Term Project 1 Example 2
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Term Project 1 Example 2
Jessica P. Shackleford Chemical Literature December 12, 2008 Chemical Literature Annotated Bibliography Topic: Mechanisms and/or Methods of Enantioselective Lewis Acid Catalysis Key Paper: Mechanistic Studies of the Zirconium-Triisopropanolamine-Catalyzed Enantioselective Addition of Azide to Cyclohexene Oxide (1998) SciFinder Years: 1993-2008 (36 Papers) SciFinder Search Additional Information: • 4 papers published prior to 1998 • 2 papers published in 1998 (Including the key paper) • 30 papers published after 1998 Science Citation Index Key Paper Years: 1998-2008 Science Citation Index Search Additional Information: • Key paper cited on average 3 times per year • Key paper cited overall 34 times • If a paper was considered closely related to the topic, an entry in cycle A, B, or C will be found in this document • If the paper was considered unrelated, it was intentionally left out and no entry will be found 1 Annotated Bibliography of all References After and During 1998 1. Paull, D. H.; Abraham, C. J.; Scerba, M. T.; Alden-Danforth, E.; Lectka, T. Accounts of Chemical Research 2008, 41, 655-663. A review. In the field of catalytic, asym. synthesis, there is a growing emphasis on multifunctional systems, in which multiple parts of a catalyst or multiple catalysts work together to promote a specific reaction. These efforts, in part, are result-driven, and they are also part of a movement toward emulating the efficiency and selectivity of nature's catalysts, enzymes. In this Account, we illustrate the importance of bifunctional catalytic methods, focusing on the cooperative action of Lewis acidic and Lewis basic catalysts by the simultaneous activation of both electrophilic and nucleophilic reaction partners. For our part, we have contributed three sep. bifunctional methods that combine achiral Lewis acids with chiral cinchona alkaloid nucleophiles, for example, benzoylquinine (BQ), to catalyze highly enantioselective cycloaddn. reactions between ketene enolates and various electrophiles. Each method requires a distinct Lewis acid to coordinate and activate the electrophile, which in turn increases the reaction rates and yields, without any detectable influence on the outstanding enantioselectivities inherent to these reactions. To place our results in perspective, many important contributions to this emerging field are highlighted and our own reports are chronicled. 2. Pan, S. C.; List, B. Ernst Schering Foundation Symposium Proceedings 2008, 1-43. Organocatalysis, catalysis with low-mol. wt. catalysts in which a metal is not part of the catalytic principle or the reaction substrate, can be as efficient and selective as metal- or biocatalysis. Important discoveries in this area include novel Lewis base-catalyzed enantioselective processes and, more recently, simple Bronsted acid organocatalysts that rival the efficiency of traditional metal-based asym. Lewis acid-catalysts. Contributions to organocatalysis from our labs. include several new and broadly useful concepts such as enamine catalysis and asym. counteraniondirected catalysis. Our lab. has discovered the proline-catalyzed direct asym. intermol. aldol reaction and introduced several other organocatalytic reactions. 3. Marcelli, T.; Hammar, P.; Himo, F. Chemistry--A European Journal 2008, 14, 8562-8571. The phosphoric acid catalyzed reaction of 1,4-dihydropyridines with N-arylimines has been investigated by using d. functional theory. We first considered the reaction of acetophenone PMP-imine (PMP = p-methoxyphenyl) with the di-Me Hantzsch ester catalyzed by di-Ph phosphate. Our study showed that, in agreement with what has previously been postulated for other reactions, di-Ph phosphate acts as a Lewis base/Broensted acid bifunctional catalyst in this transformation, simultaneously activating both reaction partners. The