrated to initiate enantioselective cationic polyene cyclization catalyzed by a Sc(OTf)3-Pybox Lewis acid catalyst (Scheme 9.39). 

Ghosh et al. [70] reviewed a few years ago the utihty of C2-symmetric chiral bis(oxazoline)-metal complexes for catalytic asymmetric synthesis, and they reserved an important place for Diels-Alder and related transformations. Bis(oxazoline) copper(II)triflate derivatives have been indeed described by Evans et al. as effective catalysts for the asymmetric Diels-Alder reaction [71]. The bis(oxazoline) Ugand 54 allowed the Diels-Alder transformation of two-point binding N-acylimide dienophiles with good yields, good diastereos-electivities (in favor of the endo diastereoisomer) and excellent ee values (up to 99%) [72]. These substrates represent the standard test for new catalysts development. To widen the use of Lewis acidic chiral Cu(ll) complexes, Evans et al. prepared and tested bis(oxazoHnyl)pyridine (PyBOx, structure 55, Scheme 26) as ligand [73]. 

An alternative approach in the asymmetric catalysis in 1,3-dipole cycloaddition has been developed by Suga and coworkers. The achiral 1,3-dipole 106 was generated by intramolecular reaction of an Rh(ii) carbene complex with an ester carbonyl oxygen in the Rh2(OAc)4-catalyzed diazo decomposition of <9-methoxycarbonyl-o -diazoacetophenone 105 (Scheme 12). The asymmetric induction in the subsequent cycloaddition to G=G and G=N bond was achieved by chiral Lewis acid Sc(iii)-Pybox-/-Pr or Yb(iii)-Pybox-Ph, which can activate the dipolarophile through complexation. With this approach, up to 95% ee for G=0 bond addition and 96% ee for G=G bond addition have been obtained, respectively. ... 

Yu and co-workers32 have reported bis-THF syntheses using Lewis acid-catalyzed reaction of commercially available 2,3-dihydrofiiran (12) and glycolaldehyde dimer 25, as shown in Scheme 5. The use of Sc(OTt)3 and (S)-26 as chiral ligand in CH2C12 at 0 °C provided bis-THF alcohol 11 in a 85 15 mixture of enantiomers by GC analysis. The use of Cu[Pybox] gave similar results. 

Jorgensen et al. reported that C2-symmetric bis(oxazoline)-copper(II) complex 25 also acts as chiral Lewis acid catalyst for a reaction of allylic stannane with ethyl glyoxylate [37]. Meanwhile, p-Tol-BINAP-CuCl complex 26 was shown to be a promising chiral catalyst for a catalytic enantioselective allylation of ketones with allyltrimethoxysilane under the influence of the TBAT catalyst [38]. Evans and coworkers have developed (S,S)-Ph-pybox-Sc(OTf)3 complex 27 as a new chiral Lewis acid catalyst and shown that this scandium catalyst promotes enantioselective addition reactions of allenyltrimethylsilanes to ethyl glyoxylate [39]. But, when the silicon substituents become bulkier, nonracemic dihydrofurans are predominantly obtained as products of [3+2] cycloaddition. 

Other chiral zinc based Lewis acid, such as zinc(II) complex with pybox, showed good stability in aqueous media and gave syn-adducts in moderate to excellent catalytic activity and enantioselectivity for asymmetric Mukaiyama aldol reactions (113,114). A simple combination of Lewis acidic zinc salt (Zn(OTf)2) and organocatalyst is also shown to be effective catalysts for the direct aldol reaction of acetone and aldehydes in the presence of water (115). 

A chiral Sc-pybox catalyst catalyzes Lewis acid-catalyzed enantioselective alkenylation of air- and moisture-stable trimethylvinylsilanes under nuld conditions. Most products are highly crystalline sohds, which are ideally suited for industrial process chemistry (Scheme 4). 

Despite remarkable progress in catalytic asymmetric Diels-Alder reactions using various chiral Lewis acid catalysts [51], only a limited number of chiral catalysts effectively mediate quinone Diels-Alder reactions with moderate to good enantioselectivity [56]. Evans et al. reported that Sm(OTf)3- and Gd(OTf)3-PyBOX... 

The use of chiral copper Lewis acids in enantioselective aldol processes has seen rapid development over the past 10 years. In particular, copper-catalyzed variants of the Mukaiyama aldol reaction received considerable attention in the years leading up to the new millennium. Evans and coworkers first demonstrated Cu(II)/pybox complex (59) as an efficient catalyst for highly enantioselective addition of a variety of silylketene acetals to aldehydes capable ofbidentate coordination (Scheme 17.12) [17]. In reactions utilizing silylketene acetals (61) and (63) with an additional stereoelement, diastereoselectivities and enantioselectivities were also high. A square pyramidal model (65), which has been further supported by a crystal structure of the complex, with the a-alkoxy aldehyde bound in a bidentate fashion accounts for the observed selectivity. 

Li and Li have reported Cu(I)-catalyzed enantioselective alkynylation of prochiral sp C-H bonds adjacent to a nitrogen atom [58]. In this approach, a combination of CuOTf and pybox (197) in the presence of t-BuOOH results in coupling of N-aryl tetrahydroisoquinolines (209) with terminal alkynes (Scheme 17.42). The desired coupling products (211) were generally isolated in moderate to good yields with moderate enantioselectivities. Although it is not clear if the catalytically active Cu(I) species acts as a Lewis acid in this protocol, the chemistry is, nonetheless, worthy of mention. 

The combination of titanium tetraisopropoxide and the TADDOL ligand (Lj in Scheme 11.7) in stoichiometric amount gave products 19 in moderate results (12-46% yields, 32-42% ee) [23]. Significantly better results (75-98% yield, 62-98% ee) were achieved by using tridentate indan(pybox) Cu(II) Lewis acid complex (L2 in Scheme 11.7) as catalyst. The use of carbonyl substrates capable of bidentate coordination was compulsory to give the a-addition to the isocyanide counterpart [24],... 

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