Decalin system

The Birch reductions of C C double bonds with alkali metals in liquid ammonia or amines obey other rules than do the catalytic hydrogenations (D. Caine, 1976). In these reactions regio- and stereoselectivities are mainly determined by the stabilities of the intermediate carbanions. If one reduces, for example, the a, -unsaturated decalone below with lithium, a dianion is formed, whereof three different conformations (A), (B), and (C) are conceivable. Conformation (A) is the most stable, because repulsion disfavors the cis-decalin system (B) and in (C) the conjugation of the dianion is interrupted. Thus, protonation yields the trans-decalone system (G. Stork, 1964B). 

Various bicyclic and polycyclic compounds are produced by intramolecular reactions] 127]. In the syntheses of the decalin systems 157 [38] and 158 [128], cis ring Junctions are selectively generated. In the formation of 158, allyhc silyl ether remains intact. A bridged bicyclo[3.3. l]nonane ring 159 was constructed... 

The same regioselective and stereospecific reactions are observed in decalin systems. The 3/3-formate 605 is converted into the a-oriented (j-allylpalladium complex 606, and the hydride transfer generates the fra .s-decalin 607, while the cis junction in 610 is generated from the 3tt-formate 608 by attack of the hydride from the /3-side (609). An active catalyst for the reaction is prepared by mixing Pd(OAc)2 and BU3P in a 1 I ratio with this catalyst the reaction proceeds at room temperature. The reaction proceeded in boiling dioxane when a catalyst prepared from Pd(OAc)2 and BujP in a 1 4 ratio was used[390]. 

The /rans-fiised decalin system is conformationally rigid, and the stereochemistry of the product indicates that the initial addition of the trichloromethyl radical is from the axial direction. This would be expected on stereoelectronic grounds, because the radical should initially interact with the n orbital. The axial trichloromethyl group then shields the adjacent radical position enough to direct the bromine abstraction in the trans sense. 

Similarly, efficient tetracyclization (MeAlCl2-promoted) of the bis-allylic silane/ bis-epoxide 97 constitutes the key step in the synthesis of (+)-a-onocerin. In this case, because of the presence of the bis-allylic silane group, a double bis-annula-tion occurs, with the formation of the ethylene-bridge linked bis-decalin system present in the target compound (Scheme 8.26) [46],... 

Entry 6 shows a stereoselective formation of a highly substituted frans-decalin system. The reaction in Entry 7 establishes a taxanelike structure. The stereochemistry is consistent with a TS in which both the carbonyl oxygen and the methoxy group are coordinated to aluminum. 

Partial structures I and II thus obtained were connected through the carbonyl group by the strong HMBC correlations of H-7 (8 4.05ppm) and H-9 (8 3.18ppm) to C-8 carbonyl carbon (8 208.5 ppm). Thus, the total planar structure of 46, including the partial relative stereostructure of the decalin system, was elucidated as shown in Figure 4. 

Starting from quinic acid, a highly substituted, cis-afi unsaturated nitrile oxide has been synthesized and used in a 1,3-dipolar cycloaddition, to afford a precursor of the cis -decalin system of branimycin (468). 

All the new chiral centers are controlled by the rigid structure of the dithia-decalin system. Taking the NaBH4 reduction of 14 as an example, the orientation of the fused rings forces the H- to attack from the Sl -prochiral face of the carbonyl group (Fig. 7-1). 

Alternatively, the use of an auxiliary with an (f )-stereochemistry at the phenyl-2-(phenylsulfanyl)ethyl moiety will lead to the formation of a 1,2-traro-glycoside because in this case the trans-decalin system will exert unfavourable steric interactions. The proposed mechanism has been supported by computational studies.39... 

Therefore, nine steps or synthetic operations are necessary in the conessine synthesis for isomerising the cir-B/C decalin system to trans-hIC, a transformation that in the cortisone synthesis is accomplished without any extra step, since it takes place spontaneously in the oxidation step, which, in turn, is necessary to introduce the second angular methyl group and build up ring D of cortisone in a stereoselective manner. Better correlation amongst different synthetic operations would be difficult to find in more recent synthesis of similar complexity and magnitude than that of Sarett. 

Another example, which takes place in weakly basic conditions, is provided by the key step of the synthesis of aromadendrene (111 accomplished by Biichi and coworkers [4], in which a cw-decalin system (9) rearranges to a hydroazulene system (10) through a process induced by activated AI2O3 (Scheme 7.3). 