calcns. also showed that the hydride transfer transition states for the E and Z isomers of the iminium ion have comparable energies. This observation turned out to be crucial to the understanding of the enantioselectivity of the process. Our results indicate that when using a chiral 3,3'-disubstituted biaryl phosphoric acid, hydride transfer to the Re face of the (Z)-iminium is energetically more favorable and is responsible for the enantioselectivity, whereas the corresponding transition states for nucleophilic attack on the two faces of the (E)-iminium are virtually degenerate. Moreover, model calcns. predict the reversal in enantioselectivity obsd. in the hydrogenation of 2-arylquinolines, which during the catalytic cycle are converted into (E)-iminium ions that lack the flexibility of those derived from acyclic N-arylimines. In this respect, the conformational 2 rigidity of the dihydroquinolinium cation imposes an unfavorable binding geometry on the transition state for hydride transfer on the Re face and is therefore responsible for the high enantioselectivity. 4. Pan, S. C.; List, B. Ernst Schering Foundation symposium proceedings 2007, 1-43. Organocatalysis, catalysis with low-molecular weight catalysts in which a metal is not part of the catalytic principle or the reaction substrate, can be as efficient and selective as metal- or biocatalysis. Important discoveries in this area include novel Lewis base-catalyzed enantioselective processes and, more recently, simple Bronsted acid organocatalysts that rival the efficiency of traditional metal-based asymmetric Lewis acid-catalysts. Contributions to organocatalysis from our laboratories include several new and broadly useful concepts such as enamine catalysis and asymmetric counteranion-directed catalysis. Our laboratory has discovered the proline-catalyzed direct asymmetric intermolecular aldol reaction and introduced several other organocatalytic reactions. 5. Masson, G.; Housseman, C.; Zhu, J. Angewandte Chemie, International Edition 2007, 46, 46144628. This review summarizes recent mechanistic insights and advances in the design and synthesis of small org. mol. catalysts for enantioselective MBH and aza-MBH reactions. 6. Carmona, D.; Lamata, M. P.; Viguri, F.; Rodriguez, R.; Barba, C.; Lahoz, F. J.; Martin, M. L.; Oro, L. A.; Salvatella, L. Organometallics 2007, 26, 6493-6496. The Diels-Alder reaction between methacrolein and cyclopentadiene catalyzed by [(h5C5Me5)Ir1(methacrolein)][SbF6]2 [2, (R)-Prophos = (R)-1,2-bis(diphenylphosphino)propane] is inhibited by the products, this feature allowing, for the 1st time, the characterization of the major Lewis acid-product intermediate involving an enal as a dienophile. The authors prepd. and report the spectroscopic and crystallog. characterization of this intermediate Lewis acid-DA product complex [(h5-C5Me5)Ir((R)-Prophos)(exo-(S)-adduct)][SbF6]2 (1) [exo-(S)-adduct = (1R,2S,4R)-2-methylbicyclo[2.2.1]hept-5-ene-2-carboxaldehyde]. 7. Luo, H.-K.; Schumann, H. Journal of Molecular Catalysis A: Chemical 2006, 248, 42-47. An efficient direct activation method was developed to transfer diastereopure l-[(BIPHEP)Pt(SBINOL)] to highly active and selective enantiopure Lewis acid l-[(BIPHEP)Pt](SbF6)2 by silver hexafluoroantimonate (AgSbF6) for the enantioselective carbonyl-ene reactions. Both enantioselective glyoxylate-ene reactions between Et glyoxylate and alkenes, and enantioselective carbonyl-ene reactions between phenylglyoxal and alkenes were studied demonstrating good catalytic activity and enantioselectivity. Particularly, for the enantioselective carbonyl-ene reaction between phenylglyoxal and 2,3-dimethyl-1-butene, the Lewis acid catalyst l-[(BIPHEP)Pt](SbF6)2 generated with this direct activation method by silver hexafluoroantimonate (AgSbF6) could give excellent ee values high up to 94%. 