Oxymercuration Studies

Other oxymercuration studies include those on the monoepoxide of cw,c/5-cyclo-octa-l, 5-diene, with neighbouring group participation of the oxiran oxygen, bicyclo[2,2,2]octene, cis- and rranj -cyclo-octenes and cyclononenes, 1,3-diphenylpropenones, and the bicyclic systems (492) and (493). The kinetics of methoxymercuration of substituted cinnamic acids and many aliphatic olefins have been measured. 

Oxymercuration studies on optically active penta-2,3-diene using mercuric acetate in methanol suggest that formation of the unsymmetrical mercurinium... 

The best characterized of these reactions involve the mercuric ion, Hg ", as the cation. The same process occurs for other transition-metal cations, especially Pd, but the products often go on to react fiirther. Synthetically important reactions involving Pd will be discussed in Section 8.2 of Part B. The mercuration products are stable, and this allows a relatively uncomplicated study of the addition reaction itself The usual nucleophile is the solvent, either water or an alcohol. The tenn oxymercuration is used to refer to reactions in... 

Klein showed that axial reaction of the parent methylenecyclohexane 37 is preferred in hydroboration [106], The experimental data on the parent methylenecyclohexanone 37a accumulated by Senda et al. [107] and the more recent systematic studies by Cieplak et al. [108, 109] on jr-facial selectivities of 3-substituted methylene-cyclohexanes 37 have characterized the intrinsic features of the facial selection of methylenecyclohexanes. That is, axial preference of unsubstituted and 3-substituted methylenecyclohexanes was observed in oxymercuration [107] and epoxidation reactions [110], There is also an increase in the proportion of axial attack with increase in the electronegativity of the remote 3-equatorial... 

Formation of mixtures of products in these reactions can be attributed largely to the properties of the acetate group. The reactions of a number of cycloalkenes with thallium(III) salts have been investigated in some detail and the results obtained have served both to elucidate the stereochemistry of oxythallation and to underline the important role assumed by the anion of the metal salt in these oxidations. The most unambiguous evidence as to the stereochemistry of oxythallation comes from studies by Winstein on the oxythallation of norbornene (VII) and norbornadiene (VIII) with thal-lium(III) acetate in chloroform, in which the adducts (IX) and (X) could be precipitated from the reaction mixture by addition of pentane 128) (Scheme 11). Both by chemical means and by analogy with the oxymercuration... 

From the evidence currently available it appears that the mechanism of oxythallation is similar to that of oxymercuration. That is, initial rapid formation of a 7r-complex—a thallinium ion—followed by rearrangement of this species to give a o-bonded organothallium derivative (54). Decomposition of this latter intermediate by one or more of the processes shown in Scheme 8 then leads to products. The results obtained from a number of kinetic studies are in broad general agreement with this interpretation (52,79). 

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... 

A study is now underway to evaluate completely the future synthetic role of the oxymercuration—ozonolysis sequence. 

The carbon-metal systems considered appropriate for this section (and not covered elsewhere in this series) are carbon-tin, carbon-mercury and, to a restricted extent, carbon-palladium bonds. Although or-ganomercurials and organostannanes have been studied for over a century, the former continue to attract attention because of their controlled formation by the Markovnikov oxymercuration reaction (OM) and its variants, and the latter because of newer and regiospecific methods for forming C—Sn bonds and oxidatively cleaving them. In both cases, signiticant examples of synthetically useful oxidations have... 

The quenching of the oxymercuration has also been studied, and treatment of mercurials with copper(I) chloride has been found superior to the method using sodium chloride or potassium bromide, in order to minimize the reversion of the reaction to give the starting alkene117. 

The ratio of the two products is primarily affected by the nature of the mercury(II) salt and also by the reaction conditions. Since the formation of these compounds could result from either a kinetically or a thermodynamically controlled mercuration process, a study of the mercuration of 3 in the presence of aromatic amines using various mer-cury(II) salts has been more recently carried out in order to determine the conditions under which aminomercuration is reversible, and the results have been compared to those of the oxymercuration . 

Markownikoff hydration of olefins (2, 265-267). Brown and Geoghegan1 have reported a detailed study of the oxymercuration-demercuration procedure. Yields of alcohols in the case of terminal olefins, RCH=CH2 and R2C=CH2, and disubstituted internal olefins, RCH=CHR are practically quantitative. Tri-substituted olefins of the type R2C=CHR show a wide variation in reactivity. 1 -Phenylcyclopentene and 1 -phenylcy clohexene, for example, are unreacti ve. 

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). 

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 evidence for this mechanism includes the fact that the course of the reaction can be diverted by oxygen, an efficient radical scavenger. Also, the stereochemistry of the reduction, as studied by using NaBD4 as the reducing agent, is consistent with a radical intermediate. For example, a 50 50 mixture of erythro- and threo-3-deuterio-2-butanol is obtained by oxymercuration of either cis- or trans-2-butene, followed by reduction with NaBD4 ... 

The oxymercuration-demercuration of 3,3-dimethyl-1-butene is a striking example illustrating this feature. It is in direct contrast to the hydiadon of 3,3-dimethyl-1-butene we studied previously (Section 8.4B). 

Jernow et aV have obtained evidence for the participation of ether groups in oxymercuration reactions, although rate studies (Table 10) show that ether groups provide less anchimeric assistance than hydroxyl groups... 

In a related study, high ds-selectivities were obtained with trialkylsilyl-protected substrates when the ring formation was initiated by oxymercuration prior to the Pd-catalyzed carbonylation stepP ... 

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