Asymmetric reduction, ruthenium transformation

Annual Volume 71 contains 30 checked and edited experimental procedures that illustrate important new synthetic methods or describe the preparation of particularly useful chemicals. This compilation begins with procedures exemplifying three important methods for preparing enantiomerically pure substances by asymmetric catalysis. The preparation of (R)-(-)-METHYL 3-HYDROXYBUTANOATE details the convenient preparation of a BINAP-ruthenium catalyst that is broadly useful for the asymmetric reduction of p-ketoesters. Catalysis of the carbonyl ene reaction by a chiral Lewis acid, in this case a binapthol-derived titanium catalyst, is illustrated in the preparation of METHYL (2R)-2-HYDROXY-4-PHENYL-4-PENTENOATE. The enantiomerically pure diamines, (1 R,2R)-(+)- AND (1S,2S)-(-)-1,2-DIPHENYL-1,2-ETHYLENEDIAMINE, are useful for a variety of asymmetric transformations hydrogenations, Michael additions, osmylations, epoxidations, allylations, aldol condensations and Diels-Alder reactions. Promotion of the Diels-Alder reaction with a diaminoalane derived from the (S,S)-diamine is demonstrated in the synthesis of (1S,endo)-3-(BICYCLO[2.2.1]HEPT-5-EN-2-YLCARBONYL)-2-OXAZOLIDINONE. 

Asymmetric reductive acetylation was also applicable to acetoxyphenyl ketones. In this case the substrate itself acts as an acyl donor. For example, m-acetoxyace-tophenone was transformed to (R)-l-(3-hydroxyphenyl)ethyl acetate under 1 atm H2 in 95% yield [16] (Scheme 1.12). The pathway of this reaction is rather complex. It was confirmed that nine catalytic steps are involved two steps for ruthenium-catalyzed reductions, two steps for ruthenium-catalyzed racemizations, two steps... 

Asymmetric catalysis undertook a quantum leap with the discovery of ruthenium and rhodium catalysts based on the atropisomeric bisphosphine, BINAP (3a). These catalysts have displayed remarkable versatility and enantioselectivity in the asymmetric reduction and isomerization of a,P- and y-keto esters functionalized ketones allylic alcohols and amines oc,P-unsaturated carboxylic acids and enamides. Asymmetric transformation with these catalysts has been extensively studied and reviewed.81315 3536 The key feature of BINAP is the rigidity of the ligand during coordination on a transition metal center, which is critical during enantiofacial selection of the substrate by the catalyst. Several industrial processes currently use these technologies, whereas a number of other opportunities show potential for scale up. 

Ruthenium/BINAP complexes have been successfully used in the asymmetric reduction of acrylic acids. This methodology has been used to prepare the antiinflammatory drug (S)-Naproxen (2.78) by reduction of the acrylic acid (2.77). Ruthenium/PQ-Phos species catalyse the same transformation with comparable ee. ... 

In this chapter, I outline our recent progress in asymmetric reductive and oxidative transformations with bifunctional molecular catalysts based on ruthenium, rhodium, and iridium complexes bearing chiral chelating amine ligands. 

Several other mechanistically distinct metal-catalyzed dearomatization procedures have been reported, and almost all involve phenol or naphthol derivatives undergoing dearomatization via intramolecular transformations. Intramolecular Pd- and Rh-catalyzed C4-arylation and alkylation of /)ara-substituted phenols has been used to construct compounds of general structure 82 (Fig. 15.1) [86]. These reactions rely on generation of electrophilic aryl or alkyl o-metal complex intermediates that participate in tandem C4 metalation-reductive elimination with an attached phenol. Ruthenium- and Pt-catalyzed reactions of naphthalenes and alkynes deliver spirocyclic products such as 83 [87, 88]. An asymmetric intramolecular naphthalene dearomatization catalyzed by Pd(0)-phosphine complexes has been used to prepare carbazole derivatives 84 in good enantiomeric excess from l-(AI-2-bromophenyl)aminonaphthalene precursors [89]. 

Kejrwords Dynamic kinetic asymmetric transformation (DYKAT) Dynamic kinetic resolution (DKR) Hydrogenation Imine reduction Ketone reduction Mechanism of carbonyl reduction Mechanism of imine reduction Mechanism of dUiydrogen activation Ruthenium catalysis Shvo s catalyst Transfer hydrogenation... 

While the asymmetric HDA has proven to be an effective mediod for the construction of DHP/THP motifs, additional methods based on a metal-mediated/metal-catalyzed coupling and cycUzatirMi strategy are burgerming. The study of cationic ruthenium in ene-type addition of alkenes to acetylenes has been studied previously [120], and Trost et al. recently reported an alternative approach to HDA THP cycloadducts by a similar process [121], The first step of the transformation involves addition of the Ru-alkene complex of 247 to acetylene 248 followed by reductive elimination to give an enone. The enone subsequently undergoes a conjugate addition with the pendant alcohol to afford the desired 2,6-cfs-tetrahydropyran 249. 

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