8. Yamagiwa, N.; Qin, H.; Matsunaga, S.; Shibasaki, M. Journal of the American Chemical Society 2005, 127, 13419-13427. The full details of a catalytic asym. aza-Michael reaction of methoxylamine promoted by rare earth-alkali metal heterobimetallic complexes are described, demonstrating the effectiveness of Lewis acid-Lewis acid cooperative catalysis. First, enones were used as substrates, and the 1,4adducts were obtained in good yield (57-98%) and high ee (81-96%). Catalyst loading was successfully reduced to 0.3-3 mol% with enones. To broaden the substrate scope of the reaction 3 to carboxylic acid derivs., a,b-unsatd. N-acylpyrroles were used as monodentate, carboxylic acid derivs. With b-alkyl-substituted N-acylpyrroles, the reaction proceeded smoothly and the products were obtained in high yield and good ee. Transformation of the 1,4-adducts from enones and a,b-unsatd. N-acylpyrroles afforded corresponding chiral aziridines and b-amino acids. Detailed mechanistic studies, including kinetics, NMR anal., nonlinear effects, and rare earth metal effects, are also described. The Lewis acid-Lewis acid cooperative mechanism, including the substrate coordination mode, is discussed. 9. France, S.; Shah, M. H.; Weatherwax, A.; Wack, H.; Roth, J. P.; Lectka, T. Journal of the American Chemical Society 2005, 127, 1206-1215. We report a mechanistically based study of bifunctional catalyst systems in which chiral nucleophiles work in conjunction with Lewis acids to produce b-lactams in high chem. yield, diastereoselectivity, and enantioselectivity. For example, reacting PhCH2COCl with CH:C(CO2Et)NSO2C6H4Me-4 in the presence of 1,4-bis(dimethylamino)naphthalene as proton sponge and quinine catalyst I gave b-lactam II in 95% yield using In(OTf)3 with 98% ee. Chiral cinchona alkaloid derivs. work best when paired with Lewis acids based on Al(III), Zn(II), Sc(III), and, most notably, In(III). Homogeneous bifunctional catalysts, in which the catalyst contains both Lewis acidic and Lewis basic sites, were also studied in detail. Mechanistic evidence allows us to conclude that the chiral nucleophiles form zwitterionic enolates that react with metalcoordinated imines. Alternative scenarios, which postulated metal-bound enolates, were disfavored on the basis of our observations. 10. Fennie, M. W.; DiMauro, E. F.; O'Brien, E. M.; Annamalai, V.; Kozlowski, M. C. Tetrahedron 2005, 61, 6249-6265. Metal complexes of C2-sym. Lewis acid/Lewis base salen ligands provide bifunctional activation resulting in rapid rates in the enantioselective addn. of diethylzinc to aldehydes (up to 92% ee). Further expts. probed the reactivity of the individual Lewis acid and Lewis base components of the catalyst and established that both moieties are essential for asym. catalysis. These catalysts are also effective in the asym. addn. of diethylzinc to a-ketoesters. This finding is significant because a-ketoesters alone serve as their own ligands to accelerate racemic 1,2-carbonyl addn. of Et2Zn and racemic carbonyl redn. The latter proceeds via a metallocene pathway, and often accounts for the predominant product. Singular Lewis acid catalysts do not accelerate enantioselective 1,2-addn. over these two competing paths. The bifunctional amino salen catalysts, however, rapidly provide enantioenriched 1,2-addn. products in excellent yield, complete chemoselectivity, and good enantioselectivity (up to 88% ee). A library of the bifunctional amino salens was synthesized and evaluated in this reaction. The utility of the aketoester method has been demonstrated in the synthesis of an opiate antagonist. 