Decalin derivatives

Scheme 29 Tandem benzannulation-Mitsunobu reaction of a chiral decalin-derived carbene complex...

Retrosynthesic step II => III is attractive, because it suggests a decalin derivative as a key intermediate. Methods for preparing structures of this type have been well developed, because they are useful intermediates in the synthesis of other terpenes and also steroids. 

The mechanistic and synthetic groundwork has been unequivocally established for the consecutive cycloreversion transannular ene reaction sequence, from which /ra/w-decalin derivatives with a hydroxyl group at the ring junction are produced.146,147 As an example, the thermally induced cycloreversion of the ester 43 at 200°C affords 45 in an astonishing 96% yield.146 Presumably the initial cycloreversion product 44 is converted by a transannular ene reaction to generate the decalin 45.146 However, not all the cycloreversion reactions proceed to give a single product as predicted, as can be shown by the examples collected in Table 7. In fact, closer inspection of work already reported has shown that complex product mixtures are usually obtained from cyclobutane cycloreversion reactions.143,148 152... 

As can be seen from Table VI, secondary aliphatic, allylic, and benzylic alcohols are all quantitatively converted into the corresponding carbonyl derivatives. It is interesting to note that no epimeriza-tion of menthone takes place under these conditions (Entry 3). Furthermore, rather hindered decaline derivatives (Entry 5) are also smoothly oxidized. 

The palladium-catalyzed arylation and alkenylation of olefins, which were first discovered in the 1970 s by Heck (7,2) and Mizoroki (3) and have been often called the "Heck reaction", are versatile synthetic means for making a carbon-carbon bond. These reactions have been extensively used for organic synthesis during the past two decades (4-7). However, no reports on the "asymmetric Heck reaction" have been appeared until very recently. Shibasaki reported an asymmetric intramolecular cyclization of alkenyl iodides to give c/j-decalin derivatives of 80-91% ee (8-10). Overman reported an intramolecular cyclization of alkenyl triflate, giving a chiral quaternary carbon center of 45% ee (77). We report herein the first example of intermolecular asymmetric Heck-type arylation of cyclic olefins catalyzed by (7 )-BINAP-coordinated palladium complexes (Scheme 1) (12,13). 

Using methylene-triphenylphosphorane 205, in many cases carbonyl functions have been converted into exomethylene groups in cyclic terpene chemistry. This technique was used, among others in the preparation of (+)-steviol methyl ether 244), dihydro-5,6-norcaryophyllene 245), ( )-nootkatone 246 (-)-phyllodadene 247), and (+)-e-cadinene 248). In the synthesis of the latter the trans-decalin derivative 462 was formed from the cis-decalone 461 the epimerization of which proceeded via the enol form during the methylenation 248 (Scheme 80). 

The famous ligand BINAP controls an intramolecular Heck reaction to give decalin derivative... 

A Lewis acid-mediated two-fold asymmetric Michael addition allows access to c( s-decalin derivatives. The reaction of the trimethylsilylenol ether of acety Icyclohexene with phenylmenthyl acrylate in the presence of Diethylaluminum Chloride (eq 7) yields the decalone in 64% yield (70% de). This has been shown not to be a Diels-Alder reaction. If the reaction is worked-up early, the initial Michael adduct can be isolated. ... 

Draw three-dimensional structures for each decalin derivative. 

The famous ligand BINAP controls an intramolecular Heck reaction to give decalin derivatives with good enantiomeric excess. BINAP is the optically pure phosphine built into the palladium catalyst. The presence of silver ions accelerates the reaction as well as preventing double bond isomerization in the original substrate. This time the chiral ligand selects which double bond is to take part in the reaction. The vinyl palladium species is tethered to the alkene and can reach only the same face. The faces of the alkenes are diastereotopic but the two alkenes are enantiotopic and you must know your right from your left to choose one rather than the other. 

The most potent members of all of these series of decalin-derived molecules have anti-planar Tg stereochemistry. In the series of cyclohexane-derived compounds (231), the XRy2Ii)-trans compound was an extremely weak muscarinic and the ( )-cis-isomer was completely inert (275). Casy (256) suggested that an energetically unfavored trans-diaxial conformer (antiplanar Tg) for structure (231) may be the pharmacologically active form of the molecule. However, introduction of at-bu-tyl group into the cyclohexane system to sta-... 

The aldehyde alkene substrate 101 [Eq. (24)] was found to cyclize to an epimeric mixture of cis-decalin derivatives 102 and 103. Similarly, acyclic substrate... 

Alcohol dehydrogenase from pig liver (/ e-face selective), from Mucor javanicus (Si-face selective), and, especially, from horse liver (/fe-face selective) can be used for the reduction of cyclic ketones. The horse liver enzyme is very well characterized and models for the prediction of the stereochemical course of the reaction have been developed278,279. When subjected to horse liver alcohol dehydrogenase (HLADH) reduction, the following decalin derivatives yield products with >98% ee279,280. e.g. ... 

Alkene positional isomerism is a problem that arises from time to time. It is conceptually related to regiochemistry and is presented here. Careful synthetic planning is usually required to solve this problem, as illustrated by the Burk-Soffer synthesis of e-cadinene (53) and V2-cadinene (54). 9 Conversion of 52 first to the ketone, then to the tertiary alcohol, and finally to the tertiary chloride allows E2 elimination to give 53. Conversely, Wittig olefination (sec. 8.8.A) of the ketone gave the exo methylene derivative, 54. It is important to note that formation of the C2-C3 C=C unit is favored for trans decalin derivatives over the C3-C4 unit. 

In 2001, Marko et al. reported a neutral variant of their Cu Cl(phen)-DBADH2-base system 91). A catalytic amount of base was used, i.e., 5mol% potassium er -butoxide, which was advantageous for pH-sensitive substrates and products. The order of addition of the different reactants turned out to be crucial for the reactivity. The best catalytic procedure was obtained when the base was added to the [Cu Cl(Phen)]2 complex in the presence of the alcohol, followed by the addition of DEAD. A number of sensitive and/or sterically hindered alcohols were oxidized at 80°C using this optimized protocol and the results are shown in Table IX 91). (lS,2S,5i )-Neomenthol was converted to menthone without any epimerization to isomenthone. A rather hindered decaline derivative could be smoothly oxidized as well as... 

Sato, Y., Sodeoka, M. and Shibasaki, M. (1990) On the role of silver salts in asymmetric Heck-type reaction. A greatly imrpoved catatytic asymmetric synthesis of cis-decalin derivatives. 

Sato, Y., Watanabe, S. and Shibasaki, M. (1992) Further studies on a catalytic asymmetric synthesis of decalin derivatives. Tetrahedron Lett., 35, 2589-92. 

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