Intramolecular oxymercuration

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... 

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,... 

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

Trioxanes were prepared through the intramolecular oxymercuration of various allylic peroxyhemiacetals and peroxyhemiketals . For example, 1,2,4-trioxanes... 

Silver(I) catalyzed cyclizations of allenic alcohols (202) lead to 2,5-dihydrofurans (203) (79S743), whilst another mild method for the synthesis of tetrahydrofurans is the intramolecular oxymercuration-demercuration process. Geraniol, when treated with mer-cury(II) acetate and subsequently with sodium borohydride, gave a tetrahydrofuran. 

Use of remote allylic silyl ethers, such as 72b,c, rather than of allylic alcohol 72a in intramolecular oxymercurations leads to a higher 1,3-syM-diastereoselectivity (equation 34)47. The overall yields for syn-Ti and anti-14 range between 85-93%. The best selectivity reaches 7 1 involving the (t-BujPl Si group (entry 36 of Table 1). 

Intramolecular oxymercuration of allene 299 followed by Pd(II)-catalysed carboxymethylation has been found to proceed with excellent cis/trans selectivity (>98 2), presumably via the least hindered transition state 300421. 

Intramolecular oxymercuration. Oxy mercuration of 1 with mercury(II) pivalate followed by reduction of the intermediate mercury complex results in 2, isolineatin. 

Conversion of synthetic picrotoxinin (1) to picrotin (2) was achieved by Corey and Pearce in four steps and 30% overall yield 124). To prevent intramolecular oxymercuration, the tertiary alcohol of picrotoxinin (1) was protected as trifluor-oacetate 346 prior to addition of mercury trifluoroacetate in a benzene/THF mixture as solvent. Demercuration with sodium borohydride failed, thus the covalent C-Hg bond was cleaved by tributylstannane in ethanol. Mild hydrolysis of the bistrifluor-oacetate 347 afforded picrotin (2) in 30% overall yield (75% corrected for recovered 1) from picrotoxinin (1). 

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). 

Fig. 7). The ring closure also proved to be remarkably stereoselective. Thus intramolecular oxymercuration, followed by reductive demercuration, provided the tetrahydropyran (22, ring A of X-206) with the desired 2,6-cis-relative stereochemistry in excellent overall yield as a single diastereomer. 

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. 

To show the way in which one of the piperidine isomers was synthesized and how each was utilized to make heteroyohimbine alkaloids, the full synthesis of ( )-tetrahydroalstonine (44a) and ( )-akuammigine (44b) is detailed in Scheme 11. As well as the effective dehydrogenation of the ethyl group, notable in the sequence is the intramolecular oxymercuration, (45) — (46), which in the cis-series leads, by kinetic control, only to the 19 -isomer. Also of interest is the absence, apparently, of inside isomers (such as have been reported in other similar cyclizations, see below) in the closure of the C-ring, i.e. (47) — (44). 

An intramolecular oxymercuration is used to control the stereochemistry at C-6 in the formation of smne cannabinol analogues (94T2671). 

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... 

Fatty acids having double bonds close to the carboxyl end can be distinguished by using methods based on the intramolecular oxymercuration of alcohols derived from the acids. Double bonds which are 3t, 4c/t or 5dt can be identified in this way (Gunstone and Inglis, 1973). 

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. ... 

D.K. Mohapatra, S. Mohapatra, M.K. Gurjar, Double intramolecular oxymercuration stereoselective synthesis of highly substituted fcis-tetrahydrofuran. Tetrahedron Lett. 47 (2006) 5943-5947. 

Metal-activated alkene additions can be classified as stoichiometric or catalytic processes. Stoichiometric processes for THP synthesis typically involve the use of mercury(II) salts and to a lesser extent iodo and seleno reagents. The progress of intramolecular oxymercuration is determined by the stabiUty of the cationic intermediates. Product stereochemistry is under substrate control and usually leads to the thermodynamically more stable THP product. Catalytic variations generally involve palladium complexes [44], but other transition metals are becoming more common (e.g., Pt [45], Ag [46], Sn [47], Ce [48]). The oxidation state of Pd determines the catalyst reactivity. Palladium(O) complexes are nucleophilic and participate in tetrahydropyran synthesis through jt-allyl cation intermediates, whereas Pd(II) complexes possess electrophilic character and progress through a reversible t-complex. 

Alternatively, an intramolecular oxymercuration/reduction sequence can be used to effect spirocyclization with endocyclic enol ethers [77]. This method was recently used by Tan and coworkers [78] in their synthesis of acortatarin A (Scheme 33). 

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