Adamantan-2-ones

Facial selectivity of 5-substituted adamantan-2-ones (6) was initially studied by Giddings and Hudec [62], followed by intensive studies by le Noble s group [63-66]. Electron-withdrawing substituents such as phenyl (6b), fluoro (6c), hydroxyl and trifluoromethyl groups at the 5 position favored the syn addition... 

The carbonyl n face of the adamantan-2-one with an electron-withdrawing group at the 5-position is nnsynunetrized by interaction of the P o bonds antiperiplanar to the C-H bonds and to the C-R bond. The orbital phase environment of the carbonyl n orbital (7) is nnsynunetrized by the more electron-donating orbitals at the P-position, which is consistent with the observed syn preference. 

More recently, and based on the same concept, O Neill and coworkers have prepared a series of related systems (80a-c) based on Vennerstrom s adamantyl trioxolane unit". These derivatives, which are synthesized in only three steps from adamantan-2-one, have activity in the low nanomolar region (<3 nM versus K1 P. falciparum). Like the prototypes synthesized by the groups of Meunier" and Singh", these compounds can be formulated as water-soluble salts and it is anticipated that these agents may have the capacity to hit the parasite by two distinctive mechanisms. Indeed, any chemical or metabolic degradation of the endoperoxide bridge in these compounds will result in metabolites that may still have the ability to function as inhibitors of heme polymerization provided that they do not become covalently attached to proteins in the bioactivation process. 

Schippers and Dekkers reported on the CD and circularly polarized fluorescence of 4,4-dideuterio-adamantan-2-one (85)193. The CD of 85 originates in transitions to a totally symmetric n -+ n excited state with double minimum potential in the C=0 out-of-plane bending mode. 

FMO calculations using PM3-C1 were used to investigate the regioselectivities obtained by the photochemical reactions between 2-pyridone and pcnta-2,4-dienoate.46 The hard and soft acid-base principle has been successfully used to predict product formation in Patemo-Buchi reactions.47 The 2 + 2-photo-cycloaddition of homobenz-valene with methyl phenylglyoxylate, benzyl, benzophenone, and 1,4-benzoquinone produced the corresponding Patemo-Buchi products.48 The photo-cycloaddition of acrylonitrile to 5-substituted adamantan-2-ones produces anti- and svn-oxetanes in similar ratios irrespective of the nature of the 5-substituent49... 

The relative rates and stereochemistry of epoxidation reactions of 5-substituted-adamantan-2-ones with two sulfur ylids (methylenedimethylsulfurane and its oxy-sulfurane analogue) have been studied in DMSO and in benzene.318... 

The stereochemistry and reactivity of sulfur ylides with 5-substituted adamantan-2-ones has been reported in different solvents.54 The electronic perturbative effect of substituents was found to depend on the solvent and reactant. 

Reaction with ketone and imine functionalities was studied in detail for silylene 85. Reaction of this silylene with ketones such as benzophenone, 3,3-dimethylbutan-2-one, and 2-adamantan-2-one afforded the disilaoxetane compounds 139 in high yields (Scheme 15). The formation of these products most likely occurs via a [2+1] cycloaddition to form a short-lived oxasilacyclopropane intermediate 140, which further reacts with a second silylene to form the final product C19970M4861, 1997PS537>. 

Catalytic reactions were performed in CH2C12 under an 02 atmosphere Zn was used as an electron source and acetic acid as a proton donor (14). Under these reaction conditions ([2] [substrate] = 1 125), the production of adamantan-l-ol (248%), adamantan-2-ol (50%), and adamantan-2-one (108%) was observed. With cyclohexene as substrate, a mixture of cyclohexanol (54%), cyclohexanone (73%), and cyclohexene oxide (20%) was generated. In a similar experiment with cyclohexane, cyclohexanol (99%), and cyclohexanone (84%) were obtained. The product distribution is inconsistent with a free radical process for ada-mantane, the 3°/2° carbon reactivity ratio is 2.2. Control experiments demonstrated that both Zn dust and acetic acid were necessary, whereas larger quantities of acetic acid quenched the reaction (Table II). This may be due to the acidolysis of the n-oxo bond. Simple monomeric complexes such as FeClTPP (TPP is tetraphenylporphin), Fe(acac)3 (acac is acetylacetonate), and [Fe(HBpz3)2]+, 3, were inactive as catalysts under identical conditions. Furthermore, [Fe3+(Salen)]20, 1, did not show any reactivity. 

When used as a catalyst in the presence of Zn dust and excess hfacac, 4 gave high turnover numbers in CH2Cl2 for a variety of substrates (Table III). Under these conditions ([4] [substrate] hfacac = 1 1106 287), adamantane gave admantan-1 and -2-ols (turnover numbers 46.6 and 1.7, respectively) and adamantan-2-one (trace), whereas cyclohexane... 

As a rather special case, alkyl aldehydes are reduced with titanocen dichloride to the hydrocarbons through a titanium-bonded alkenic intermediate as shown by a deuterium-labeling experiment. Thus, dodecanal was converted to dodecane in 71% yield, along with dodecan-I-ol in 15-20% yield alkyl ketones such as adamantan-2-one and dodecan-6-one afforded alcohols as the major products. No reduction occurred in the case of aryl aldehydes where alkene formation is impossible. ... 

This theory is simple to apply and accounts for many experimental observations, with the proviso that there are likely to be situations where steric effects predominate. The Cieplak hypothesis is also supported by le Noble s work on 5-substituted adamantan-2-one attack of nucleophiles occurs at the syn face if the 5-substituent is an electron-withdrawing group [33] and at the anti face if it is a donor (see later section) [34]. A serious problem with the Cieplak analysis, which is relevant to all systems where this hypothesis has been applied, concerns the large energy difference between the adjacent CT-orbital(s) and the a orbital of the transition state, which will result in a minimum of orbital mixing and stabilisa-tion/destabilisation, and this is discussed in more detail later [35-38]. 

To the best of our knowledge, there is only one example in the literature of a photoaddition reaction influenced by CD and involving two different molecules, that is, the photocycloaddition of 5-X-adamantan-2-ones (X = F, Cl, Br, OH, phenyl, ferf-butyl) with fumaronitrile (Scheme 31) [319]. The reaction performed in p-CD aqueous solution led to a remarkable change in product distribution with respect to that found in isotropic solvent. The syn/anti ratio of the frans-oxetane formed was reversed (Table 23). The effect was maximum with the bulkier substituents and was not observed on addition of a- and y-CD. The rationale is that deep inclusion in the P-CD... 

TABLE 23 Stereochemical Course of Photocycloaddition of 5-Sobstituted Adamantan-2-ones (5-X-ADs) with Fomaronitrile (1 20) in Aqueons Solution Containing CDs at Room Temperature... 

Many retinal and retinoic acid analogues have been synthesized. Many of the seven aromatic analogues of retinal (97)—(101), (103), and (104) and their geometrical isomers form stable complexes with cattle opsin, as does the allenic adamantyl retinal analogue (105) synthesized from adamantan-2-one. 5,6-Dihydro-, 7,8-dihydro, 9,10-dihydro-, 11,12-dihydro, and 9,10,11,12-tetra-hydro-retinals (106)—(110) have been synthesized from carbonyl intermediates, e.g. (Ill) prepared by selective reduction of the a,jS-unsaturation with... 

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