Intermolecular reactions enantioselectivity

As in intermolecular reactions, enantioselectivity can be achieved in IMDA additions by use of chiral components. For example, the dioxolane ring in 5 and 6 results in TS structures that lead to enantioselective reactions.130 The chirality in the dioxolane ring is reflected in the respective TSs, both of which have an endo orientation of the carbonyl group. 

When guest molecules are arranged together in the channel of a host-guest inclusion complex, intermolecular reactions of the guest compound may proceed stereoselec-tively and efficiently. An enantioselective reaction is expected when optically active host compounds are used. 

Shibasaki and coworkers [87] described the first enantioselective combination of this type in their synthesis of halenaquinone (6/1-162) (Scheme 6/1.43). The key step is an intermolecular Suzuki reaction of 6/1-159 and 6/1-160, followed by an enantioselective Heck reaction in the presence of (S)-BINAP to give 6/1-161. The ee-value was good, but the yield was low. 

Chiral dirhodium(II) catalysts with carboxylate or carboxamidate ligands have recently been developed to take advantage of their versatility in metal carbene transformation, and these have now become the catalysts of choice for cyclopropanation. Chiral carboxylate ligands 195,103 196,104 and 197105 have been used for tetrasubstitution around a dirhodium(II) core. However, the enantioselectivity in intermolecular reactions with simple ketenes is marginal. 

Intermolecular, enantioselective Heck reactions require a cyclic olefin as substrate, since syn carbopal-ladation of a cyclic olefin results in a geometrically defined a-alkyl-palladium compound. By necessity, the subsequent syn dehydropalladation must take place away from the newly formed chiral centre, thereby affording a chiral product. 

The development of catalytic asymmetric reactions is one of the major areas of research in the field of organic chemistry. So far, a number of chiral catalysts have been reported, and some of them have exhibited a much higher catalytic efficiency than enzymes, which are natural catalysts.111 Most of the synthetic asymmetric catalysts, however, show limited activity in terms of either enantioselectivity or chemical yields. The major difference between synthetic asymmetric catalysts and enzymes is that the former activate only one side of the substrate in an intermolecular reaction, whereas the latter can not only activate both sides of the substrate but can also control the orientation of the substrate. If this kind of synergistic cooperation can be realized in synthetic asymmetric catalysis, the concept will open up a new field in asymmetric synthesis, and a wide range of applications may well ensure. In this review we would like to discuss two types of asymmetric two-center catalysis promoted by complexes showing Lewis acidity and Bronsted basicity and/or Lewis acidity and Lewis basicity.121... 

In a rather elegant approach towards colombiasin A (36) Flynn et al. [47] would access the tetracyclic carbon skeleton through an enantioselective intermolecular Diels-Alder sulfoxide elimination-intramolecular Diels-Alder (DA-E-IMDA) sequence between double-diene 166 and quinone 167 (Scheme 26). A key element of the proposed approach would be the chiral sulfoxy group in 167 which controls both the regio and facial selectivity of the intermolecular Diels-Alder reaction and eliminates generation of the dienophile for the IMDA reaction. 

Few examples of preparatively useful intermolecular C-H insertions of electrophilic carbene complexes have been reported. Because of the high reactivity of complexes capable of inserting into C-H bonds, the intermolecular reaction is limited to simple substrates (Table 4.9). From the results reported to date it seems that cycloalkanes and electron-rich heteroaromatics are suitable substrates for intermolecular alkylation by carbene complexes [1165]. The examples in Table 4.9 show that intermolecular C-H insertion enables highly convergent syntheses. Elaborate structures can be constructed in a single step from readily available starting materials. Enantioselective, intermolecular C-H insertions with simple cycloalkenes can be realized with up to 93% ee by use of enantiomerically pure rhodium(II) carboxylates [1093]. 

Two precedent examples had been reported of the enantioselective [2+2+2] cycloaddition of alkynes. In one case, an enantioposition-selective intermolecular reaction of a triyne with acetylene generated an asymmetric carbon at the benzylic position of a formed benzene ring [19]. In the other case, an intramolecular reaction of a triyne induced helical chirality [20]. Both reactions were developed by chiral Ni catalysts. 

Highly enantioselective intermolecular C-H insertion into cyclohexane and cyclopentane is possible using the Rh2(S-DOSP)4 carbenoids generated from aryl diazoacetates 172 to form 173 (Eq. 21) [121, 130]. The enantioselectivity is enhanced when the reactions are conducted at lower temperatures, without any deleterious effect on the catalytic activity or product yield [130]. Extending the reaction to other cyclic and acyclic hydrocarbons has revealed a dehcate balance required between the steric environment and the electronic state of the carbon undergoing C-H insertion [130]. The decreasing enantioselectivity and yield of C-H insertion into adamantane 174 (67% yield, 90% ee). 

Following the success with cobalt and rhodium, Shibata reported Ir(i)-based enantioselective catalytic reaction. Right after their observation that the efficiency of [IrCl(COD)]2-catalyzed PKR substantially increased by addition of a phosphane co-ligand, they moved directly to use chiral phosphanes and examined the enantioselectivity. " TON and TOE of the reaction were low and the number of examples was limited. Typically, the reaction required a fair amount of Ir(i) catalyst [IrCl(COD)]2 (0.1-0.15 equiv.) and (reaction time. However, this has remained as the best in terms of enantioselectivity to date. Moreover, this catalytic system provided the first asymmetric intermolecular reaction as well. 

