Decalin, cyclization

Thermolysis of the 3-acyl-3/f-azepine 32 in Decalin at 250°C also gives the phenacylpyridine but in much reduced yield (6%). In a similar manner, 4-chloro-yV,/V-diethyl-3-phenacylpyridin-2-amine (53 % bp 160 C/0.18 Torr) is produced by the photolysis or thermolysis of 3-benzoyl-5-chloro-Ar,Ar-diethyl-3/f-azepin-2-amine.246 However, if the 3ff-azepine bears a secondary amine residue at the 2-position, e.g. 36, then photolysis or thermolysis yields a pyrrolo[2,3-/>]pyridine by intramolecular cyclization of the 3-phenacylpyridin-2-amine intermediate. 

For most dienes, 7r-bonds adjacent to quaternary centers do not undergo insertion reactions. One notable exception is 1,5-diene (75) (Scheme 17) [44], For this substrate, the observed selectivity is inconsistent with a chair-like (in this case a trans decalin-like) transition structure (76 top) leading to the insertion product, which is typically seen in diene cyclizations with 70 [36]. 

Intramolecular Diels-Alder cyclizations of (E)- -nitro-1,7.9-decatrienes under thermal conditions and Lewis acid conditions lead to the formation of decalin ring systems with excellent endo selectivity (Eq. 8.21). This strategy is used for preparing of the AB ring system of norzoanthamine.33... 

BEP819195 75GEP2343462), and decaline (69T4649) have been used. Dowtherm A (b.p. 260°C) is used most widely this is a eutectic mixture of diphenyl ether (73.5%) and biphenyl (26.5%). It is superior to pure diphenyl ether (m.p. 26-27°C) because of its lower freezing point (12°C) (e.g., 46JA1204, 46JA1264). The cyclization can be carried out above 300°C when dibenzylbenzene is used as solvent. 

Dimethyl methyithio(phenylamino)methylenemalonate was cyclized in boiling decalin for 2 hr to afford methyl 2-methylthio-4-hydroxyquinoline-3-carboxylate in 70% yield (69T4649). 

Fig. 29 Formation of isomeric decalins [71 ]—[73] by cyclization of a terpenoid alcohol catalysed by antibody HA5-19A4 raised to hapten [82]. The transition state [83a] has the leaving group in the equatorial position, as favoured by the Stork-Eschenmoser...

While cyclopentanes have also been produced by antibody-catalysed cyclization (Appendix entry 15.2) (Li et al., 1996), much the most striking example of cationic cyclization by antibodies is the formation of the decalins [79], [80] and [81] (Fig. 29). The rra/w-decalin epoxide [82] (tu2 100 h at 37°C) was employed as a mixture of two enantiomeric pairs of diastereoisomers as a TSA to raise antibodies, among which HA5-19A4 emerged as the best catalyst for cyclization of substrate [83] (Appendix entry 15.4) (Hasserodt et al., 1997). 

Corey s retrosynthetic concept (Scheme 9) is based on two key transformations a cationic cyclization and an intramolecular Diels-Alder (IMDA) reaction. Thus, cationic cychzation of diene 50 would give a precursor 49 for epf-pseudo-pteroxazole (48), which could be converted into 49 via nitration and oxazole formation. Compound 50 would be obtained by deamination of compound 51 and subsequent Wittig chain elongation. A stereocontroUed IMDA reaction of quinone imide 52 would dehver the decaline core of 51. IMDA precursor 52 should be accessible by amide couphng of diene acid 54 and aminophenol 53 followed by oxidative generation of the quinone imide 52 [28]. 

The thermal cyclization of 3-(l,3-butadienyl)indoles 692 in refluxing cis-decalin afforded the carbazoles 698. Selective hydrolysis of the 3-carbonate ester, methylation of the corresponding 3-hydroxycarbazoles 699 with methyl iodide in the presence of... 

