Z-Allylic alcohols

Furthei-more, the cyclization of the iododiene 225 affords the si.x-membered product 228. In this case too, complete inversion of the alkene stereochemistry is observed. The (Z)-allylic alcohol 229 is not the product. Therefore, the cyclization cannot be explained by a simple endo mode cyclization to form 229. This cyclization is explained by a sequence of (i) e.vo-mode carbopallada-tion to form the intermediate 226, (ii) cydopropanation to form 227. and (iii) cyclopropylcarbinyl to homoallyl rearrangement to afford the (F3-allylic alcohol 228[166]. (For further examples of cydopropanation and endo versus e o cyclization. see Section 1.1.2.2.)... 

The simple and elegant tactic of cleaving the acetoxythioacetal function in 29 either with or without concomitant epimerization at C-2 effectively avoids the problematic (nonstereoselective) epoxi-dation of chiral Z allylic alcohols such as 12-Z (see Scheme 9). 

The development of Sharpless asymmetric epoxidation (SAE) of allylic alcohols in 1980 constitutes a breakthrough in asymmetric synthesis, and to date this method remains the most widely applied asymmetric epoxidation technique [34, 44]. A wide range of substrates can be used in the reaction ( ) -allylic alcohols generally give high enantioselectivity, whereas the reaction is more substrate-dependent with (Z)-allylic alcohols [34]. 

An extension of this method can be used to prepare allylic alcohols. Instead of being protonated, the (3-oxido ylide is allowed to react with formaldehyde. The (J-oxido ylide and formaldehyde react to give, on warming, an allylic alcohol. Entry 12 is an example of this reaction. The reaction is valuable for the stereoselective synthesis of Z-allylic alcohols from aldehydes.245... 

Lithiation of the vinylstannane moiety of 22 with BunLi followed by the reaction with PhCHO gives (Z)-7-silyl allylic alcohol 23 (Scheme 65).261 The subsequent Cu(i)-mediated cross-coupling with allyl chloride affords (Z)-allylic alcohol 24 with the (Z)-stereochemistry retained. 

In the case of (Z)-allylic alcohol 13, however, it takes 2 weeks to get product 14 in a ratio of 14 15 = 30 1 for matched pairs, while the epoxide 14 is obtained in the much lower ratio of 14 15 = 3 2 for mismatched pairs (Scheme 4 5). 

Use of poly(octamethylene tartrate) in place of dialkyl tartrates offers practical utility since the branched polymers yield hetereogeneous Ti complex catalysts which can be removed by filtration. Overall the work-up procedure is considerably simplified relative to the conventional Sharpless system. In addition, significant induction is shown in the epoxidation of (Z)-allylic alcohols[7] and even with homoallylic[8] species where the dialkyltartrates give very poor results Figure 5.3. Table 5.2 is illustrative of the scope using the polymer ligand. 

Figure 5.3 Oxidation of some (Z)-allylic alcohols and some homoallylic alcohols using poly(tartrate).

Unlike with sodium borohydride (see Section 11.01.5.2), pyrrolizin-3-one 2 reacts with lithium aluminohydride mainly as an amide. No conjugate addition occurs, and only the reductive lactam cleavage takes place to give stereoselectively the (Z)-allylie alcohol 77. Similarly, benzo-annulated pyrrolizin-3-one 17 gives the corresponding benzylic alcohol 78. The same reactivity was observed with organometallics such as methyllithium which gives exclusively the tertiary (Z)-allylic alcohol 79 (Scheme 7). 

With Rh(I)/PF-PPh2, reactions of Z-allylic alcohols generally afford higher enantios-electivity than the corresponding E-isomers. We applied this process to formal total syntheses of (-)-7-hydroxycalamenene and (-)-7-hydroxycalamenenal [8], two naturally occurring sesquiterpenes in the cadinene family (Eq. 7). 

Olefins that lack an aromatic substituent can also be isomerized by Rh(l)/PF-P(o-To1)2 with good enantioselectivity (Eq. 8). Interestingly, for this class of substrates the reactions of E- and Z-allylic alcohols proceed with similar enantioselection. 

I 4 Recent Advances in Rhodium( )-Cata yzed Asymmetric Oiefin Isomerization Tab. 4.2 Rh(l)/PF-P(o-Tol)2-catalyzed isomerization of Z-allylic alcohols. 

