Chiral 1,2-dihydronaphthalenes

Chiral catalysts, asymmetric metal-catalyzed suHoxidations, 478-85 Chiral 1,2-dihydronaphthalenes, photooxygenation, 265-6 Chiral dioxetanes, stereoselective synthesis, 1173-8... 

Linker, T., Rebien, E, and Toth, G., Highly diastereoselective photooxygenation of chiral 1,2-dihydronaphthalenes evidence for a common intermediate in the ene reaction and the [4 -i- 2] cycloaddition, J. Chem. Soc., Chem. Commun., 2585, 1996. 

MEYERS Asymmetric synthesis Chiral oxaioles in asymmetric synthesis of cartxixylic acids, aldehydes, chiral dihydronaphthalenes. 

This approach is based on the chiral dihydronaphthalene motif, represented by compound (f )-8. Generally, this motif is found in a number of biologically active molecules and therefore it is a chemically privileged structure in the sense of being a starting point for the identification of a lead compound for evaluation [30]. 

Chiral oxazolines developed by Albert I. Meyers and coworkers have been employed as activating groups and/or chiral auxiliaries in nucleophilic addition and substitution reactions that lead to the asymmetric construction of carbon-carbon bonds. For example, metalation of chiral oxazoline 1 followed by alkylation and hydrolysis affords enantioenriched carboxylic acid 2. Enantioenriched dihydronaphthalenes are produced via addition of alkyllithium reagents to 1-naphthyloxazoline 3 followed by alkylation of the resulting anion with an alkyl halide to give 4, which is subjected to reductive cleavage of the oxazoline moiety to yield aldehyde 5. Chiral oxazolines have also found numerous applications as ligands in asymmetric catalysis these applications have been recently reviewed, and are not discussed in this chapter. ... 

The first use of chiral oxazolines as activating groups for nucleophilic additions to arenes was described by Meyers in 1984. " Reaction of naphthyloxazoline 3 with phenyllithium followed by alkylation of the resulting anion with iodomethane afforded dihydronaphthalene 10 in 99% yield as an 83 17 mixture of separable diastereomers. Reductive cleavage of 10 by sequential treatment with methyl fluorosulfonate, NaBKi, and aqueous oxalic acid afforded the corresponding enantiopure aldehyde 11 in 88% yield. 

Asymmetric epoxidation of olefins with ruthenium catalysts based either on chiral porphyrins or on pyridine-2,6-bisoxazoline (pybox) ligands has been reported (Scheme 6.21). Berkessel et al. reported that catalysts 27 and 28 were efficient catalysts for the enantioselective epoxidation of aryl-substituted olefins (Table 6.10) [139]. Enantioselectivities of up to 83% were obtained in the epoxidation of 1,2-dihydronaphthalene with catalyst 28 and 2,6-DCPNO. Simple olefins such as oct-l-ene reacted poorly and gave epoxides with low enantioselectivity. The use of pybox ligands in ruthenium-catalyzed asymmetric epoxidations was first reported by Nishiyama et al., who used catalyst 30 in combination with iodosyl benzene, bisacetoxyiodo benzene [PhI(OAc)2], or TBHP for the oxidation of trons-stilbene [140], In their best result, with PhI(OAc)2 as oxidant, they obtained trons-stilbene oxide in 80% yield and with 63% ee. More recently, Beller and coworkers have reexamined this catalytic system, finding that asymmetric epoxidations could be perfonned with ruthenium catalysts 29 and 30 and 30% aqueous hydrogen peroxide (Table 6.11) [141]. Development of the pybox ligand provided ruthenium complex 31, which turned out to be the most efficient catalyst for asymmetric... 

The reaction of butyllithium with 1-naphthaldehyde cyclohexylimine in the presence of (/C )-l,2-diphenylethane-1,2-diol dimethyl ether in toluene at —78 °C, followed by treatment with acetate buffer, gave 2-butyl-1,2-dihydronaphthalene-l-carbaldehyde, which was then reduced with sodium borohydride in methanol to afford (1 R,2.S)-2-butyl-1 -hydroxymcthyl-1,2-dihydronaphthalene in 80% overall yield with 91 % ee83. Similarly, the enantioselective conjugate addition of organolithium reagents to several a,/J-unsaturated aldimines took place in the presence of C2-symmetric chiral diethers, such as (/, / )-1,2-butanediol dimethyl ether and (/, / )- ,2-diphenylethane-1,2-diol dimethyl ether. 

The photooxygenation of chiral l,2-dihydronaphthalene-2-carboxylic acids leads to a mixture of the diendoperoxide (37) and hydroperoxide (38) arising from a double [4+2] cycloaddition and an ene reaction, respectively <96CC2585>. 

Chemical catalysts for transfer hydrogenation have been known for many decades [2e]. The most commonly used are heterogeneous catalysts such as Pd/C, or Raney Ni, which are able to mediate for example the reduction of alkenes by dehydrogenation of an alkane present in high concentration. Cyclohexene, cyclo-hexadiene and dihydronaphthalene are commonly used as hydrogen donors since the byproducts are aromatic and therefore more difficult to reduce. The heterogeneous reaction is useful for simple non-chiral reductions, but attempts at the enantioselective reaction have failed because the mechanism seems to occur via a radical (two-proton and two-electron) mechanism that makes it unsuitable for enantioselective reactions [2 c]. 