The opening of the epoxide in the cij-decalin 24 by acetic acid leads exclusively to the hydroxyacetate 25 (through a kinetically controlled rrani-diaxial opening) rather than to the wanted diastereomer 26 (c/ the stereochemistry of the "southern" part of reserpine). To obtain the correct diastereomer the epoxy-lactone 22 is first formed (Scheme 8.6). Thus the conformation of the cij-decalin system, and therefore that of the substituents, is reversed. The kinetic tran -diaxial opening of the epoxide occurs in a regio- and stereoselective manner to afford compound 28 in which the substituents have the correct position and configuration (a-OH, P-OAc),... 

HP-6 Reference to aromatic systems stability, orientation rules and their relationship with more or less unsaturated cyclohexane rings and decalin systems. 

The 1,2-carbonyl transposition takes place through the enJo-epoxide 18 easily prepared through the tosylhydrazone 16, followed by regioselective cleavage to the less substituted double bond (17) with 2 equivalents of methyllithium [4] and epoxidation with MCPBA in chloroform from the more accesible convex face of the decalin system. 

Notice that although the A -enol is favoured over the A -enol in c -decalin systems [8], the resulting product from the corresponding Mannich condensation would lead to a highly congested compound with two 1,3-diaxial interactions instead of only one 1,3-diaxial interaction in luciduline. 

In the trans-decalin systems 329T, the substituents occupy well-defined axial or equatorial positions, whereas in the mobile ds-decalin system 329C, the substituents occupy either the equatorial or the axial orientation and, if the framework equilibrium is unbiased (as in decalin itself), the preferred conformation will be that with the equatorial substituent. Although this is mainly true for the 1,3-hetero analogs as well, there are also other factors (discussed later) to be taken into account. 

Among hydrocarbons, the differences between the experimental and calculated values of r must be almost entirely a steric effect polar effects are small and must be transmitted through two oxygen atoms. The largest authentic steric effect known to us is that in the Tetralin-Decalin system, where the rarb product is 0.5. This product means that if we take any steric effects in the reactions of tetralylperoxy radicals with Tetralin or Decalin as base points, reaction of decalylperoxy with Decalin is retarded sterically by 50% more than it is retarded with Tetralin. This result is plausible when we consider the structures of Decalin and the derived radical. 

Synthesis of a m-decalin system by the asymmetric cyclization[38] has been carried out with high enantioselectivity[142,143,147,148], Using BINAP as a chiral ligand, 91% ee was achieved in the asymmetric cyclization of 177 to give 178. In order to achieve an efficient asymmetric cyclization, selection of the reaction conditions is crucial, and sometimes added Ag salts play an important role[148], A catalytic asymmetric cyclization of 179 to prepare the key intermediate enone 180 for vernolepin synthesis has been carried out[149]. Highly efficient asymmetric cyclization of 181 to give the tetralin system 182 has been applied to the synthesis of (-)-eptazocine (183)[150], Hydrindans are synthesized in 86% ee[151]. 

Other examples in which the decalin system has been modified have been described. The epoxide (39) (PF1052) has been reported as a metabolite from an isolate of a Phoma sp. It showed good activity against Staphylococcus aureus (MIC 3.13 pg/ml), Streptococcus parvulus (0.78 pg/ml) and Clostridium perfringens (0.39 (ig/ml) [73]. 

Occidentalol (628), a eudesmane-type sesquiterpene isolated from the wood of Eastern white cedar, was synthesized from a as-fused decalin system (627) prepared by cycloaddition of the a-pyrone (625) with 4-methyl-3-cyclohexenone (626 Scheme 140) (72TL4651). Derivatives of 2-pyrone have also been employed in syntheses of colchicine (629 Scheme 141) (59AG637) and barrelene (630 Scheme 142) (69JA2330). 

The acetonation under kinetically controlled conditions is also useful for the protection of vicinal rra/u-diols, which are quite reluctant to cyclization into five-membered rings. Although use of 2-methoxypropene has been successful in this objective [61,66], one should recommend the recently discovered uses of reagents that minimized the ring strain by obtaining six-membered rings from vicinal mmr-dials, which are protected (Scheme 10) as 1,4-dioxanes (dispiroacetals, rranr-decalinic system) stabilized by an anomeric effect... 

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