Alkenes hydroxyl group directing effect

An interesting variant involves the use of an allylic alcohol as the alkene component. In this process, re-oxidation of the catalyst is unnecessary since the cyclization occurs with /Uoxygen elimination of the incipient cr-Pd species to effect an SN2 type of ring closure. Both five- and six-membered oxacycles have been prepared in this fashion using enol, hemiacetal, and aliphatic alcohol nucleophiles.439,440 With a chiral allylic alcohol substrate, the initial 7r-complexation may be directed by the hydroxyl group,441 as demonstrated by the diastereoselective cyclization used in the synthesis of (—)-laulimalide (Equation (120)).442 Note that the oxypalladation takes place with syn-selectivity, in analogy with the cyclization of phenol nucleophiles (1vide supra). 

On the other hand, H.B. Henbest realised that adjacent polar functional groups have a directing effect on the epoxidation of alkenes as well as on other related reactions [2]. A very well known example is the 5yn-directing effect of an ally lie hydroxyl group in epoxidations of cyclic alkenes (Scheme 10.1) ... 

The cyclopropanation is sensitive to steric effects, adding from the less-hindered face. Having a neighboring hydroxyl group will generally accelerate the reaction, and will direct the cyclopropanation syn to the hydroxyl group even into sterically congested alkenes. 

In 2008, Blechert et al. reported the total synthesis of e/jt-lepadin F (89) and G (90) by a tandem ene-yne-ene RCM [74]. Lepadins are members of marine alkaloids with decahydroquinoline framework. As a key step in their synthesis (Fig. 26) they planned to construct the decahydroquinoline core skeleton by a selective tandem ene-yne-ene RCM of the dienyne precursor (91). Craiceivably, two different reaction pathways could be expected (1) initiation of metathesis may occur at the terminal double bond followed by two consecutive RCMs to afford the desired 6/6 bicycle (92) or (2) initiation may occur on the disubstituted alkene followed by tandem RCMs to produce the undesired 5/7 bicycle (93). Considering the preference of initiation on monosubstituted double bond as well as the directing effect of free hydroxyl group, pathway (1) may be more favored. Gratilyingly, treatment of dienyne (91) with 10 mol% Gmbbs I catalyst smoothly provided the desired 6/6 bicycle (92) in 90% yield. 

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