Noyori reaction

Scheme 2.6 Late generation synthesis of desoxy epothilone B and epothilone B. The key steps in this total synthesis are a stereospecific aldol reaction, B-alkyl Suzuki coupling, and stereoselective Noyori reaction.

The conformational distinction between homo- and heterochiral dimers indicates why a bulky dialkylzinc may be important in limiting the scope of amplifying auto catalysis the Soai prescription remains unique. Since it is the product of reaction that is also the catalyst, a further question needs to be addressed. In the conventional Oguni-Noyori reaction discussed earlier [60-71] the zinc alkoxide product normally plays no further part in the proceedings because it forms a stable cubic tetramer [81-87]. There are scattered exceptions in zinc-mediated catalysis, arising when the product structure is conducive to its further involvement [88,89]. 

Reaction of crotylsilanes with aryl acetals Panek and Yang1 have extended the Noyori reaction of allylsiianes with acetals catalyzed by trimcthylsilyl triflate (10,439-440) to optically active (E)-crotylsilanes, such as ar-methoxy-/ -(dimcthylphcnyl-silyl)-(E)-hexenoatcs (1). These (K)-crotylsilanes are available by lreland-Claisen ester rearrangement (6,276-277) of optically active vinylsilancs (equation 1 and 11). 

Formally the process is comparable to an electrochemical reduction on mercury drops (p. 290), but lower yields (30-75%) are obtained sonochemically than electro-chemically (>90%). With unsymmetrical dibromoketones, mixtures of two isomeric a-acetoxy ketones are obtained, but the selectivity is enhanced by using bulkier acids, e.g., trimethyl- or triethyl acetic acid. Oxyallyl cations from a,a -dibromoketones add to olefins or dienes in a [3 + 2] or [3 + 4] mode, the Noyori or Hoffmann-Noyori reaction. 21,322... 

Asymmetric hydrogenation has been achieved with dissolved Wilkinson type catalysts (A. J. Birch, 1976 D. Valentine, Jr., 1978 H.B. Kagan, 1978). The (R)- and (S)-[l,l -binaph-thalene]-2,2 -diylblsCdiphenylphosphine] (= binap ) complexes of ruthenium (A. Miyashita, 1980) and rhodium (A. Miyashita, 1984 R. Noyori, 1987) have been prepared as pure atrop-isomers and used for the stereoselective Noyori hydrogenation of a-(acylamino) acrylic acids and, more significantly, -keto carboxylic esters. In the latter reaction enantiomeric excesses of more than 99% are often achieved (see also M. Nakatsuka, 1990, p. 5586). 

In the last fifteen years macrolides have been the major target molecules for complex stereoselective total syntheses. This choice has been made independently by R.B. Woodward and E.J. Corey in Harvard, and has been followed by many famous fellow Americans, e.g., G. Stork, K.C. Nicolaou, S. Masamune, C.H. Heathcock, and S.L. Schreiber, to name only a few. There is also no other class of compounds which is so suitable for retrosynthetic analysis and for the application of modem synthetic reactions, such as Sharpless epoxidation, Noyori hydrogenation, and stereoselective alkylation and aldol reactions. We have chosen a classical synthesis by E.J. Corey and two recent syntheses by A.R. Chamberlin and S.L. Schreiber as examples. 

A different approach to making chiral drugs is asymmetric synthesis. An optically inactive precursor is converted to the drug by a reaction that uses a special catalyst, usually an enzyme (Chapter 11). If all goes well, the product is a single enantiomer with the desired physiological effect In 2001, William S. Knowles, Ryogi Noyori, and K. Barry Sharpless won the Nobel Prize in chemistry for work in this area. 

The catalytic asymmetric cyclopropanation of an alkene, a reaction which was studied as early as 1966 by Nozaki and Noyori,63 is used in a commercial synthesis of ethyl (+)-(lS)-2,2-dimethylcyclo-propanecarboxylate (18) by the Sumitomo Chemical Company (see Scheme 5).64 In Aratani s Sumitomo Process, ethyl diazoacetate is decomposed in the presence of isobutene (16) and a catalytic amount of the dimeric chiral copper complex 17. Compound 18, produced in 92 % ee, is a key intermediate in Merck s commercial synthesis of cilastatin (19). The latter compound is a reversible... 

The epoxidation method developed by Noyori was subsequently applied to the direct formation of dicarboxylic acids from olefins [55], Cyclohexene was oxidized to adipic acid in 93% yield with the tungstate/ammonium bisulfate system and 4 equivalents of hydrogen peroxide. The selectivity problem associated with the Noyori method was circumvented to a certain degree by the improvements introduced by Jacobs and coworkers [56]. Additional amounts of (aminomethyl)phos-phonic acid and Na2W04 were introduced into the standard catalytic mixture, and the pH of the reaction media was adjusted to 4.2-5 with aqueous NaOH. These changes allowed for the formation of epoxides from ot-pinene, 1 -phenyl- 1-cyclohex-ene, and indene, with high levels of conversion and good selectivity (Scheme 6.3). 

The mechanism of metal-catalyzed /zomo-Diels-Alder reaction proposed by Noyori [57c, 58] requires the coordination of double bonds of diene and... 

