Intramolecular reactions oxymercuration

The methanol can be replaced by other nucleophilic solvents such as ethanol, acetic acid, or water (in tetrahydrofuran as cosolvent) to give the corresponding ethoxy-, acetoxy-, or hydroxy-esters. Cyclic ethers (substituted tetrahydrofurans and tetrahydropyrans) are formed by intramolecular reaction when the unsaturated ester also contains an appropriately placed hydroxy-group, even in the presence of a reactive solvent. This has been developed into a procedure for the identification, analysis, and isolation of long-chain alcohols and acids having alkene unsaturation in positions 3 (trans only), 4 (cis or tram), or 5 (cis or trans) Such acids (or natural mixtures in which they are present) are reduced to alcohols and subjected to oxymercuration (in DMF as a non-participating solvent) and demercuration. Cyclic ethers are formed only when there is unsaturation at positions 3,4, or 5 other double bonds are unaffected. For example, methyl arachidonatc... 

Stereoselective intramolecular oxymercuration of carbohydrate derivatives was proposed as the key reaction for efficient preparation of mono- and dihydroxylated unsymmetrical bis-tetrahydrofuran skeletons present in naturally occurring biologically active acetogenins. The trans- and. mz-selective intramolecular oxymercurations were explored in an enantioselective synthesis of the bis-tetrahydrofuran skeleton of mucoxin (Fig. 57).73... 

A study of the intramolecular alkoxymercuration of ( )-5-arylpent-4-en-l-ols (70) has indicated that the regioselectivity is closely related to the Hammett constants of the para-substituents on the benzene ring. Large solvent effects on the regioselectivity were also observed (Scheme 17 and Tables 2 and 3). By contrast, the related oxymercuration of -methylstyrene is 100% a-sclcctivc. This comparison shows that the regioselectivity of the intermolecular reaction is controlled by electronic factors, whereas the cyclization is governed by a delicate balance of steric and electronic effects.65... 

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. 

The intramolecular version of the oxymercuration reaction affords cyclic ethers. Furthermore, treatment of organomercury compounds (R-HgX) with NaBH4 in DMF in the presence of O2 replaces the carbon-mercury bond by a carbon-oxygen bond and yields the corresponding alcohol (R-OH). ... 

As the reasons for the diastereoselectivity of syn-selective aldol reactions are well established we will focus on the selectivity of the ring closure. We have carried out studies on intramolecular oxymercurations of a series of simple alkenols related to 8 and have found that they consistently close to give predominantly syn and not anti products (Fig. 3). 

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... 

Oxymercuration of several 18 2 esters also gave cyclic ethers when carried out in water rather flian methanol. This is not difficult to understand because the first (intennolecular) stage in the reaction should produce hydroxy monoenes some of which react further in an intramolecular fashion. Methyl linoleate (9c 12c), for example, yielded a mixture of 9,12- and 10,13-tetrahydrofurans (46%) along with several dihydroxystearates (52%). Some of the latter were subsequently cyclized by acid, raising flic yield of cyclic ethers to 70%. The isomeric 8c 12c diene gave 9,12-tetrahydrofuran (23%), 8,12- and 9,13-tetrahydropyrans (36%), and dihydroxystearates (14%). 

The problems that follow explore various synthetic aspects of oxymercuration-demercuration. Experimental procedures sometimes vary depending on the particular transformation. The source of the electrophile may be a mercury(II) salt other than Hg(OAc)2, the nucleophile may be other than H2O, and the reaction may be intramolecular rather than intermolecular. 

The proposed mechanism of the Ferrier carbocyclization reaction is oudined in Scheme 12.13. First, oxymercuration of the exo-olefin in 48 affords mercurial-hemiacetal 49, whose aglycon moiety (-OMe) eliminates to give mercurial-aldehyde derivative 50. This mercurial intermediate 50 was isolable when a stoichiometric amount of Hg salt was employed at low temperature. Intramolecular aldol-type cyclization of 50 provides product 51. 

The compound YXC=CHCH2C(CH2HgCl)CH2CH2CH2CH=>C(S02Tol) undergoes an intramolecular Michael reaction in the presence of R4NX and a Lewis acid. The stereochemical control in the intramolecular oxymercurations of 5-alken-l-ols, derived from tri-O-acetyl-D-glucal, have been studied. ... 

By reaction with silver acetate, l,n-bromohydroperoxides are converted into endoperoxides with (n-i-2) ring atoms. Similar to the classical oxymercuration, intramolecular peroxymercuration of unsaturated (homoallyhc or higher homologs) hydroperoxides can also serve as an efficient path to endoperoxides. ... 

However, before NaBH4 is introduced, 4 can also continue to react under the oxymercuration conditions, where Hg(OAc)2 can behave as a Lewis acid. As shown, the Hg(OAc)2 can interact with the oxygen atom of the epoxide group, much like an epoxide interacts with a proton, to facilitate the intramolecular nucleophilic attack by the nearby hydroxyl group. This intramolecular cyclization reaction forms a five-membered ring. A final proton transfer step, followed by the demercuration step, results in one of the major cyclization products, 8. 

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