Methyl-bicyclo octane

Zu einer Losung von 0,6 g (16 mMol) Natriumboranat in 30 ml Methanol und 6 ml Wasser tropft man eine Losung von 0,7 g (2,3 mMol)4-Tosyloxy-2-oxo-l-methyl-bicyclo[2.2.2]octan in 90ml Methanol, riihrt 24 Stdn. bei 20°, gibt 300 ml ges. Calciumchlorid-Losung hinzu, schiittelt mit Petrolather aus, trocknet iiber Natriumsulfat und destilliert Ausbeute 0,3 g (95% d.Th.) Kpi, 108°. 

Unfortunately, the situation is even more complicated In bi- and tricyclic compounds the a-SCS may experience further alterations apparently produced by intramolecular strain. The usually large a-SCS(CH3) in 1-methyl-bicyclo[2.2.1]heptane (9) (93) has already been mentioned. The a-effects of other substituents (OH, OCH3, Cl, I, and COOH) in the same molecular system do not correlate with those in bridgehead-substituted bicyclo[2.2.2]octanes or adamantanes again this was attributed to internal strain (125). The a-SCS(F)... 

Direct bridgehead alkynylation of 1-iodoadamantane has been achieved by treatment with a variety of silver acetylides at reflux in IV-methylmorpholine.114 The methodology has been extended to the direct bridgehead substitution of methyl-bicyclo[2.2.2]octane and a carborate anion (Scheme 1.50).115... 

Under similar conditions, the 2-methylenebicyclo[2.2.1]heptane, or norcamphene (7) was conYerted to the isomer 6, through the intermediate formation of 5, whose maximum concentration in the mixtures is about 10%. This slow reaction is complicated by extensive hydrogen transfer and polymerization reactions (20), leading to saturated bicyclic hydrocarbons 2-methylbicyclo[2.2.1]heptane (12), bicyclo[3.2.1]- and [3.3.0]octanes (15 and 17). Isomerization of norcamphene (7) to hydrocarbons of the bicyclo[2.2.1]heptane series is also noticed at 250° in the vapor phase, but this is the main reaction at 140° in the liquid phase with the same catalyst. The main products are then 2-methyl-bicyclo[2.2.1]-2-heptene (8), l-methylbicydo[2.2.1]-2-heptene (10), and l-methyltricyclo[2.2.1.0]heptane 11 (13). The tricyclic isomer has been observed in the liquid-phase silica-alumina-catalyzed conversion of norbornene (21). 

Dehydration of 2-hydroxymethylbicyclo[2.2.2]octane at 380° in the presence of alumina also gives in good yields a mixture of the methyl-bicyclo[3.2.1]octenes containing 23, 22, and 21, besides two other products. One of these is the bicyclo[3.2.2]-2-nonene 15, 26), not yet found in the isomerization mixtures. 

Very strong acid catalysts are required to form the carbonium ions, but the conversion of these species, once formed, should lead to very similar reactions. Turova-Pollak and co-workers (33) found that aluminum chloride at 75° catalyzes the conversion of 2-methyl-bicyclo[2.2.1]hej)tane to bicyclo[3.2.1]octane, and the equilibrium mixture in the presencie of aluminum bromide was found by Schleyer and eo-workers (34) to be ... 

In the C9H16 series, the same authors found that under the same conditions 2-ethylbicyclo 2.2.1]-heptane gave 56% 2-methylbieyclo-[3.2.1Joctane, 8 /, 2-methylbicyelo[2.2.2]octane, and 24 ), x-methyl-bicyclo[3.3.0]octane. 

Reductive dehalogenation with tin hydrides can be carried out without interference of a number of functional groups. However, a C-C double bond in a 1,5 relationship to the intermediate cyelopropyl radical can function as a trap and result in formation of bicyclo[3.1.0]hexane derivatives. Thus, treatment of l,l-dibromo-2-(but-3-enyl)cyclopropane with tributyltin hydride afforded a 15 85 mixture of l-bromo-2-(but-3-enyl)cyclopropane (13) and 1-bromo-2-methyl-bicyclo[3.1.0]hexane (12). Under similar conditions l-bromo-2,8,8-trimethyltricyclo-[3.2.1.0 ]octan-3-one (15) was obtained in 6% yield from an isomeric mixture of 7,7-dibromo-4-isopropenyl-l-methylbicyclo[4.1.0]hept-2-one the main product, isolated in 86% yield, was an isomerie mixture of 7-bromo-4-isopropenyl-l-methylbicyclo[4.1.0]hept-2-one (14). ... 

Methyl-entfo-tricyclo[3.2.1.0 ]octane gave a 90 10 mixture of acetoxymercurio-substituted c (7o-2-methoxy-exo-2-methylbicyclo[3.2.1]octane 21 and exo-2-methoxy-eMr/o-2-methyl-bicyclo[3.2.1]octane 22 after mercuration and reduction. Likewise 2-methyl-enrto-tricyclo[3.2.1.0 ]oct-6-ene gave 23 and 24 in 82 11 ratio. ... 

The squalestatins, e.g. 6.28, also known as the zaragozic adds, have attracted considerable interest as inhibitors of squalene synthase and hence of cholesterol biosynthesis and lipid deposition in the circulatory system. They are also inhibitors of farnesyl protein transferase and thus they may have other potentially useful biological applications. They are formed by Phoma spedes and also by Setosphaeria khartoumensis. The squalestatins are characterized by a dioxabicyclo-octane core bearing three carboxyl groups and two polyketide chains, one of which is attached as an ester. The biosynthetic incorporation of succinic acid into part of the bicyclo-octane, together with its oxygenation pattern, indicate that it may be derived via oxaloacetic acid. Both the polyketide chains have several pendant methyl groups attached to them, which arise from methionine, whilst benzoic add ads as a starter unit for one of the chains. These complex structures are thus the summation of several biosynthetic pathways. 

