Adamantanones 5-substituted

In the present study isomorphic substitution of Al with Sn [11-13] in the silicalite framework was attempted in order to induce catalytic functionalities and these catalysts was studied for Baeyer-Villiger oxidation of 2-adamantanone and norboranone. 

Hahn and le Noble have discovered strongly enhanced stereoselectivity in the reduction of 5-substituted adamantanones where the substitution at C5 is by positive nitrogen (Hahn, J. M. le Noble, W. J., J. Am. Chem. Soc., 1992, 114, 1916). Thus E/Z ratios for borohydride reduction of compounds 1-3 were in the range 20-25. Suggest a possible reason for these observations on the basis of orbital interaction theory. 

On p. 754 it was mentioned that electronic effects can play a part in determining which face of a carbon-carbon double bond is attacked. The same applies to additions to carbonyl groups. For example, in 5-substituted adamantanones ... 

Adamantanone is a very versatile starting material for the preparation of adamantane derivatives, especially those substituted at secondary carbon atoms. 

The chirality of (15 )-2-adamantanone-4-13C (87) and (lS )-2,4-adamantanedione-4-13C (88) is solely due to 13C substitution. Since the 13C ring carbon of 87 is located in a positive octant, from the negative Cotton effect of 87, it follows that 13 C makes a smaller contribution than 12C. Diketone 88 exhibits three CD bonds with remarkably large amplitudes, which were attributed to different n - tt transitions195. 

Since the adamantane ring system is composed of three interlocking cyclohexane rings, all in the perfect chair conformation, /3-sub stituted adamanta-nones are also ideal models for establishing quantitative substituent contributions to the optical rotatory dispersion of cyclohexanones in the undisturbed chair form. A variety of optically active /3-equatorial and /3-axial substituted adamantanones have been synthesized 18°-184) and their circular dichroism determined 184-185) jji generai) axial polar substituents (C02R, Cl,... 

Under special conditions, an ionic substitution reaction also provides a convenient method for the funtionalization of the methylene positions of adamantane. Treatment of adamantane or 1-hydroxyadamantane with 96 % H2S04 at 77 °C for 5 hours results in a 50—60% yield of adamantanone 67-69). 

The reported 2731 yield of adamantanone oxime from this reaction (63 %) is misleading since it is based on Cl2 as the limiting reagent. Careful product analyses have shown that the overall ratio of tertiary to secondary substitution products ( 2) is quite normal275), While this reaction is clearly much less useful for the preparation of methylene substituted adamantanes than the ionic processes discussed above, it may be applicable in more specialized cases such as, for example, the synthesis of polyalkylsubstituted adamantanones where the ionic processes work poorly. 

Rearrangements of substituted protoadamantyl derivatives (see Section III.A) also appear to provide attractive routes to 1,2-disubstituted adamantanes. This is illustrated by the acid catalyzed rearrangement of the isomeric 4-methyl-4-protoadamantanols to l-methyl-2-adamantanone in near quantitative yield (Eq. (71))42>76). 

The second route to 2,4-disubstituted adamantanes involves a 7r-route ring closure of substituted bicyclo[3.3.1]nonenes. Thus, lactone 85 28S) rearranges in 50 % sulfuric acid to 4-hydroxy-2-adamantanone (86) via the acylium ion 87 278>. Adamantanone oxime rearranges in 96 % sulfuric acid to 86 (mixture of isomers) in an analogous manner 109h Similarly, the Schmidt reaction of... 

Gung, B. W. Structure Distortions in Heteroatom Substituted Cyclohexanones, Adamantanones, and Adamantanes, Chem. Rev. 1999,99,1377-1386. 

On p. 1023, it was mentioned that electronic effects can play a part in determining which face of a carbon-carbon double bond is attacked. The same applies to additions to carbonyl groups. For example, in 5-substituted adamantanones (2) electron-withdrawing (-/) groups W cause the attack to come from the syn face, while electron-donating groups cause it to come from the anti face. In 5,6-disubstituted norborn-2-en-7-one systems, the carbonyl appears to tilt away from the 7i-bond, with reduction occurring from the more hindered face. An ab initio study of nucleophilic addition to 4-ferf-butylcyclohexanones attempted to predict 7i-facial selectivity in that system. ... 

