C2-Symmetric Semicorrins

Inspired by the structures of corrinoid and porphinoid metal complexes, which in nature play a fundamental role as biocatalysts, we have developed a route to chiral C2-symmetric semicorrins 1, a class of bidentate nitrogen ligands specifically designed for enantioselective catalysis [7]. These ligands possess a number of structural features that make them attractive ligands for the stereocontrol of metal-catalyzed reactions. 

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Chiral C2-symmetric semicorrins (structure 4), developed by Pfaltz [11], were proven to be highly efficient ligands for the copper-catalyzed enantio-selective cyclopropanation of olefins. Variations of the substituents at the stereogenic centers led to optimized structures and very high enantioselectiv-ities [12]. 

A remarkable complex (33) with a C2-symmetric semicorrin ligand has been recently developed by Pfaltz and coworkers.64 A copper(II) complex was used as a procatalyst, but (33) was shown to be the active cyclopropanation catalyst. As shown in Table 3, this complex resulted in spectacular enantioselecti-vities in the range of 92-97% ee. Once again, the (15,35,4/ )-menthyl group attenuated the selectivity. Unfortunately, even though respectable yields were obtained with dienes and styrenes, the reaction with 1-heptene was rather inefficient. 

Metal Carbene TVansformations. The effectiveness of Rh2(55 -MEPY)4 and its 5R-form, Rh2 5R-MEPY)4, is exceptional for highly enantioselective intramolecular cyclopropanation and carbon-hydrogen insertion reactions. Intermolecular cyclopropanation occurs with lower enantiomeric excesses than with alternative chiral copper salicylaldimine or C2-symmetric semicorrin or bis-oxazoline copper catalysts, but intermolecular cyclopropenation exhibits higher enantio-control with Rh2(MEPY)4 catalysts. The methyl carboxylate attachment of Rh2(55-MEPY)4 is far more effective than steri-cally similar benzyl or isopropyl attachments for enantioselective metal carbene transformations. The significant enhancement in enantiocontrol is believed to be due to carboxylate carbonyl stabilization of the intermediate metal carbene and/or to dipolar influences on substrate approach to the carbene center. 

Semicorrins have been previously prepared as intermediates in the synthesis of corrinoid and hydroporphinoid compounds [12,13]. The classic route by iminoester-enamine condensation, devisal by Eschenmoser [12], is ideally suited for preparing chiral C2-symmetric semicorrins 1 (Scheme 1). Starting either from L-pyroglutamic acid (-)-3 or from the D-enantiomer, which are both commercially available at moderate prices, the crystalline, enantiomerically pure (S,Sy and (/ ,/ )-diesters (-)-la and (+)-la are readily synthesized in multigram quantities with an overall yield of 30-40 % (Scheme 2) [8,14]. The diesters can be converted to a variety of differently substituted semicorrins by selective trans-... 

In 1986, Pfaltz et al. introduced a new type of pseudo C2-symmetrical copper-semicorrin complex (68) as the catalyst (Scheme 60).227 228 The complexes (68) are reduced in situ by the diazo compound or by pretreatment with phenylhydrazine to give monomeric Cu1 species (69), which catalyze cyclopropanation. Of the semicorrin complexes, complex (68a) (R = CMe2OH) showed the best enantioselectivity in the cyclopropanation of terminal and 1,2-disubstituted olefins.227,228,17 It is noteworthy that complex (68a) catalyzes cyclopropanation, using diazomethane as a carbene source, with good enantioselectivity (70-75% ee).17... 

C2-Symmetric Ligands Chiral Semicorrin/Bis-oxazoline Cu Catalysts... 

Cu complexes with bis-oxazoline ligands 6 that were first reported by Masamune and co-workers [39] have incited considerable interest because of the exceptional enantiocontrol that can be achieved with their use as catalysts for cyclopropanation reactions. Concurrent investigations by Evans [40], who added 7 Masamune, who provided 8 and 9 [41] and Pfaltz [42], who investigated a similar series, established that the C2-symmetric bis-oxazoline ligands are suitable alternatives to semicorrin ligands for Cu in creating a highly enantioselective environment for intermolecular cyclopropanation. For the first time, diazoacetates with ester substituents as small as ethyl could be used to achieve enantioselectivity >90% ee in reactions with styrene (Table 5.4). 

C2-Symmetric Bisoxazolines as Ligands in Asymmetric Catalysis. Methylenebis(oxazolines) such as (1), (3), and (5) are patterned after the semicorrins, which have been successfully employed as ligands in enantioselective Cu-catalyzed cy-clopropanations and other reactions (see (IS,9S)-I,9-Bis [(t-butyl)dimethylsilyloxy]methyl- 5-cyanosemico rrin). The potential of bisoxazoline ligands of this type, which has been recog-... 

In close structural analogy to the semicorrinate ligands of 9, the bidendate, chiral C2-symmetric 5-azasemicorrins 10 and bis(4,5-dihydrooxazol-2-yl)methane systems n is6,2i7 12 218,219 12 a, and 14 perform exceptionally well in copper-catalyzed enantioselective cyclo-... 

In close structural analogy to the semicorrinate ligands of 9, the bidendate, chiral C2-symmetric 5-azasemicorrins 10216 and bis(4,5-dihydrooxazol-2-yl)methane systems li,196 217 12,218 219 12a,197 13,220 and I4197a perform exceptionally well in copper-catalyzed enantioselective cyclo-propanation reactions with diazo esters. With 10, 11, and 12 a, the active catalyst is prepared in situ by adding a catalytic amount of a copper(I) salt with a weakly coordinating anion [copper(I) triflate,196,217,219 copper(I) perchlorate197] to the free ligand with the enolizable system 12 (as well as with 12a and 14) it has been prepared by reaction with copper(I) terh butoxide or from the copper(I) bischelate complex by reduction with phenylhydrazine. 

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