Carbohydroxylation

B2(cat)2 = bis(catecholato)boron Scheme 6.17 Catalytic asymmetric carbohydroxylation of alkenes. 

Carbo-oxylation (carbohydroxylation and carboalkoxylation), whereby an organic group and an oxy (hydroxyl or alkoxy) group add across a carbon-carbon double bond or a triple bond, is an important transformation in organic synthesis. We found that the reaction of a cation pool with an alkene or alkyne followed by the trapping of the resulting carbocation by water led to the... 

Applications. In the last decade a lot of research has been devoted to the development of catalytic routes to a series of asymmetric carboxylic acids that lack the acetamido ligand as additional functionality. In Figure 4.17 four are listed, which are important as anaesthetics for rheumatic diseases. Their sales in beat many bulk chemicals the turnover of Naproxen (retail) in 1990 was 700 million for 1000 tons. S-Naproxen is now being produced by Syntcx via resolution with a chiral auxiliary. The main patents from Syntex expired in the U.S. in 1993, the reason for a lot of activity to study alternative synthetic routes. Routes leading to an asymmetric centre are o asymmetric hydrogenation of an unsaturated acid, o asymmetric carbohydroxylation of a styrene precursor, o asymmetric hydroformylation of a styrene precursor and oxidation. 

In comparison to the other strategies employed for the synthesis of preussin the carbohydroxylation sequence we chose is unique. It has remained the only strategy which does not include the formation of the pyrrolidine... 

S-Naproxen is being produced by Syntex by resolution with a chiral auxiliary. The main patents from Syntex expired in 1993, which represents the main drive for an increase in the efforts to find alternative synthetic routes which may lead directly to an asymmetric carbohydroxylation of the styrene precursor. Asymmetric hydrogenation of molecules of this type has been successfully accomplished by Noyori using ruthenium complexes of the ligand BINAP (Fig. 6.30). With this system a high enantioselectivity can be achieved (97%) albeit at rather high pressures (135 bar). Monsanto [79] claims a similar route that operates at a much lower pressure. The reaction scheme is shown in Fig. 6.31. 

The reaction of an N-acyliminium ion pool with an alkene or alkyne followed by trapping of the resulting carbocation by water leads to the formation of the corresponding carbohydroxylation product. Cationic sequential one-pot, three-component coupling reactions of an N-acyliminium ion can also be accomplished using an electron-rich olefin and a suitable nucleophile that traps the thus-generated cationic intermediate as shown in Scheme 5.17. ... 

I.5.8.4. Additions with C-C/C-Heteroatom Bond Formation (Heterocarboration) 1.5.8.4.1. Carbohydroxylation, Carboalkoxylation and Carbocarboxylation... 

The reactions initiated by the addition of a carbon-carbon multiple bond to the cation pool bring in unique one-pot transformations otherwise difficult to realize, because the reactive carbocations are existing in the solution in relatively high concentration. For example, a sequential one-pot three-component coupling reactions have been developed (Scheme 5) [9, 10]. [4 -f 2] cyclo addition reactions in which an N-acyliminium ion was used as a hetero diene [11], and cationic carbohydroxylation of alkenes and alkynes using the cation pool method [12] were also accomplished. 

Suga S, Kageyama Y, Babu G, Itami K, Yoshida J (2004) Cationic carbohydroxylation of alkenes and alkynes using the cation pool method. Org Lett 6 2709-2711... 

Bach, T., Regioselective carbohydroxylation of enol ethers by a photocycloaddition-hydrogenation sequence. Tetrahedron Lett., 35, 1855, 1994. 

Bach, T, Regioselective ring opening of oxetanes by hydrogenolysis a convenient method for the carbohydroxylation of enol ethers, Liebigs Ann., 1045, 1995. 

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