It is of considerable interest to establish the magnitude of electronic effects on facial selectivity. The symmetry of 2-adamantanone (1 X=H) makes this structure ideal [61] to investigate electronic effects on transition state energy, since the faces of the carbonyl are little affected by steric and torsional effects with substitution at C5. The donor and acceptor ability of the four adjacent carbon-carbon bonds to the carbonyl can be varied without significantly altering the molecular structure. 

The results of experiments on the reduction on 5-substituted adamantanones 1 and 5-azaadamantan-2-one N-oxide (2) with NaBHq show that electron-withdrawing substituents favour attack by the complex hydride syn to the substituent or nitrogen [30, 34, 51] (Fig. 6-17). In the case of 2, the effect is striking, with a synlanti attack ratio of 96/4 for the formation of the anti syn alcohols respectively (Table 6-1). Electron-donating substituents show a marginal preference for anti attack. Similarly, syn facial selectivity is found in free-radical reactions [63], ther-... 

Calculations on the Reduction of 5-Substituted Adamantanones with AlHj 177... 

Chung and Ho have reported the details of the photochemical addition of electron-deficient alkenes to the substituted adamantanones (73). All of the ketones undergo reaction from the singlet state and, for example, the addition to acrylonitrile affords the two adducts (74) and (75) in an anti syn ratio of 60 40 which is the approximate value for the products of all systems studied. The irradiation at 300 nm of the alkene (76) in neat spectral-grade acetone affords (77), referred to as a photo-Conia product, in 52% yield. A trace of the oxetane (78) was also found. In hexadeuterioacetone the ratio of the products was found to be 2 1... 

However, the stereoselective reductions of the 5-substituted adamantanones 3.50 [CT2, G5, KA4, LL5], and bicyclo-[2.2.2]-octan-2-one 3.51 [MK5] have been interpreted in terms of Cieplak s model [C6, CT3]. Unfortunately, the observed stereoselectivities are low (de <40%), so that it is difficult to dissect the various parameters involved in such reductions [CHS, N2], The electronic contribution to the stereoselectivity of the reduction of substituted 9-benzonorbomenones 3.52 is very important [G5, OTl, OT2] (Figure 3.20). Halogen substituents on the aromatic ring favor syn attack by all hydrides on those very rigid systems. Electrostatic effects have been invoked to interpret these results [PW2, WTl]. 

Reaction with adamantanone. Japanese chemists1 treated adamantanone (1) with sodium azide in methanesulfonic acid with the expectation of achieving the Schmidt reaction. However, the unexpected 4-methylsulfonoxyadamantanone was obtained in 90% yield. Alkaline hydrolysis cleaves (2) to A2-bicyclo[3.3.1]-mmcnc-7-carboxylic acid (3) in 85% yield by a quasi-Favorsky reaction. Adaman-lanc itself does not undergo this unusual substitution reaction. 

The 5-substituted 2-adamantanones constitute a class of molecules belonging to the category of 4-substituted cyclohexanones. William le Noble studied the reduction of several of this class of compounds by different hydride sources and noted the selectivity profile. These results are collected in Table 5 [18]. Although the reaction conditions are not exactly the same for direct comparison of the results... 

Table 5 Stereochemical outcome of nucleophilic additions to 5-substituted 2-adamantanones O...

Peterson aikenation of carbonyl compounds with trimethylsilylmethoxymethyl carbanion (14) can also give enol ethers. An example is the reaction of (14) with adamantanone. Another method of alkene synthesis is the elimination of CO2 and H2O from a P-hydroxycarboxylic acid. If the carboxylic acid is substituted by an a-alkoxy group, the reaction can be used for the synthesis of enol ethers, as illustrated in Scheme 4. ... 

Substituted l,2,4-trioxan-5-ones also show high thermal stability <93H(35)725>. Typically, the flash vacuum thermolysis of (46) goes to completion at temperatures of 3 50-400 °C giving adamantanone (47), cyclohexanone (48) and carbon dioxide (Equation (2)). 

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