Kagan procedure

Hogan, P. J., Hopes, P. A., Moss, W. O., Rohinson, G. E. and Patel, I. Asymmetric Sulfoxidation of an Aryl Ethyl Sulfide Modification of Kagan Procedure to Provide a Viable Manufacturing Process. Org. Process Res. Dev. 2002, 6, 225-229. 

Hogan PJ, Hopes PA, Moss WO, Robinson GE, Patel 1. Asymmetric sulfoxidation of an aryl ethyl sulfide modification of Kagan procedure to provide a viable manufacturing process. Org. Process Res. Dev. 2002 6 225-229. 

A very interesting approach to optically active sulphoxides, based on a kinetic resolution in a Pummerer-type reaction with optically active a-phenylbutyric acid chloride 269 in the presence of A,N-dimethylaniline, was reported by luge and Kagan (equation 149). In contrast to the asymmetric reductions discussed above, this procedure afforded the recovered sulphoxides in optical yields up to 70%. Chiral a, -unsaturated sulphoxides 270 were prepared via a kinetic resolution elaborated by Marchese and coworkers. They found that elimination of HX from racemic -halogenosulphoxides 271 in the presence of chiral tertiary amines takes place in an asymmetric way leading to both sulphoxides 270 and 271, which are optically active (optical yields up to 20%) with opposite configurations at sulphur (equation 150). 

The nontrivial synthetic procedures to give the tertiary phosphines chiral at phosphorus (10) led Morrison s group (221, 222) to synthesize neomenthyldiphenylphosphine [(+)-NMDPP] (12) and led Kagan s group (10. 223, 224) to synthesize 2,3-o-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane [(-)-DIOP] (13) from the commercially... 

Of several procedures for the stereoselective oxidation of sulfides using organometallic complexes, two adaptations of Kagan s original process have gained prominence. In the first method the diol (36) is reacted with Ti(0 Pr)4 to form the catalyst. With cumyl hydroperoxide as the stoichiometric oxidant, methyl para-tolyl sulfide was converted into the optically active sulfoxide in 42 % yield (98 % ee)[109]. 

The use of furylhydroperoxides[1] has facilitated an operationally simple procedure, alternative to the one reported by Kagan[2]. Oxidation takes place rapidly and very high e.e.s have been obtained, especially in the case of aryl methyl sulfides, while overoxidation to sulfone can be reduced to a great extent (<3 %) under the proposed experimental conditions. 

The experimental procedure is exemplified here with the synthesis of a-6T in = 6) from o -4T (n = 4) (Kagan Arora, 1983). The reaction of two equivalents of q -2T n = 2) with one equivalent of LDA and then with one equivalent of CuCL yields o -4T in high yields. a-2T is obtained from thiophene in a similar way. Then, the reaction of two equivalents of o -4T with one equivalent of LDA followed by one equivalent of CuCF produces o -6T (n = 6). Stoichiometry is thus important. In more detail, a-6T is prepared in the following way. n-BuLi is added... 

Representative procedure - preparation of Sml2 using Kagan s procedure. Samarium powder (3.00 g, 0.02mol) was placed in a reaction flask under an inert atmosphere and a thoroughly degassed solution of 1,2-diiodoethane (2.82 g, 0.01 mol) in dry THF (250 ml) was slowly added. The mixture was stirred at room temperature until a dark blue Sml2 solution was obtained. 

Only a small minority of organometallic reactions have cleared the hurdle to become catalytic reality in other words, catalyst reactivation under process conditions is a relatively rare case. As a matter of fact, the famous Wacker/Hoechst ethylene oxidation achieved verification as an industrial process only because the problem of palladium reactivation, Pd° Pd", could be solved (cf. Section 2.4.1). Academic research has payed relatively little attention to this pivotal aspect of catalysis. However, a number of useful metal-mediated reactions wind up in thermodynamically stable bonding situations which are difficult to reactivate. Examples are the early transition metals when they extrude oxygen from ketones to form C-C-coupled products and stable metal oxides cf. the McMurry (Ti) and the Kagan (Sm) coupling reactions. Only co-reactants of similar oxophilicity (and price ) are suitable to establish catalytic cycles (cf. Section 3.2.12). In difficult cases, electrochemical procedures should receive more attention because expensive chemicals could thus be avoided. Without going into details here, it is the basic, often inorganic, chemistry of a catalytic metal, its redox and coordination chemistry, that warrant detailed study to help achieve catalytic versions. 

A greater percentage of asymmetric induction has been achieved by procedures that generate a reactive coihplex where the sulfide and the oxidant are tightly bound. Kagan and Dunach,578 as well as DiFuria et al., used titanium tetraisopropoxide [Ti(OiPr)4] and optically active diethyl tartrate (DET) to catalyze the... 

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