Enantioselective intermolecular

Although the enantioselective intermolecular addition of aliphatic alcohols to meso-epoxides with (salen)metal systems has not been reported, intramolecular asymmetric ring-opening of meso-epoxy alcohols has been demonstrated. By use of monomeric cobalt acetate catalyst 8, several complex cyclic and bicydic products can be accessed in highly enantioenriched form from the readily available meso-epoxy alcohols (Scheme 7.17) [32]. 

Scheme 3.36. Enantioselective intermolecular domino radical addition procedure.

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]. 

Experimental Procedure 4.2.9. Enantioselective, Intermolecular Cyclopropana-tion Ethyl (15)-2,2-Dimethyl-l-cyclopropanecarboxylate... 

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). 

Good yields of the bridged tetrahydropyran-3-one 38 are obtained when the a-diazoketones 37 are decomposed by chiral Rh(II)-catalysts in the presence of DMAD. It is proposed that an enantioselective intermolecular 13-dipolar cycloaddition follows the generation of a carbonyl ylide which is bound to the rhodium (Scheme 21) <99JA1417>. 

At the beginning of our investigations enantioselective intermolecular oxa-Michael additions with removable chirality information in the oxygen-nucleophile had not been reported. Therefore we developed a highly diastereo- and enantiose-... 

In summary, the metal-catalyzed decomposition of diazo compounds results in a broad array of opportunities for the development of new asymmetric catalytic transformations. In the last few years considerable advances have been made in enantioselective intermolecular C-H insertion, novel cycloadditions, and tandem cyclization/cycloadditions. These new transformations offer new strategies for the rapid enantioselective construction of complex structures. 

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... 

Donor/acceptor-substituted carbenoids are usually much more chemoselective than the more established carbenoids functionalized solely with acceptor groups [lc]. The development of these donor/acceptor-substituted carbenoids has enabled enantioselective intermolecular C-H insertions to become a very practical process. These carbenoids have a strong preference for functionalizing C-H bonds where positive charge build-up at C in the transition state is favored but these electronic effects are counter-balanced by steric factors. Benzylic and allylic sites and C-H bonds adjacent to oxygen and nitrogen functionality are favored but these sites can also be sterically protected if desired. By appropriate consideration of the regiocontrolling elements, effective intermolecular C-H insertions at methyl, methylene, and methine sites have been achieved. 

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]. 

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

The game is certainly not over, very recently catalytic enantioselective intermolecular cycloadditions of 2-diazo-3,6-diketoester of type 68 derived carbonyl ylides with alkene dipolarophiles have been developed [57]. Relying on chiral rhodium(II) clusters I and II, Hodgson et al. obtained very high enantioselectivities (up to 92% ee on 69) with norbornene as a trap, as disclosed in Scheme 31. 

Irradiation of solid 1 1 complexes of benzaldehyde 89 and P-cyclodextrin 2 resulted in enantioselective intermolecular hydrogen abstraction and radical coupling to afford (/ )-( — )-benzoin 90 as a major product in up to 15% ee and 56% chemical yield. 4-Benzoylbenzaldehyde was obtained as a minor product (Scheme 20) [22]. This reactivity can be understood from the presence of guest-to-host (2 2) complexes generated by the head-to-head association of two 1 1 inclusion complexes. 

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-... 

Mennen MS, Gipson JD, Kim YR, Miller SJ (2005a) Thiazolylalanine-derived catalysts for enantioselective intermolecular aldehyde-imine cross-couplings. J Am Chem Soc 127 1654... 

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). ... 

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. 

Scheme 12.16 Rh2 (S) nta 4 catalyzed enantioselective intermolecular C H amination (nttl,...

Of particular note, enantioselective intermolecular allylic amination is also pos sible using this protocol, and no competing aziridination is observed. Cyclic and linear alkenes were selectively aminated with high selectivities (27-31). 

The thiazolium-catalyzed addition of an aldehyde-derived acyl anion with a Michael acceptor (Stetter reaction) is a well-known synthetic tool leading to the synthesis of highly funtionalized products. Recent developments in this area include the thiazolylalanine-derived catalyst 191 for asymmetric intramolecular Stetter reaction of a,P-unsaturated esters <05CC195>. However, these cyclizations proceed only in moderate enantioselectivities and yields even under optimized conditions. Thiazolium salt 191 has been used successfully for enantioselective intermolecular aldehyde-imine cross coupling reactions <05JA1654>. Treatment of tosylamides 194 with aryl aldehydes in the presence of 15 mol% of 191 and 2... 

Substantial progress has also been made in the chiral auxiliary-based approach to an enantioselective intermolecular Pauson-Khand reaction. Initial studies utilizing alkynes substituted with fra s-2-phenylcyclohexanol produced cyclopentenones with low drs, however, the diastereomers were easily separable... 

Keywords Rhodium, Carbon-Hydrogen Insertion, Cyclopropanation, Chiral, Asymmetric, Enantioselective, Intermolecular, Intramolecular, Diazocarbonyl Compounds... 

The cyclisation of nitrones derived from tryptamines is a similar process and can be carried out enanti-oselectively using a chiral Lewis acid."° A similar enantioselective intermolecular process is the copper-catalysed reaction of indoles with tosyl-imines of aromatic aldehydes. "... 

The intermolecular asymmetric Heck reaction, a palladium-catalysed carbon-carbon bond forming process, is an efficient method for the preparation of optically active cyclic compounds.[1] Very recently, a new catalytic system has been developed based on palladium complexes having l-[4-(5)-tert-butyl-2-oxazolin-2-yl]-2-(5)-(diphenylphosphino)ferrocene (1) as the chiral ligand121 (Figure 5.2), which we have shown to be efficient catalysts for the enantioselective intermolecular Heck reaction of 2,3-dihydrofuran (2).[3] In contrast to complexes derived... 

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