The final modes of enantioselective allyl alkylations catalyzed by palladium involve the use of chiral nucleophiles447 and chiral leaving groups.448-449 Chiral enamines were found to undergo allylation in 100% optical yield in an intramolecular case and in up to 50% optical yield in intermolecular reactions (equation 358). 

Utilization of an oxygen nucleophile gives similar results (Scheme 8E.35). Whereas modest enantioselectivities (7-54% ee) have been recorded with various ligands [177], the use of 5 results in the efficient cyclization of phenol to furnish the nucleus of tocopherol (vitamin E) with 86% ee [178], Extension of this methodology to intermolecular reactions requires control of regiochemistry, a problem that is not present in the corresponding intramolecular... 

C. Enantioselective Intermolecular Photocyclization Reactions of Achiral Molecules in Inclusion Complex With a Chiral Host Compound... 

An enantioselective intermolecular Michael addition of aldehydes (138) to enones (139), catalysed by imidazolidinones (140), has been reported. Chemoselectivity (Michael addition versus aldol) can be controlled through judicious choice of hydrogen bond-donating co-catalysts. The optimal imidazolidinone-hydrogen bond donor pair affords Michael addition products in <90% ee. Furthermore, the enamine intermediate was isolated and characterized and its efficacy as a nucleophile in the observed Michael addition reactions was demonstrated.172... 

Unfortunately, the chiral bicyclic triazolium salt that had been found to be an excellent catalyst for the enantioselective intermolecular benzoin condensation proved to be ineffective in the intramolecular reaction. In searching for alternative catalysts, we synthesized the novel triazolium salts 19 and 20, starting from easily accessible enantiopure polycyclic y-lactams (Schemes 9.4 and 9.5) that finally delivered good results in the enantioselective intramolecular cross-benzoin condensation [35]. 

In enantioselective photocycloaddition reactions, 4-alkoxyquinolones perform in superior fashion to l,5-dihydropyrrol-2-ones and 5,6-dihydro-lff-pyridin-2-ones. Both, intermolecular and intramolecular reactions were performed with excellent enantioselectivity in the presence of the chiral template 115, or of its enantiomer ent-115 [147, 148], The well-established photocycloaddition reactions [149, 150] enabled access to a variety of chiral dihydroquinolones. 4-Methoxyquinolone (157) produced, upon direct irradiation in the presence of allyl acetate, the formal HT product 158 in 80% yield and with 92% ee (Scheme 6.56) [151]. 

Bach, T. and Bergmann, H. (2000) Enantioselective intermolecular [2 + 2]-photocycloaddition reactions of alkenes... 

Unfortunately the bicyclic triazolium salt that had successfully been used in our research group for the enantioselective intermolecular benzoin condensation (Enders and Kallfass 2002) did not show any catalytic activity in the intramolecular reaction. We thus searched for alternative, easily accessible enantiopure polycyclic y-lactams as precursors for the synthesis of novel triazolium salts (Enders et al. 2006c for a related study see Takikawa et al. 2006). The rigid polycyclic structure of the catalysts should allow high asymmetric inductions. A first tar-... 

Bach T, Bergmann H (2000) Enantioselective intermolecular [2+21-photo-cycloaddition reactions of alkenes and a 2-quinolone in solution. J Am ChemSoc 122 11525-11526... 

Enantioselective Intermolecular Cyclopropenation Reactions. The use of Rh2(MEPY)4 catalysts for intermolecular cyclopropenation of 1-alkynes results in moderate to high selectivity. With propargyl methyl ether (or acetate), for example, reactions with (—)-menthyl [(+)-(l/ ,25,5/ )-2-isopropyT5-methyl-1-cyclohexyl] diazoacetate catalyzed by Rh2(55 -MEPY)4 produces the corresponding cyclopropene product (eq 3) with 98% diastere-omeric excess (de). ... 

Yamamoto s catalyst has been applied to the enantioselective intramolecular Diels-Alder reaction (Eq. 12) [11]. The same aldehyde devoid of a methyl group in the a position affords the adduct with 46 % ee (for the endo isomer) and exo. endo = 1 99. An a substituent is essential for high ee, as observed in the intermolecular reaction. 

Dirhodium(II) catalysts that possess chiral 2-pyrrolidone-5-carboxylate ester ligands (mepy) are the most effective among those of dirhodium or copper for highly diastereoselective and enantioselective intermolecular cyclopropenation reactions between l-alkynes and diazoesters (eq. (9)). Product yields are moderate, and enantiomeric excesses range from 40 to 98 %. Interestingly, the (R) or (5) catalyst produces the cyclopropene-l-carboxylate respectively with the (/ ) or (5) configuration [26]. 

Castro, J., Moyano, A., Pericas, M. A., Riera, A., Alvarez-Larena, A., Piniella, J. F. Acetylene-Dicobaltcarbonyl Complexes with Chiral Phosphinooxazoline Ligands Synthesis, Structural Characterization, and Application to Enantioselective Intermolecular Pauson-Khand Reactions. J. Am. Chem. Soc. 2000,122, 7944-7952. 

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