The absorption for C-8 in both exo isomers is consistently upfield of the corresponding carbons in the endo isomers, while in the latter compounds, it is on the one hand C-4 and on the other C-7 that is affected by the methyl group. Care must be taken in making such analyses in systems where alternate diastereomers adopt different conformations. Thus, in the case of the 2-methyl -bicyclo[3.3.0]octanes, the shift of C-3 in the endo isomer is upfield compared to that of the exo diastereomer, presumably because the conformation of the former is such that C-3 and C-8 are sterically interacting, as depicted. In many of the cases with conformational freedom, analysis of carbon spectral data can provide not only configurational but conformational information as well. 

Hajos, Z. Parrish, D. R. (1974) Synthesis and conversion of 2-methyl-2-(3-oxobutyl)-l,3-cyclopentanedione to the isomeric racemic ketols of the [3.2.1] bicyclo octane and of the perhydroindan series, / Org. Chem., 39,1612-15. 

Reductions of cyclic 1,3-diketones being part of a medium sized ring are not effectively achieved as in the case of the five- or six-membered rings [198]. Reductions of the bridged 1,3-diketones 144 (Fig. 39) gave enantiomerically pure (i/ ,45,65)-6-hydroxy-l-methyl-bicyclo[2.2.2]octan-2-ones 145 [199,2(X)]. 

When formation of either the five- or six-membered ring was possible for N-chloroamine 37, only the five-membered ring was conducive under the Hofmann-Ldffler-Freytag reaction conditions, forming exclusively 6-ethyl-6-aza-bicyclo[3.2.1]-octane (38). No 2-ethyl-2-aza-bicyclo[2.2.2]-octane (39) was observed. On the other hand, 2-methyl-2-aza-bicyclo[2,2.2]octan-6-one (41) was installed by UV irradiation of a solution of A -chloroamine 40 in TFA. Ironically, when the ketone functionality on 40 was protected as its ethylene ketal group, the resultant steric interactions completely prohibited the classic Hofmann-Loffler-Freytag reaction. 

N H3c —COO H3C-COO It 0 K[BH4] 3-Hydroxy-8-methyl-trans-6,7-diacetoxy-8-aza-bicyclo[3.2.1]octan 84 3... 

Mehta et al. also studied the facial selectivities of 5,6-exo,eji o-disubstituted bicyclo[2.2.2]octan-2-ones 18 [75, 78]. These systems are related to the 2,3-exo,ex( -disubstituted 7-norbomanones 14, but differ in the direction of the carbonyl n face. Hydride reduction of 5,6-exo,ex( -disubstituted bicyclo[2.2.2] octan-2-ones (18) with NaBH and DIBAL-H and methylation with MeLi were smdied [75, 78],... 

Scheme 13.17 depicts a synthesis based on enantioselective reduction of bicyclo[2.2.2]octane-2,6-dione by Baker s yeast.21 This is an example of desym-metrization (see Part A, Topic 2.2). The unreduced carbonyl group was converted to an alkene by the Shapiro reaction. The alcohol was then reoxidized to a ketone. The enantiomerically pure intermediate was converted to the lactone by Baeyer-Villiger oxidation and an allylic rearrangement. The methyl group was introduced stereoselec-tively from the exo face of the bicyclic lactone by an enolate alkylation in Step C-l. 

Twofold Michael additions have been utilized by the groups of Spitzner [2] and Hagiwara [3] to construct substituted bicyclo[2.2.2]octane frameworks. In Hagiwara s approach towards valeriananoid A (2-6) [4], treatment of trimethylsily-enol ether 2-2, prepared from the corresponding oxophorone 2-1, and methyl acrylate (2-3) with diethylaluminum chloride at room temperature (r.t.) afforded the bicyclic compound 2-4 (Scheme 2.2). Its subsequent acetalization allowed the selective protection of the less-hindered ketone moiety to provide 2-5, which could be further transformed into valeriananoid A (2-6). 

Figure 21. Absorption spectra of (a) S-D dyads (3a 3b = 1 1), (b) 1-methyl-4-(2-naphthyl)bicyclo[2.2.2]octane (2-S), and (c) butylferrocene (Bu-Fc) in cyclohexane.

The results obtained in combination with the data on the transformations of cations 9-11, led to the conclusion that 1,2-shifts of methyl groups occur readily in carbocations having a pentalene fragment. On the basis of the data obtained for rearrangements of such carbocations, an alternative mechanism has been proposed (52) for the rearrangement of structurally related carbocation 16 having a bicyclo[3.3.0]octane skeleton described in (33) (Scheme 12). 

The pKR+ value for the parent tri(l-azulenyl)methyl cation (2a+) is 11.3. Hydrocarbon-based carbocations, which comprise only of carbon and hydrogen, are generally very reactive species. Some extremely stable hydrocarbon carbocations, which exist even under basic conditions, were reported in the literature (5). However, most of these examples are cyclic cations, such as cyclopropenylium or tropylium ions (Figure 8). The tropylium ion 8+ annelated to three bicyclo[2.2.2]octane units is one of the most stable hydrocarbon-based carbocation ever reported (9). 

Nucleophilic addition of ester-derived enolate to the bicyclo[3.3.0]octan-2-one system of diacetone glucos-3-ulose usually occurs at the convex jS-face of the carbonyl (as for other nucleophiles), except for senecioate-derived enolate (from 3-methyl cro-tonate) for which a-attack in diethylether solvent is in contrast to the jS-face attack in THF the reason for this anomalous behaviour is not clear. 

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