For a monograph that discusses most of the reactions in this section, see Stowell, J.C. Carbanions in Organic Synthesis Wiley NY, 1979. For a review, see Noyori, R. in Alper Transition Metal Organometallics, in Organic Synthesis, vol. 1 Academic Press NY,... 

For further applications of this Noyori ketalization compare, e.g. Refs. [6-15]. Interesting also are the reactions of silylated 1,3-diols and 1,3,5-triols with l-... 

Noyori and coworkers found that tetrafluorosilane or trimethylsilyl tri-flate catalyzes the condensation of appropriately protected glycopyranosyl fluorides with trimethylsilyl ethers or alcohols. The strong affinity of silicon for fluorine was considered to be the driving force for this reaction. In the case of Sip4, attack of a nucleophile on the glycosyl cation-SiFj ion-pair intermediate was anticipated. Thus, condensation of 2,3,4,6-tetra-O-benzyl-a- and - -D-glucopyranosyl fluorides (47a and 47fi) with methyl... 

Redox-type reactions show by far the worst performance in meeting the golden atom economical threshold. Three reductions meet this criterion with (AE)min values of 1 hydrogenation of olefins using the Lindlar catalyst (1952), Noyori stereoselective hydrogenation reaction (1985), and Zincke disulphide cleavage reaction (1911) whereas, oxidations... 

As another successful application of Noyori s TsDPEN ligand, Yan et al. reported the synthesis of antidepressant duloxetine, in 2008. Thus, the key step of this synthesis was the asymmetric transfer hydrogenation of 3-(dime-thylamino)-l-(thiophen-2-yl)propan-l-one performed in the presence of (5,5)-TsDPEN Ru(II) complex and a HCO2H TEA mixture as the hydrogen donor. The reaction afforded the corresponding chiral alcohol in both high yield and enantioselectivity, which was further converted in two steps into expected (5)-duloxetine, as shown in Scheme 9.17. 

In order to improve the performance of Noyori s catalytic system, Ru(II)-TsDPEN, which is very efficient but suffers from a long reaction time and a low activity in some cases, Mohar et al. have modified the diamine ligand by... 

TaniaPhos active catalyst discussion As shown by Salzer (2) such complexes with half sandwich stracture result in the catalyst cycle into a hydride species where the pentadienyl moiety can be hydrogenolyticaUy liberated (2, 6). This was verified in the case of BINAP complexes (2, diss. Podewils, Geyser). In accordance to this fact and other mechanistic aspects from Noyori s work (3, 5) it is likely that the pre-catalyst species undergoes the same reaction pathway and that the reactive part of the pre-catalyst, the pentadienyl moiety, will be liberated under hydrogenolytic conditions as shown below in Scheme 23.9 ... 

Kitamura and Noyori have reported mechanistic studies on the highly diastere-omeric dialkylzinc addition to aryl aldehydes in the presence of (-)-i-exo-(dimethylamino)isoborneol (DAIB) [33]. They stated that DAIB (a chiral (i-amino alcohol) formed a dimeric complex 57 with dialkylzinc. The dimeric complex is not reactive toward aldehydes but a monomeric complex 58, which exists through equilibrium with the dimer 57, reacts with aldehydes via bimetallic complex 59. The initially formed adduct 60 is transformed into tetramer 61 by reaction with either dialkylzinc or aldehydes and regenerates active intermediates. The high enantiomeric excess is attributed to the facial selectivity achieved by clear steric differentiation of complex 59, as shown in Scheme 1.22. 

Nonlinearity was also found for this asymmetric organozinc addition, for example, using 50% ee of chiral modifier 46 resulted in 80% ee of adduct 53. The enanti-oselectivity is also dependent on the reaction concentration >98% ee was obtained at 0.1-0.5 M but only 74% ee at 0.005 M. Kitamura and Noyori s work strongly suggested that heterodimer 72 might be more thermally stable than the homodimer... 

Noyori and co-workers have developed a new and useful general synthesis of the tropane alkaloids (89-91). The Fe2(CO)9-aided reaction of tetra-bromoacetone and Af-carbomethoxypyrrole (165) (3 3 1 ratio) in benzene at... 

The most important progress in the last decade has been in the design and synthesis of [RuCl2(diphosphine)(l,2-diamine)] catalysts exploiting the metal-ligand bifunctional concept developed by Noyori and co-workers.29-31 The Noyori catalysts seem to possess all of the desired properties, such as high turnover number (TON), high turnover frequency (TOF), and operationally simple, safe, and environmentally friendly reaction conditions. 

Asymmetric catalysis is four-dimensional chemistry as stated by Noyori,6 because high efficiency can only be achieved through the coordination of both an ideal three-dimensional structure x, y, z) and suitable kinetics (/). Recently developed metal-ligand difunctional catalysts really provide a new basis for developing efficient catalytic reactions. 

A monohydride mechanism is not operating in reactions catalyzed by these complexes. Noyori observed that the presence of an NH or NH2 in the auxiliary ligands was crucial for catalytic activity, the corresponding dialkylamino analogs being totally ineffective. These findings indicate a novel metal-ligand bifunctional cycle (Scheme 28) KOH reacts with the pre-catalyst (87)... 

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