Oxymercuration approach

Figure 15. The intramolecular oxymercuration approach as a strategy for the octosyl acids.

SCHEME 10 Oxymercuration approach to install the tertiary alcohol. 

Scheme 4.1 includes examples of oxymercuration reactions. Entries 1 and 2 illustrate the Markovnikov orientation under typical reaction conditions. The high exo selectivity in Entry 3 is consistent with steric approach control on a weakly bridged (or open) mercurinium ion. There is no rearrangement, indicating that the intermediate is a localized cation. 

Reinstallation of the fractured spiro ring can be accomplished either directly at the enone level or, more interestingly, after the ketone carbonyl has been capped as in 36. When 36 and stereoisomers thereof are individually subjected to intramolecular oxymercuration, the stereochemical course of the cyclization is dictated by the approach of Hg2+ to that surface of the double bond where coordination to a proximal axially oriented ether oxygen can operate. [31] Where 37 and 40 are concerned,... 

The approach to polyketide synthesis described in Scheme 5.2 requires the relatively nontrivial synthesis of acid-sensitive enol acetals 1. An alternative can be envisioned wherein hemiacetals derived from homoallylic alcohols and aldehydes undergo dia-stereoselective oxymercuration. Transmetallation to rhodium could then intercept the hydroformylation pathway and lead to formylation to produce aldehydes 2. This proposal has been reduced to practice as shown in Scheme 5.6. For example, Yb(OTf)3-cata-lyzed oxymercuration of the illustrated homoallyhc alcohol provided organomercurial 14 [6]. Rhodium(l)-catalyzed hydroformylation of 14 proved successful, giving aldehyde 15, but was highly dependent on the use of exactly 0.5 equiv of DABCO as an additive [7]. Several other amines and diamines were examined with variation of the stoichiometry and none proved nearly as effective in promoting the reaction. This remarkable effect has been ascribed to the facilitation of transmetallation by formation of a 2 1 R-HgCl DABCO complex and the unique properties of DABCO when both amines are complexed/protonated. 

Phenols add intramolecularly to Michael acceptors. " Under acidic conditions, a one-pot sequence starts with initial electrophilic acetylation of the activated aromatic ring and is followed by cyclization." With an appropriate leaving group in the /f-position (OMe. or other amines such as in the unsaturated carbonyl compound (e.g., 4) is formed. Other approaches to pyroncs include the self-condensation of protected //-hydroxy acrylates,intramolecular aldol reactions followed by condensation,thermal cycli-zations of unsaturated ()-chloro esters,and an iodo-cyclization-elimination sequence w th Michael acceptors.Oxymercuration of an unsaturated alcohol is an alternative cyclization approach to tetrahydropyrans. 

Zhao and co-workers 48) reported the first synthesis of homoharringtonine (3) in 1980 (Scheme 20). Unsaturated keto acid 151, prepared either from 5,5-dimethyl-5-valeroIactone 150, or by chain extension from the commercially available bromide 149, was esterified with cephalotaxine to give the cephalotaxyl derivative 152, which reacted with methyl bromoacetate under Reformatsky conditions to yield a mixture of epimers of dehydro-homoharringtonine 153. This mixture was converted to homoharringtonine and its epimer by means of oxymercuration, as well as by acid catalysis. As in the aforementioned syntheses of harringtonine, the Reformatsky reaction proceeded with no stereoselectivity, and diastereomeric mixtures resulted from all of these approaches. 

In preliminary studies we have found that this is also a powerful approach to the preparation of enantiomerically pure complex spiroacetals (Fig. 22 [23,24]). Intramolecular oxymercuration of 84 proceeds efficiently, although without any stereoselectivity. 

The allyl alcohol 56 furnished 58 predominantly on oxymercuration in aqueous tetrahydrofuran followed by reductive demercuration using NaBH4 [31]. Assisted by chelation with both the ring oxygen and the carbinol function, mercuration on the a-face allows water to approach from the p-face, as shown in 57, to form the product 58 selectively. In aligning the methyl group on the double bond with the... 

By the approach B Stetter and coworkers successfully synthesized in 1966 the first 2,6-dihetero-adamantane, the 2,6-dioxa-adamantane (14). Oxymercuration of... 

Scheme 9. Stereoselective intramolecular oxymercuration-demercuration approach (46). Reagents and conditions (a) Hg(OAc) (b) aq. NaOH NaBU, n-Bu4NOH.

The challenge to the synthetic chemist that was posed by these structures was the control of C6 stereochemistry. An early solution to this problem involved the intramolecular oxymercuration-demercuration approach, as illustrated in Scheme 9 (46,58). Thus, the stereoselective cyclization of 38 to the tricycUc cannabinoid skeleton by means of the intramolecular oxymercuration-demercuration reaction (58,61) gave the 6P-isomer predominantly (6P 6a = 85 15). The enantiomers were separated by chiral high-performance liquid chromatography (HPLC) using Chiralpak OD columns. The probable... 

The structure of the intermediate in oxymercuration has received much attention and can be approached by considering what is likely to happen when the electrophile HgOAc reacts with the double bond of an alkene. 

Acid-catalyzed hydration proceeds with Markovnikov addition (Section 9.4). That is, the hydroxyl group is positioned at the more substituted carbon. It is a useful method if the substrate is not susceptible to carbocation rearrangements (Section 6.11). In a case where the substrate can possibly rearrange, oxymercuration-demercuration can be employed. This approach also proceeds via Markovnikov addition, but it does not involve carbocation rearrangements. Hydroboration-oxidation is used to achieve an Markovnikov addition of water. 

Oxymercuration is the key reaction in an interesting approach to 2,6-dimethyl-18-crown-6 from diallyl ether and tetraethylene glycol (Scheme 48). Some new optically active macrocycles (90) have been prepared that use as the chiral... 

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