This problem was solved by Adam and coworkers in 1994-1998. They presented a high-yielding and diastereoselective method for the preparation of epoxydiols starting from enantiomerically pure allyhc alcohols 39 (Scheme 69). Photooxygenation of the latter produces unsaturated a-hydroxyhydroperoxides 146 via Schenck ene reaction. In this reaction the (Z)-allylic alcohols afford the (5, 5 )-hydroperoxy alcohols 146 as the main diastereomer in a high threo selectivity (dr >92 8) as racemic mixmre. The ( )-allylic alcohols react totally unselectively threolerythro 1/1). Subsequent enzymatic kinetic resolution of rac-146 threolerythro mixture) with horseradish peroxidase (HRP) led to optically active hydroperoxy alcohols S,S) and (//,5 )-146 ee >99%) and the... 

Achiral ester-substituted nitrones as well as chiral nitrones can be employed in diastereoselective asymmetric versions of tandem transesterification/[3 + 21-cycloaddition reactions, as shown in Scheme 11.54 (174). High diastereoselectivity and excellent chemical yields have been observed in the reaction with a (Z)-allylic alcohol having a chiral center at the a-position in the presence of a catalytic amount of TiCl4- On the other hand, the reaction with an ( )-allylic alcohol having a chiral center at the a-position, under similar conditions, affords very low selectivities. Tamura et al. has solved this problem with a double chiral induction method. Thus, high diastereoselectivity has been attained by use of a chiral nitrone. 

In this type of study, the terminally-CF3 propargylic alcohol (S)- derived from the enzymatic resolution is also a useful intermediate. This material is transformed into the corresponding E- and Z-allylic alcohols after successful enzymatic optical resolution. Os04-catalyzed oxidation eventually led to the formation of the desired triols 30 in a diastereoselective manner. 

Reaction with isoprene epoxide. Alkyllithium reagents undergo 1,4-addition to isoprene epoxide to give predominately (Z)-allylic alcohols, particularly in the presence of a base (equation I). The reaction was used to prepare a-santalol (I) from n-bromotricyclene. 

Kinetic resolution of chiral aUylic alcohols.7 Partial (at least 60% conversion) asymmetric epoxidation can be used for kinetic resolution of chiral allylic alcohols, particularly of secondary allylic alcohols in which chirality resides at the carbinol carbon such as 1, drawn in accordance with the usual enantioface selection rule (Scheme I). (S)-l undergoes asymmetric epoxidation with L-diisopropyl tartrate (DIPT) 104 times faster than (R)-l. The optical purity of the recovered allylic alcohol after kinetic resolution carried to 60% conversion is often > 90%. In theory, any degree of enantiomeric purity is attainable by use of higher conversions. Secondary allylic alcohols generally conform to the reactivity pattern of 1 the (Z)-allylic alcohols are less satisfactory substrates, particularly those substituted at the /1-vinyl position by a bulky substituent. 

However, epoxides derived from (Z)-allylic alcohols react slowly with the same reagents and with lower regioselectivity. 

Before adding aldehyde 14 a transmetalation from zirconium to zinc is necessary because of low reactivity of the sterically hindered organozirconocene compounds like 18 toward most organic electrophiles.9 Resulting alkenylethylzinc 19 reacts in a 1,2-addition with the cr,y3-unsaturated aldehyde 14 transferring exclusively the alkenyl moiety. The formation of Z -allylic alcohol 20 reveals stereochemical retention of the double bond configuration in the transmetalation and addition steps. 

The Z-allylic alcohol below dehydrates in acid solution to the -diene. We have lots of data on this mechanism, all summarized in the diagrams. You may like to note as well that the product contains no deuterium after dehydration in D20. 

The direct use of the vinyl lithium species generated from 2 preferentially afforded the Z-allylic alcohol in the coupling process c. Explain the change in stereoselectivity. 

Kobayashi et al. successfully performed asymmetric cyclopropanation using substoichio-metric amounts of catalyst 45 (Scheme 9). [32] The levels of enantioselectivity achieved are in the 70-90 % range. Both, E- and Z-allylic alcohols are readily converted. Vinylstannanes 46 are also appropriate substrates. The resulting enantio-merically pure cyclopropanated stannanes hold great synthetic potential [33]. Thus, the cyclopropanated stannane 48 can be converted into the substituted cyclopropane 49 after successful tin-lithium exchange and electrophilic substitution. 

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