Sharpless ligands

As before, K20s02(0H)4 is in equilibrium with OSO3. TsNCl adds to Os, which uses a lone pair to displace Cl from N and give the key Os(VHE) intermediate. Coordination of the Sharpless ligand creates a complex that adds rapidly to the alkene. Hydrolysis of the Os(VI) product regenerates 0s02(0H)2 and provides the product. 

Recent additional work by Shibata [13b] has shown that related compounds such as oxindoles 20 can also be employed as substrates. Fluorinated oxindole 22 could be obtained with up to 82% ee when the preformed N-F ammonium salt of the Sharpless ligand (DHQD)2PYR (21) was used. 

Although dimeric Sharpless ligands as catalysts showed impressive results in related organocatalytic transformations, they provided only limited success in asymmetric MBH reactions (Scheme 5.12) [70]. These compounds are bifunctional catalysts in the presence of acid additives one of the two amine function of the dimers forms a salt and serves as an effective Bronsted acid, while another tertiary amine of the catalyst acts as a nucleophile. Whereas salts derived from (DHQD)2PYR, or (DHQD)2PHAL afforded trace amounts of products in the addition of methyl acrylate 8a and electron-deficient aromatic aldehydes such as 27, (DHQD)2AQN, 56, mediated the same transformation in ee up to 77%, albeit in low yield. It should be noted that, without acid, the reaction afforded the opposite enantiomer in a slow conversion. 

In 2000, Deng reported that commercially available Sharpless ligands also catalyze the highly enantioselective alcoholysis of meso-cyclic anhydrides [179]. 

Although dimeric Sharpless ligands, as another kind of cinchona catalyst, showed impressive results in related organocatalytic transformations, they provided only limited success in asymmetric MBH reactions (Scheme 2.78). These compounds can act as bifunctional catalysts in the presence of acid... 

The Sharpless ligand (DHQD>2AQN 45 was introduced to the asymmetric BH reaction in combination with acetic acid as co-catalyst. The ammonium salt generated in situ was proposed as a bifunctional catalyst, where the protonated amine acted as Brpnsted acid and the nonprotonated one performed as nucleophilic catalyst [99]. Besides, a simple phosphine-sulfonamide 46, synthesized readily from L-threonine, was found to be an efficient catalyst for the reaction of 7V-sulfonyl imines and (3-naphthyl acrylate to give the product in excellent enantioselectivities [100]. 

By using a chiral Sharpless ligand, high enantioselectivities were obtained. In the flavin system, an increase in the addition time for alkene and H2O2 has a positive... 

It is well known that tertiary ally lie alcohols such as 21 can be oxidized to the corresponding enone 23 with chromium reagents. Yoshiharu Iwabuchi of Tohoku University observed (J. Org. Chem. 2008, 73, 4750) that the oxammonium salt 22 derived from TEMPO effected the same transformation. David E. Richardson of the University of Florida found (Tetrahedron Lett. 2008, 49, 1071) that could be used to oxidize N-methyhnorpholine in situ to the N-oxide, that in turn reoxidized catalytic OsO. In the presence of the Sharpless ligand, the dihydroxylation proceeded withhighee. This approach could offer cost and waste stream advantages over currently used oxidants. 

Sharpless Asymmetric Dihydroxylation (AD) - Ligand pair are really diastereomers ... 

The Sharpless-Katsuki asymmetric epoxidation reaction (most commonly referred by the discovering scientists as the AE reaction) is an efficient and highly selective method for the preparation of a wide variety of chiral epoxy alcohols. The AE reaction is comprised of four key components the substrate allylic alcohol, the titanium isopropoxide precatalyst, the chiral ligand diethyl tartrate, and the terminal oxidant tert-butyl hydroperoxide. The reaction protocol is straightforward and does not require any special handling techniques. The only requirement is that the reacting olefin contains an allylic alcohol. 

In eonjunetion with the addition of moleeular sieves. Sharpless et al. as also developed an in situ derivatization of produet epoxy aleohols that were previously diffieult to isolate. The derivatization of the produet has been aeeomplished via esterifieation or sulfonylation of the aleohol funetionality. The derivatization is possible only under eatalytie eonditions given the overwhelming presenee of isopropoxide from stoiehiometrie amounts of Ti(0-i-Pr)4 and the presenee of the diol ligand diethyl tartrate. 

The AE reaction has been applied to a large number of diverse allylic alcohols. Illustration of the synthetic utility of substrates with a primary alcohol is presented by substitution pattern on the olefin and will follow the format used in previous reviews by Sharpless but with more current examples. Epoxidation of substrates bearing a chiral secondary alcohol is presented in the context of a kinetic resolution or a match versus mismatch with the chiral ligand. Epoxidation of substrates bearing a tertiary alcohol is not presented, as this class of substrate reacts extremely slowly. 

A model for the catalytically active species in the Sharpless epoxidation reaction is formulated as a dimer 3, where two titanium centers are linked by two chiral tartrate bridges. At each titanium center two isopropoxide groups of the original tetraisopropoxytitanium-(IV) have been replaced by the chiral tartrate ligand ... 

Another important reaction associated with the name of Sharpless is the so-called Sharpless dihydroxylation i.e. the asymmetric dihydroxylation of alkenes upon treatment with osmium tetroxide in the presence of a cinchona alkaloid, such as dihydroquinine, dihydroquinidine or derivatives thereof, as the chiral ligand. This reaction is of wide applicability for the enantioselective dihydroxylation of alkenes, since it does not require additional functional groups in the substrate molecule ... 

Figure 2. Structures of phthalazine (32,33), pyrimidine (34,35), and indoline (36,37) ligands used in the Sharpless AD and composition of AD-mix a and AD-mix p.

Ten years after Sharpless s discovery of the asymmetric epoxidation of allylic alcohols, Jacobsen and Katsuki independently reported asymmetric epoxidations of unfunctionalized olefins by use of chiral Mn-salen catalysts such as 9 (Scheme 9.3) [14, 15]. The reaction works best on (Z)-disubstituted alkenes, although several tri-and tetrasubstituted olefins have been successfully epoxidized [16]. The reaction often requires ligand optimization for each substrate for high enantioselectivity to be achieved. 

The epoxidation of allylic alcohols can also be effected by /-butyl hydroperoxide and titanium tetraisopropoxide. When enantiomerically pure tartrate ligands are included, the reaction is highly enantioselective. This reaction is called the Sharpless asymmetric epoxidation.55 Either the (+) or (—) tartrate ester can be used, so either enantiomer of the desired product can be obtained. 

This method has proven to be an extremely useful means of synthesizing enantiomeri-cally enriched compounds. Various improvements in the methods for carrying out the Sharpless oxidation have been developed.56 The reaction can be done with catalytic amounts of titanium isopropoxide and the tartrate ligand.57 This procedure uses molecular sieves to sequester water, which has a deleterious effect on both the rate and enantioselectivity of the reaction. 

Fig. 12.4. Successive models of the transition state for Sharpless epoxidation. (a) the hexacoordinate Ti core with uncoordinated alkene (b) Ti with methylhydroperoxide, allyl alcohol, and ethanediol as ligands (c) monomeric catalytic center incorporating t-butylhydroperoxide as oxidant (d) monomeric catalytic center with formyl groups added (e) dimeric transition state with chiral tartrate model (E = CH = O). Reproduced from J. Am. Chem. Soc., 117, 11327 (1995), by permission of the American Chemical Society. 

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