These cyclizations are usually highly stereoselective, with the stereochemical outcome being predictable on the basis of reactant conformation.14 The stereochemistry of cychzation products in the decalin family can be predicted by assuming that cyclizations will occur through conformations which resemble chair cyclohexane rings. The stereochemistry at ring junctures is that expected for anti attack at the participating double bonds ... 

Hydrolysis of the enamine 14 furnishes citronellal (15) in high optical purity (ca. 99% ee) which gives 17 via ene cyclization with zinc bromide as catalyst. The diastereoselectivity of this step is the result of simple diastereoselection in a trans-decalin-like transition state 16. Catalytic hydrogenation converts the olefin 17 into (—)-menthol (18). Despite its elegance this novel route has not been able to replace the older resolution-based procedure described earlier in this section. 

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]. 

A report that JV-(3-halopropyl)benzylamines cyclize to tetrahydro-2-benzazepines in hot decalin in the presence of an aluminum chloride catalyst is incorrect 4-methyltetra-hydroisoquinolines are the major products (>60%) along with only minor amounts (<20%) of the seven-membered heterocycle (80JOC2000). 

Other tetraazapentalenes have been produced by photochemical or thermal decomposition of azidophenyl-l - and -2//-benzotri-azoles.339-341 Hall, Stephanie, and Nordstrom341 found that decomposition of the azide 259 in decalin at 170° led to a mixture of 260 and 261 in the ratio 1 9. The preference for cyclization to the position para to the methyl group to give 261 is consistent with the known electrophilic character of the intermediate nitrene. 

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... 

J. C. Lopez, A. M. Gomez, and B. Fraser-Reid, Silicon-tethered radical cyclization and intramolecular Diels-Alder strategies are combined to provide a ready route to highly functionalized decalins, J. Chem. Soc. Chem. Comtmm. p. 762 (1993). 

Intermolecular acylation of 3,4-dimethoxyphenylacetic acid occurs in polyphosphoric acid, leading to 2-(3,4-dimethoxyphenylacetyl)-4,5-dimethoxyphenylacetic acid (622). Cyclization to the isochromanone takes place when the keto acid is heated in decalin (Scheme 240) (72JHC853). 

Cyclization to five-membered rings forms the alkylindans and indenes cyclization to six-membered rings gives tetralins and naphthalenes. Tetralins and decalins, however, were not observed in any of the experiments, because of unfavorable equilibrium. For example, less than 0.02-0.1% tetralin and less than 0.001% decalins would be expected if they were in equilibrium with the naphthalene formed in the n-butylbenzene experiments. [Equilibrium conversions calculated from the data of Egan (15), Allam and Vlugter (16), and Frye and Weitkamp (17)]... 

The usefulness of this cis-decalin synthesis was demonstrated by an enantioselective synthesis of the sesquiterpene (+)-vemolepin 6.4 (Scheme 8G.6). Thus, Heck cyclization of the... 

Asymmetric cyclization using chiral ligands offers powerful synthetic methods for the preparation of optically active compounds [39]. After early attempts [40,41], satisfactory optical yields have been obtained in a number of cases. Synthesis of the optically active cA-decalin system [42] was carried out with high enantioselectivity based on the differentiation of enantiotopic C=C double bonds [43]. The cyclization of the triflate 93 gave the cA-decalin 94 with 95% ee in 78% yield using (i )-BINAP. A mixture of 1,2-dichloroethane and f-BuOH is the best solvent, and the asymmetric synthesis of vemolepin (96) via Danishefsky s key intermediate 95 has been achieved [44]. 

Optically active cis-decalins can be obtained from substrates such as 4 by a Heck-type reaction with PdCl2/(R)-l (1 1) as the catalyst.8 Addition of various silver salts improves the yield and enantioselectivity. For cyclization of 4 to 5, the highest enantioselectivity was observed by use of Ag3P04 and CaC03 (2 equiv. of each) with 1 -methyl-2-pyrrolidinone (NMP) as solvent (60°). 

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). 

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