Chiral tetralins

A well-studied group of organogelators are derived from anthracene and anthraquinone (4,5) [13], or steroids (6) [14], and include also compounds which contain both groups linked via a spacer (7,8) [15,16], Other organogelators of this type are an azobenzene-steroid derivatives (9) [17] and a chiral tetraline derivative (10) [18]. Aggregation of these compounds is based upon n-n stacking and solvophobic effects. Figure 2 presents some examples. 

Fig. 7-6). Two unichiral amides which have been known capable of this reaction are 1-phenylethylamine [15] and l-(l-naphthyl)ethylamine [16]. Marfey s reagent [N-a-(2,4-dinitro-5-fluorophenyl)-L-alaninamide] was introduced as a reagent to deriva-tize amino acids with cyclopentane, tetrahydroisoquinoline or tetraline structures [17]. Simple chiral alcohols such as 2-octanol can also be used to derivatize acids such as 2-chloro-3-phenylmethoxypropionic acid [18]. 

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]. 

The highly efficient asymmetric cyclization of 97 using (i )-BINAP as a chiral ligand based on the differentiation of enantiotopic faces gave the tetralin system 98 with 93% ee and has been applied to the synthesis of (—)-eptazocine (99) [45]. 

A synthetic route to asymmetric tetralins applies the cyclization of chiral acrylates 28 or fumarates 38 to 2-quinodimethanes, which must be generated in situ. Different procedures lead to a-hydroxy 2-quinodimethanes 49 and 56, for instance the irradiation of 2-methylbenzalde-hyde (48)10 or thermolysis of the benzocyclobutene 53 or the cyclic sulfone 541... 

Inverse demand cycloaddition of isoquinolinium salt 1 to chiral enol ethers, acetals and ortho esters 2 gives diastereomeric tetralins 3 and 4 with the diastereoselectivity depending on the nature of the dienophile and on the chiral auxiliary1. The primary tricyclic adduct solvolyzes to the tetralinaldehyde acetal in acidified alcohol. 

Alkylation. Acetals of enals serve as alkylating agents for t-butyl (3-keto esters using a Pd complex of BINAP. With a cationic Pd complex of (R)-BINAP intramolecular addition of arylboronic acid moiety to a sidechain ketone leads to chiral, tertiary henzylic alcohols. Heck reaction. Cyclization with desymmetrization is shown to proceed in excellent yields and ee by the formation of tetralin derivatives. ... 

Thermal decomposition of l,4-dihydro-2,3-benzoxathiin 3-oxides generates o-xylylenes which can be trapped by methyl 2-acetamidoacrylate yielding tetralin-based a-amino acids <04S558>. A phosphazene base [EtN=P(NMe2)2(N=P(NMe)2)3)] is used to generate the ylide from chiral oxathiane 74 in a two-step asymmetric synthesis of aziridines from tosylimines <04JOC1409>. 

The calamenene skeleton contains only two asymmetric carbon atoms 1,4-disposed on a tetralin system. Until recently, the synthesis of this skeleton had only been achieved starting from chiral pool agents with the two asymmetric carbon atoms of interest of predetermined configuration (71,72). Recent developments in synthetic methodology now allow the elaboration of the 1,4-P-aiw-or 1,4-ci j- disubstituted system starting from 5-methoxytetralone or its equivalent (73-75). 

A more general approach concentrates on the chiral modification of the carbene ligand. Some examples based on a chiral carbene carbon side chain are depicted in Figure 4. [68] The reaction of alkoxy- and amino(cyclohexenyl)carbene complexes with 1 -pentyne afforded diastereomeric tetralin complexes in moderate yields. [69] The sense of stereoselection was found to depend on the substitution pattern of the cyclohexenyl substituent. Whereas 5-methyltetralin derivatives were obtained in low preference for the syn complex, a higher preference for the anti diastereomer was observed synthesizing the 8-methyltetralin complexes 50 (Scheme 27). [69]... 

Reactions of chiral 2-quinodimethanes witii alkyl acrylates, fumarates or maleic anhydride lead to tetralines. Moderate selectivities (d.r. 83 17) were obtained. 

Isoquinolinium salts represent 2-aza-1,3-butadienes activated by A-arylation. Highly stereoselective cycloadditions with chiral enolethers have been reported leading to enantiomerically pure functionalized tetralines in high yields. 

The amidation of saturated C—H bonds can be effectively catalyzed by ruthenium or manganese complexes. Unfunctionalized hydrocarbons, such as adamantane, cyclohexene, ethylbenzene, cumene, indane, tetralin, diphenylmethane and others, are selectively amidated with PhINTs in the presence of ruthenium or manganese porphyrins or the ruthenium cyclic amine complexes to afford N-substituted sulfonamides in 80-93% yields with high selectivity [807]. The enantioselective amidation of a C—H bond can be catalyzed by chiral (salen)manganese(III) complexes (e.g., 660) [808], or by chiral ruthenium(II) and manganese(III) porphyrins (Scheme 3.264) [809]. 

The variety of uses of (-)-isopropylephedrine as a chiral auxiliary in enantiose- Another important tetra-lective protonation was demonstrated by Charles Fehr, not only for damascene lin-musk scent is tonalide. Its but also for tetralin-musk-scented compounds (e.g. Vulcanolide ). Deprotonation of 2,2,4,5-tetramethylhex-4-en-3-one with LDA gives the dienolate in an ( /Z)-ratio of 1 9. This can be protonated very selectively with iso-... 

Multienzyme cascade synthesis combining ene-reductases with alcohol dehydrogenases, (a) Synthesis of optically pure y-butyrolactones (the building block is circled) and (b) optically pure primary or secondary tetralin orchroman derivatives, (c) Three-enzyme system for the generation of a valuable chiral building block. 

---