Allylic alcohol groups

A catalytic enantio- and diastereoselective dihydroxylation procedure without the assistance of a directing functional group (like the allylic alcohol group in the Sharpless epox-idation) has also been developed by K.B. Sharpless (E.N. Jacobsen, 1988 H.-L. Kwong, 1990 B.M. Kim, 1990 H. Waldmann, 1992). It uses osmium tetroxide as a catalytic oxidant (as little as 20 ppm to date) and two readily available cinchona alkaloid diastereomeis, namely the 4-chlorobenzoate esters or bulky aryl ethers of dihydroquinine and dihydroquinidine (cf. p. 290% as stereosteering reagents (structures of the Os complexes see R.M. Pearlstein, 1990). The transformation lacks the high asymmetric inductions of the Sharpless epoxidation, but it is broadly applicable and insensitive to air and water. Further improvements are to be expected. 

Scheme 11). This kind of catalyst is regioselective, the remote C=C being unaffected, thus indicating that the allylic alcohol group provides a necessary secondary coordination during the cycle. Further confirmation comes from the evidence that extension of the carbon chain by just one more carbon, with respect to homoallylic alcohols, results in no reaction. 

Formation of 173 from 171 on hydrogenation pointed to the presence of an allylic alcohol group in 171. This was confirmed by oxidation of 171 to ketone 174. There were strong bands at 1650 and 1580 cm in the IR spectrum of 174 typical for a —CO—C=C—— system. The absence of olefmic protons in the NMR spectrum of 171 suggested the double bond to be at C-11—C-16, while a hydroxyl group is positioned at C-15 or C-17. 

The oxidant for the epoxidation is re/-/-Butyl hydroperoxide. The reaction is catalyzed by Ti(0/Pr)4, which binds the hydroperoxide, the allylic alcohol group, and the asymmetric tartrate ligand via oxygen atoms (putative transition state depicted below). 

N-Deprotection of benzotriazole derivatives 33 produces a benzyne intermediate that upon interaction with iV-iodosuccinimide (NIS) undergoes intramolecular trapping by the hydroxyl group with concomitant incorporation of iodine to afford 8-iodo-2/7-chromenes (Scheme 10). However, the dimethyl derivative (R1 = Rz = Me), when treated with TFA, undergoes dehydration of the allylic alcohol group rather than N-deprotection <2000J(P1)2343>. 

Asymmetric hydrogenation of allylic alcohols (14, 39-40).1 Mammalian dol-ichols (2) are terminal dihydropolyisoprenols which are involved in glycoprotein synthesis. They contain one terminal chiral primary allylic alcohol group. The polyprenols 3 present in plants correspond to dolichols except that they lack the terminal double bond considered to be (Z). They can be obtained by hydrogenation of 2 catalyzed by (bistrifluoroacetate)ruthenium(II) and (S)-l, which affects only the terminal double bond to provide (S)-3 in >95% ee. 

The allylic alcohol (273) has also been used in a preparation of 15-oxo-15,20S-dihydrocatharanthine (275a), required for partial synthesis of anhydro-vinblastine (q.v.).125 Oxidation of (273) could be achieved by a variety of oxidizing agents, of which triphenylbismuth carbonate appeared to be the best (Scheme 39). Oxidation of the allylic alcohol group was followed by Michael addition of Nb to the... 

A c.d. correlation confirmed that (+ )-5-carotene (20) has the same absolute stereochemistry at C-6 as (-f )-a-carotene (21). Lutein (22) was also shown to have this absolute stereochemistry at C-6 by c.d. correlation with natural zein-oxanthin (23). In order to do this, the allylic alcohol group was removed by Corey s method using the sulphur trioxide-pyridine complex followed by... 

For acyclic allylic alcohols, very little a,p-unsaturated enone formation was observed besides epoxidation. Chemoselectivity was much less for cyclic allylic alcohols, for which oxidation of fhe allylic alcohol group competed significantly with epoxidation. In the case of 2-cyclohexenol as the substrate, the enone was even found to be the main product. A comparative sandwich POM-catalyzed epoxidation study of various (subsfifufed) cycloalkenols revealed that the enone versus epoxide chemoselectivity is controlled by the C=C-C-OH dihedral angle Ma in the allylic alcohol substrate. The more this dihedral angle deviates from fhe optimum C=C-C-OW dihedral angle otw for allylic acohol epoxidation, the more enone is formed (Fig. 16.5). 

Scheme 8.2. (a) Addition of m-CPBA from the face opposite to the allylic acyloxy or trimethylsilyloxy ligand, (b) Proposed delivery of peracid to the P-face of the substrate mediated by the allylic alcohol group. Other modes of hydrogen bonding have been proposed for this type of reagent delivery [4,5]. 

Conformational arguments relative to the structure of ajaconine have shown that A/B-trans stereochemistry is present in atisine (25). Differentiation between isomers L and LI in which a trans-anti backbone is present, involves the choice of locating the allylic alcohol group on the trans (with respect to nitrogen) (isomer L) or cis branch (isomer LI) of the... 

The initial selection of adjuvants to crinitol was based largely on the above mentioned structure-activity relationship study. Thus, the hydroxy group at C-9 in crinitol seems to be essential to its antibacterial activity. The allylic C-9 hydroxy group is easily oxidized, a possibility which might detoxify crinitol in bacterial systems. Because crinitol possesses two allylic alcohol groups in its molecule (at C-1 and C-9), we combined it with several antioxidants which have been used as food and cosmetic additives. Thus two natural antioxidants, vitamins C and E, and two synthetic antioxidants, BHA and BHT, were chosen for the experiment. While the synthetic antioxidants exhibited antimicrobial activity against all the test bacteria (30), natural antioxidants did not show any activity up to 800... 

Just as the allylic alcohol group at C-17 in 33 directed tnCPBA to the more hindered face of the molecule, in this step the alcohol group at C-16 played a similar role as it ensured the initial delivery of hydride onto the more sterically shielded side of 72 at C-15. 

The target molecule must first be rotated to fit the Sharpless asymmetric epoxidation model (need to have allylic alcohol group in bottom right position). The retrosynthesis of the epoxide leads to an alkene with the stereochemistry shown. Since the oxidation has occurred at the top face, the (+) enantiomer of diethyl tartrate (DET) is required. Note that only the alkene with the aUyUc hydroxyl group is oxidized in the Sharpless epoxidation. 

Application Matsutake alcohol (a fragrance compound in a Japanese mushroom) is synthesized by reduction of one terminal double bond by LiAlH4—Cp2TiCl2 after protection of an allylic alcohol group as a diisobutylaluminium alkoxide ... 

The stereoselective branching of L-rhamnal at C-1 and C-2 via a silicon tethered radical cyclization is illustrated in Scheme 7, and allyl alcohol groups which are protected as their (bromomethyl)dimethylsilyl ethers undergo a radical-induced cyclization to give branched-chain sugars as shown in Scheme ZP... 

Similar results were obtained with acyclic mono- and sesquiterpenoid compounds containing an allylic alcohol group, either in a primary or a tertiary position. For example, linalool 9, nerolidol 10, geraniol 11, citronellol (or their estem) are hydroxylated by A. niger [5-7] and many other microorganisms [8-10] in terminal position, concurrently with epoxidation (followed by hydrolysis) at the remote double bond ... 

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