Noyori hydrogenation

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. 

Preparation of the Aldehyde 2 The absolute configuration of the iriene aldehyde 2 was set by Noyori hydrogenation of ethyl butyrylacetate S. Silylation and Dibal reduction then gave the aldehyde 6. Reduction of the homologated ester gave the alcohol, which was oxidized to the desired aldehyde 7 by the Swem procedure. Condensation of 7 with the Wollenberg stannyl diene followed by deprotection then gave the unstable aldehyde 2. 

Hydrogenation of olefins, enols. or enamines with chiral fVilkinson type catalysts, e.g., Noyori hydrogenation. Hydroboration of olefins with chiral boranes. Sharpless epoxi-dation of allylic alcohols. 

The potential of a catalytic process for use on a large scale can be a good indication of its efficiency. During recent decades there has been an increasing tendency to apply asymmetric catalytic processes in industry [1], The asymmetric Noyori hydrogenation [2] and the Sharpless and Jacobsen-Katsuki epoxidation [3] are representative examples of impressive developments in this field [1]. 

This is mainly due to the fact that by means of chiral ligands it is comparatively facile to transfer absolute stereochemical information to a cat-alytically active metal center. However, the success of some of these reactions (e.g. the Sharpless asymmetric epoxidation or the Noyori hydrogenation) must not hide the fact that the number of powerful transition metal-catalyzed C-C coupling reactions, which proceed reliably with high enantioselectivity, is still rather small. 

Nonanedioic add, 5-hydroxy-2,4,6,8-tetramethyl- diastereoselective lactonization, 168, 327-328 2,4-Nonanedione retro-synthesis, 204 Norbomane etc. See Bicyclo[2.2.1 ] heptane ere. Norphedrine = (/ , S )-a-benzene-methanol, ( + H S)- chiral auxiliary, 61 —, ( ) synthesis, 302 Norgestrel, ( )- total synth., 278 19-Norpregna-1,3,5(10)-trien-2-yne-3,l 7-diol, (17a)- [ethynylestradiofy 62-63 A-Norpregn-3(5)-eri-20-one, 3-methyl- synthesis, 91-92, 279-280 Noyori hydrogenation, 102-103, 325-326 SI Nuclease, 242... 

Other references related to the Noyori hydrogenation are cited in the literature. ... 

The aldehyde 218 possessing 2,6-frans-tetrahydropyran, was synthesized as shown in Scheme 48. /3-Keto ester 220 was reduced by Noyori hydrogenation [97] to give 6-hydroxy ester 221 in 94% ee, which was converted into iodide 222. Asymmetric alkylation using Myers chiral auxiliary [98] with 222, followed by acid treatment, furnished 5-lactone 223 with high stereoselectivity. Reductive acetylation, axial allylation by the Hosomi-Sakurai reaction, and ozonolysis completed the synthesis of 218. 

Faza, O. N. L6pez, C. S. Fernandez, I. Noyori hydrogenation Aromaticity, synchronicity, and activation strain analysis. /. Org. Chem. 2013, 78,5669-5676. 

Scheme 8.43)." The aldol reaction of aldehyde 272 and alkynylketone 273 catalyzed with Zn(ll)-265 complex gave (3-hydroxyketone 274 in excellent stereoselectivity. Noyori hydrogen transfer reaction provided the central diol moiety of fostriecin 278. They accomplished the asymmetric synthesis of 277, therefore, the formal synthesis of fostriecin 278. 

Reiff EA, Nair SK, Reddy BSN, Inagaki J, Henri JT, Greiner JF, Georg GI. Practical syntheses of the C12-C21 epothilone subunit via catalytic asymmetric reductions Itsuno-Corey oxazaborolidine reduction and asymmetric Noyori hydrogenation. Tetrahedron Lett. 2004 45(30) 5845-5847. 

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