Absolute diols

The first practical method for asymmetric epoxidation of primary and secondary allylic alcohols was developed by K.B. Sharpless in 1980 (T. Katsuki, 1980 K.B. Sharpless, 1983 A, B, 1986 see also D. Hoppe, 1982). Tartaric esters, e.g., DET and DIPT" ( = diethyl and diisopropyl ( + )- or (— )-tartrates), are applied as chiral auxiliaries, titanium tetrakis(2-pro-panolate) as a catalyst and tert-butyl hydroperoxide (= TBHP, Bu OOH) as the oxidant. If the reaction mixture is kept absolutely dry, catalytic amounts of the dialkyl tartrate-titanium(IV) complex are suflicient, which largely facilitates work-up procedures (Y. Gao, 1987). Depending on the tartrate enantiomer used, either one of the 2,3-epoxy alcohols may be obtained with high enantioselectivity. The titanium probably binds to the diol grouping of one tartrate molecule and to the hydroxy groups of the bulky hydroperoxide and of the allylic alcohol... 

Although the first all-sulfur macrocycles were prepared many years ago " the first systematic study of such compounds was initiated by Busch and his coworkers , who were interested in the cation binding properties of such ligands. A sequential synthesis was utilized to produce 1,4,8,11-tetrathiacyclotetradecane [tetrathia-14-crown-4 (70)] . In the first step, 1,3-propanedithiol is metallated using sodium and alkylated with 2-chloroethanol. The diol was then treated with thiourea to form the dimercapto-dithioether compound 9. The latter was once again metallated with sodium and allowed to react with 1,3-dibromopropane. The yield of 70 in the ring closure step, conducted at high dilution in absolute ethanol, was 7.5% after recrystallization. The entire sequence is illustrated in Eq. (6.8) . ... 

Reduction of 17a-EthynyI to 17a-Ethyl °° A solution of 5 g of 17a-ethynyl-androst-5-ene-3j9,17j5-diol in 170 ml of absolute alcohol is hydrogenated at atmospheric pressure and room temperature using 0.5 g of 5 % palladium-on-charcoal catalyst. Hydrogen absorption is complete in about 8 min with the absorption of 2 moles. After removal of the catalyst by filtration, the solvent is evaporated under reduced pressure and the residue is crystallized from ethyl acetate. Three crops of 17a-ethylandrost-5-ene-3) ,17j9-diol are obtained 3.05 g, mp 197-200° 1.59 g, mp 198.6-200.6° and 0.34 g, mp 196-199° (total yield 5.02 g, 90%). A sample prepared for analysis by recrystallization from ethyl acetate melts at 200.6-202.4° [aj, —70° (diox.). 

The synthesis of the key intermediate aldehyde 68 is outlined in Schemes 19-21. The two hydroxyls of butyne-l,4-diol (74, Scheme 19), a cheap intermediate in the industrial synthesis of THF, can be protected as 4-methoxybenzyl (PMB) ethers in 94% yield. The triple bond is then m-hydrostannylated with tri-n-butyl-tin hydride and a catalytic amount of Pd(PPh3)2Cl238 to give the vinylstannane 76 in 98 % yield. Note that the stereospecific nature of the m-hydrostannylation absolutely guarantees the correct relative stereochemistry of C-3 and C-4 in the natural product. The other partner for the Stille coupling, vinyl iodide 78, is prepared by... 

Following Uskokovic s seminal quinine synthesis [40], Jacobsen has very recently reported the first catalytic asymmetric synthesis of quinine and quinidine. The stereospecific construction of the bicyclic framework, introducing the relative and absolute stereochemistry at the Cg- and expositions, was achieved by way of the enantiomerically enriched trans epoxide 87, prepared from olefin 86 by SAD (AD-mix (3) and subsequent one-pot cyclization of the corresponding diol [2b], The key intramolecular SN2 reaction between the Ni- and the Cg-positions was accomplished by removal of the benzyl carbamate with Et2AlCl/thioanisole and subsequent thermal cyclization to give the desired quinudidine skeleton (Scheme 8.22) [41],... 

In order to prove the utility of this method and to ascertain the absolute configuration of the products, (S)-alanine has been enantioselectively prepared. The key step is the addition of methyllithium to the AjA -dimethyl hydrazone acetal 4c, derived from diol 3c. In accordance with 13C-NMR investigations it can therefore be assumed that all major diastereomers resulting from the addition of organolithium reagents to hydrazone acetals 4a-c derived from diols 3a, 3b or 3c (Table 3, entries 1 -6) have an S configuration at the newly formed stereogenic center. 

Madindoline A (7) and B (ent-8) are potent inhibitors of interleukin 6. In a total synthesis [21] that also intended to determine the relative and absolute configurations of these novel antibiotics, the densely functionalized cyclopen-tene-l,3-dione ring of 7 and 8 was elaborated via RCM of diene-diol 2 (Scheme 1). 

Allen CCR, DR Boyd, H Dalton, ND Sharma, I Brannigan, NA Kerley, GN Sheldrake, SC Taylor (1995) Enantioselective bacterial biotransformation routes to cw-diol metabolites of monosubstituted benzenes, naphthalene and benzocycloalkenes of either absolute configuration. J Chem Soc Chem Commun 117-118. 

Akhtar MN, DR Boyd, NJ Thompson, M Koreeda, DT Gibson, V Mahadevan, DM Jerina (1975) Absolute stereochemistry of the dihydroanthracene-ci - and -fra 5,l,2-diols from anthracene by mammals and bacteria. J Chem Soc Perkin I 2506-2511. 

NMR can be a powerful tool for determination of enantiomeric excess or absolute configuration of the optically active compounds, however, these processes require the use of some auxiliaries, for example, chiral lanthanide shift reagents or chiral derivatising agent. In many cases, the starting point for determination of enantiopurity of amines, amino acids or diols is the formation of chiral imines. 

A practical method for the synthesis, resolution and determination of the absolute configuration of 9,9 -binaphtha(2,l- >)furanyl-8,8 -diol was reported as shown below <06TS1275>. A rearrangement of 4-acetoxy-9-furanylnaphtho[2,3- >]furans to tetracyclic naphthodifurans was achieved under acidic conditions <06TL4117>. 

A 2 1 (- )-90-LAH reagent was employed in the asymmetric synthesis of a cij-diol (91) by reduction of c/j-2-acetoxy-6-phenylcyclohexanone (99,100). Diol 91 is of interest as the tetrahydro derivative of a metabolite obtained from the microbial oxidation of biphenyl. Diol 91 was obtained in 46% e.e. as determined by NMR in the presence of a chiral shift reagent. It was shown to have the absolute stereochemistry (lS,2/ )-dihydroxy-3(S)-phenylcyclohexane by oxidation to ( + )-2-(S)-phenyladipic acid of known absolute stereochemistry. 

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