In 1998, Page and coworkers reported a series of dihydroisoquinoline-related iminium salts which can be readily synthesized in three steps from a chiral amine (Scheme 14) [140-143], Among the catalysts tested for asymmetric epoxidation, iminium salts 74 were found to be efficient catalysts (Fig. 24, Table 7, entries 2, 4-6, 17-19). Iminium salts 74a can epoxidize 4-phenyl-1,2-dihydronaphthalene in up to 63% ee (Table 7, entry 17). 

The methodology was extended to an asymmetric introduction of snbstitnents to a naphthalene ring. When chiral naphthyloxazolines 13 were used as substrates, di- or trisubstituted dihydronaphthalenes 15 were obtained in high diastereomeric ratio (dr) after the treatment of intermediate azaenolate 14 with an electrophile (equation 7) °. Analogous reactions with a chiral naphthaldehyde imine were also reported . 

As is the case with non-chiral epoxidations model systems are much used, and styrene (and substituted styrenes), stilbenes and 1,2-dihydronaphthalene are the preferred models. 

The effect of structural variation and the use of different caboxylate salts as cocatalysts was investigated by Pietikainen . The epoxidation reactions were performed with the chiral Mn(III)-salen complexes 173 depicted in Scheme 93 using H2O2 or urea hydrogen peroxide as oxidants and unfunctionalized alkenes as substrates. With several soluble carboxylate salts as additives, like ammonium acetate, ammonium formate, sodium acetate and sodium benzoate, good yields (62-73%) and moderate enantioselectivities (ee 61-69%) were obtained in the asymmetric epoxidation of 1,2-dihydronaphthalene. The results were better than with Ai-heterocycles like Ai-methylimidazole, ferf-butylpyridine. 

SCHEME 91. Asymmetric epoxidation of 1,2-dihydronaphthalene using chiral Mn-salen complexes 173b and 173c... 

The crude mixture was monitored by chiral stationary phase (CSP) HPLC (eluent hexane/isopropanol 95/5, 0.5mLmin, Chiralcel OD-H). After 2 h, (i/f,25)-l-phenyl-3,4-dihydronaphthalene oxide (80% ee) was obtained as the major enantiomer (fR=13.9 min) with 100% conversion (calculated using the internal standard) the minor 1S,2R) enantiomer eluting first (rR=10.1 min). 

Trisubstituted alkenes (1,2-diphenylpropene, 1-methyl-3,4-dihydronaphthalene) have been hydrogenated with excellent optical yields (83-99% ee) in the presence of a chiral bis(tetrahydroindenyl)titanocene catalyst.159... 

Chiral-trans-l,2-disubstituted-l,2-dihydronaphthalenes (cf. 12, 310-311).1 Addition of an organolithium to chiral (l-naphthalyl)oxazolines (2, derived from 1) followed by quenching with CF3COOH results in the salt 3. This product is reduced by LiAlH4 to a single frans-l,2-diaxial diastereomer 4. 

Chiral Katsuki-type salen catalyst has been recycled several times following its use in a model epoxidation reaction of 1,2-dihydronaphthalene in an ionic liquid. The enantioselectivity was comparable to that in dichloromethane, but recovery of the catalyst was easier and the activity was higher.165... 

This possibility of intimate association of rhodium with the aromatic ring suggests further experiments. A logical extension of asymmetric syntheses involving prochir-al reactants is a kinetic resolution with related chiral reactants under similar conditions. In the one case of hydroboration-amination where this has been applied, it has proved to be very effective. The reactant was prepared directly by a Heck reaction on 1,2-dihydronaphthalene, and under the standard conditions of catalytic hydrobora-tion gave >45% of both enantiomerically pure recovered alkene with (after oxidative work-up) the alcohol of opposite hand, mainly as the trans-isomer. This procedure forms a simple and potentially useful route to pharmacologically active substances, demonstrated by the racemic synthesis shown [105] (Scheme 34). 

Yang ( / /. have investigated a series of C 2-symmetric chiral ketones based on the 2,2-bis(diphenyl-phosphanyl)-l,l-binaphthyl (BINAP) skeleton. The asymmetric epoxidation of phenylcyclohexene (and in one example dihydronaphthalene) was achieved in good yields and levels of enantioselectivity (Figure 12) <1996JA491, 1998JA5943, 2004ACR497>. 

Yang and co-workers have suggested that the inherent difficulties in the preparation/isolation of unstable exocyclic iminium salts can be overcome by in situ formation of the catalytic species from chiral pyrrolidines and aldehydes. The catalytic asymmetric epoxidation of phenylcyclohexene and dihydronaphthalene mediated by the iminium salt derived from pyrrolidine 67 and aldehyde 68 has been examined (Scheme 27) <20010L2587>. 

Diels-Alder Reactions. Reagent 1 is useful as an efficient chiral dienophile in asymmetric Diels-Alder reactions. Reaction of 1 with cyclopentadiene in the presence of a Lewis acid occurs with high stereoselectivity. Reaction with 6-methoxy-l-vinyl-3,4-dihydronaphthalene in the presence of EtAlCh proceeds with... 

The angular 7a-phenyl hicyclic lactam can he prepared hy the cyclocondensation of 3-henzoylpropionic acid and (S)-valinol in 85% yield. Dialkylation of this lactam also affords cleanly the a,a-disubstituted compound. Lactam hydrolysis releases chiral, nonracemic a,a-disuhstimted y-keto carboxylic esters (or acids) (eq 5) and 3,3-disuhstituted dihydronaphthalenes may he obtained via cyclization. ... 

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