Dihydroxylation amine accelerated

Enantioselective Dihydroxylation. The acceleration of osmylation by tertiary amines brought about the use of chiral amines... 

The interest in asymmetric synthesis that began at the end of the 1970s did not ignore the dihydroxylation reaction. The stoichiometric osmylation had always been more reliable than the catalytic version, and it was clear that this should be the appropriate starting point. Criegee had shown that amines, pyridine in particular, accelerated the rate of the stoichiometric dihydroxylation, so it was understandable that the first attempt at nonenzymatic asymmetric dihydroxylation was to utilize a chiral, enantiomerically pure pyridine and determine if this induced asymmetry in the diol. This principle was verified by Sharpless (Scheme 7).20 The pyridine 25, derived from menthol, induced ee s of 3-18% in the dihydroxylation of /rcms-stilbene (23). Nonetheless, the ee s were too low and clearly had to be improved. 

More than sixty years ago, Criegee reported that the dihydroxylation of olefins by osmium tetroxide was accelerated by the addition of a tertiary amine.165 166 Later, this discovery prompted the study of asymmetric dihydroxylation, because the use of an optically active tertiary amine was expected to increase the reaction rate (kc > k0) and to induce asymmetry (Scheme 41).167... 

About a decade after the discovery of the asymmetric epoxidation described in Chapter 14.2, another exciting discovery was reported from the laboratories of Sharpless, namely the asymmetric dihydroxylation of alkenes using osmium tetroxide. Osmium tetroxide in water by itself will slowly convert alkenes into 1,2-diols, but as discovered by Criegee [15] and pointed out by Sharpless, an amine ligand accelerates the reaction (Ligand-Accelerated Catalysis [16]), and if the amine is chiral an enantioselectivity may be brought about. 

Organometallic compounds asymmetric catalysis, 11, 255 chiral auxiliaries, 266 enantioselectivity, 255 see also specific compounds Organozinc chemistry, 260 amino alcohols, 261, 355 chirality amplification, 273 efficiency origins, 273 ligand acceleration, 260 molecular structures, 276 reaction mechanism, 269 transition state models, 264 turnover-limiting step, 271 Orthohydroxylation, naphthol, 230 Osmium, olefin dihydroxylation, 150 Oxametallacycle intermediates, 150, 152 Oxazaborolidines, 134 Oxazoline, 356 Oxidation amines, 155 olefins, 137, 150 reduction, 5 sulfides, 155 Oxidative addition, 5 amine isomerization, 111 hydrogen molecule, 16 Oxidative dimerization, chiral phenols, 287 Oximes, borane reduction, 135 Oxindole alkylation, 338 Oxiranes, enantioselective synthesis, 137, 289, 326, 333, 349, 361 Oxonium polymerization, 332 Oxo process, 162 Oxovanadium complexes, 220 Oxygenation, C—H bonds, 149... 

Thus, in cw-vic-dihydroxylations of alkenes with 0s04 tertiary amines, like pyridine, have ligand acceleration effects (this term was introduced in Section 3.4.6, using the Sharpless epoxidation as an example). 

The most popular method for dihydroxylation of alkenes uses osmium tetroxide. This reagent can be used stoichiometrically, although its expense and toxicity have led to the development of catalytic variants. There has been considerable debate over the mechanism of the reaction, which has been postulated to proceed by a direct [3 4-2] cycloaddition, or via a [2-1-2] cycloaddition followed by a rearrangement, to give the intermediate osmate ester.This osmium(Vl) species can be oxidized or reduced and hydrolysed to release the diol product (5.79). The reaction is accelerated by tertiary amine and other bases, such as pyridine, which co-ordinate to the osmium metal. 

The reaction has been proposed to proceed through a [3 -1- 2] or [2-1-2] pathway to give the common intermediate osmium(VI) monoglycolate ester (osmate ester), which is then hydrolyzed reductively or oxidatively to give the cd-1,2-diol (eq 2). The cis dihydroxylation of alkenes is accelerated by tertiary amines such as Pyridine, quinucUdine, and derivatives of dihydroquini-dine (DHQD) or dihydroquinine (DHQ) (eq 3). 

Now for the chiral ligand. Tertiary amines are good ligands for osmium and increase the rate of dihydroxylations one of the reasons that NMO is used in the racemic version of the reaction q (see p. 442) is that the by-product, N-methylmorpholine, accelerates the reaction. Sharpless p ... 

In the presence of a chiral amine such as quinine, Sharpless has demonstrated asymmetric catalysis for this dihydroxylation reaction that is also accelerated by this type of ligand. The oxidizing agent (oxygen donor) is then amine oxide. This system compares with Jacobsen s efficient hydrolytic kinetic resolution shown in section 4, but extension to the industrial scale is more problematic with the Sharpless system. 

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