Diol formation

The combination of Eqs. (13-16) implies that both reactions are catalytic under aerobic conditions, which, indeed, they are. The kinetics of catalytic product formation established that two different mechanisms operate. For aldehyde or ketone formation a rate law as in Eq. (18) has been established, whereas the 1,2-diol formation follows the rate law Eq. (19). 

In a variety of cases of epoxide-alkene cyclizations, undesired side reactions such as pinacol rearrangement to carbonyl compounds, or 1,2-diol formation can occur, precluding the cyclization. Corey and Sodeoka have recommended the use of methylaluminum dichloride (MeAlCl2) as catalyst to alleviate such problems <91TL7005>. Equation (3) illustrates the efficacy of this method in effecting optimal yields of cyclization products. 

The total synthesis of the important Hsp90 inhibitor geldanamycin has been described. Two new aldol reactions, as general solutions to anti and syn 1,2 diol formation, were developed for this route. More efficient, convergent approaches, as alternatives to the linear route, were designed... 

Diol formation by reaction of alkenes with osmium tetroxide (sec. 3.5.B). 

Scheme 8.38 Reaction pathway of cis-cyclopropane-1,2-diol formation.

Once formed, 7 and 8 undergo a Michael reaction that gives rise to ketoenamine 9. Ring closure, to form 10, and loss of water then afforded 1,4-dihydropyridine 11. The presence of 9 and 10 could not be detected thus ring closure and dehydration were deduced to proceed faster than the Michael addition. This has the result of making the Michael addition the rate-determining step in this sequence. Conversely, if the reaction is run in the presence of a small amount of diethylamine, compounds related to 10 could be isolated. Diol 20 has been isolated in an unique case (R = CFb). Attempts to dehydrate this compound under a variety of conditions were unsuccessful. Stereoelectronic effects related to the dehydration may be the cause. In related heterocyclic ring formations, it has been determined that dehydration (20 —> 10) is about 10 times slower than diol formation (19 —> 20). Therefore, one would expect 20 to... 

Practical considerations limit, the scalability of this reaction due to the highly reactive and water sensitive intermediates formed. Furthermore, the time required for removal of large amounts of solvent in vacuo allows for the opening of the intermediate epoxide leading to diol formation. 

Lactones can be hydrogenolyzed on copper chromite catalysts.23 Diol formation is favored at lower temperatures, whereas higher temperatures give cyclic ethers. This process is not widely used, however, because of experimental difficulties. 

Endoperoxides of carbocyclic 1,3-dienes are most often transformed into either 1,4-diols, 1,3-diepoxides or 1,4-hydroxyenones. The 1,4-diol formation is illustrated in the synthesis of the sesquiterpene ( )-cybullol (6.8)614). 

In the consecutive hydrogenation of />,<5-diketo esters (Table 21.16), selection of the chiral ligand can determine the sense of diastereoselection, and the 3,5-syn dihydroxy product was formed predominantly upon use of a Ru-(S)-amino-phosphinephosphinite-((S)-AMPP) catalyst, although the enantioselectivity of the syn-product is poor (Table 21.16, entry 7) [103a]. Syn 3,5-diol formation... 

Product of epoxidation of the ring double bond 57%, product of epoxidation of the terminal double bond 4%, 3% diol formation. P 7% of enone. 

Chemoselectivity in the AA process is also dependent on the pH [41] (see above) and the concentration [57] of the reaction mixture. Wuts and coworkers discovered that diol formation increased significantly from 4% to 45% when the concentration was increased from 0.014 to 0.050 g mL-1. Addition of acetamide (1 equivalent) at 0.05 g mL-1 improved the diol/aminoalcohol ratio to 5 95. Interestingly, other amides such as trifluoroacetamide and urea inhibited the reaction while the addition of methanesulfonamide led to large quantities of the diol (70%). 

---