11. Kennedy, J. W. J.; Hall, D. G. Journal of Organic Chemistry 2004, 69, 4412-4428. A full account of the development of the first catalytic manifold for the addns. of allylboronates to aldehydes is described. The thermal addns. (both diastereospecific and enantioselective) of 2carboxyester 3,3-disubstituted allylboronates to both arom. and aliph. aldehydes give biol. and synthetically important exo-methylene butyrolactones contg. a b-quaternary carbon center. Although the thermal reaction requires 14 d at room temp. to reach completion, the presence of certain metal salts allows for a 12-16 h reaction while preserving the diastereospecificity obsd. in the uncatalyzed process. Preliminary mechanistic studies on the origin of the catalytic effect are described as well as stereoselective transformations of lactones into cyclic and acyclic stereotriads with potential usefulness as synthetic intermediates. 4 12. Kanemasa, S.; Ito, K. European Journal of Organic Chemistry 2004, 4741-4753. A review. An effective enantioselective synthetic method based on a new concept of double catalytic activation has been developed, in which both electrophile and nucleophile precursors are activated by use of catalytic amts. of chiral Lewis acid and amine base, resp. This method has been successfully applied to enantioselective thiol conjugate addns., as well as to Michael reactions of malononitrile, nitromethane, and cyclic 1,3-dicarbonyl compds. in the presence of DBFOX/Ph-nickel(II) aqua complexes with amines. This new method should be a powerful tool, esp. when single catalytic activation of either nucleophiles or electrophiles is not sufficient to induce bond formation. 13. Chen, F.-X.; Zhou, H.; Liu, X.; Qin, B.; Feng, X.; Zhang, G.; Jiang, Y. Chemistry--A European Journal 2004, 10, 4790-4797. Double-activation catalysis promises high catalytic efficiency in the enantioselective cyanosilylation of ketones through the combined use of a Lewis acid and a Lewis base. Catalyst systems composed of a chiral salen-Al complex and an N-oxide have high catalytic turnovers (200 for arom. ketones, 1000 for aliph. ones). With these catalysts, a wide range of aliph. and arom. ketones were converted under mild conditions into tertiary cyanohydrin O-TMS ethers, e.g., I, in excellent yields and with high enantioselectivities. Preliminary mechanistic studies revealed that the salen-Al complex played the role of a Lewis acid to activate the ketone and the N-oxide that of a Lewis base to activate TMSCN; i.e., double activation. 14. Carmona, D.; Lamata, M. P.; Viguri, F.; Rodriguez, R.; Oro, L. A.; Balana, A. I.; Lahoz, F. J.; Tejero, T.; Merino, P.; Franco, S.; Montesa, I. Journal of the American Chemical Society 2004, 126, 27162717. The 1,3-dipolar cycloaddn. reaction of C,N-diphenylnitrone with methacrolein is efficiently catalyzed by the Rh diphosphine compd. (SRh,RC)[(h5-C5Me5)Rh(R-Prophos)(H2O)](SbF6)2 [RProphos = (R)(+)-1,2-bis(diphenylphosphino)-propane, 1.SbF6]; the asym. catalytic process occurs with reversal of regioselectivity, perfect endo selectivity, and up to 92% ee. The complete (NMR and x-ray anal.) characterization of the involved intermediate (SRh,RC)[(h5-C5Me5)Rh(RProphos)(methacrolein)](SbF6)2 (7.SbF6) allows us to interpret the obsd. selectivity. 15. Bachmann, S.; Knudsen, K. R.; Jorgensen, K. A. Organic & Biomolecular Chemistry 2004, 2, 20442049. Attempts are made to build a bridge between asym. catalysis and enzymic reactions by mechanistic investigations and the development of a catalytic and enantioselective approach to amination of a-keto esters by primary amines catalyzed by chiral Lewis acids as a model for transamination enzymes. Different Lewis acids can catalyze the half-transamination of a-keto esters using primary amine nitrogen sources such as pyridoxamine and 4-picolylamine. The mechanistic studies of the Lewis-acid catalyzed half-transamination using deuterium-labeled compds. show the incorporation of deuterium atoms in several positions of the a-amino acid deriv., indicating that the enol of the a-keto ester plays an important role along the reaction path. The catalytic enantioselective reactions are dependent on the pKa-value of the solvent since enantioselectivities were only obtained in solvents with high pKa-values relative to methanol. However, stronger acidic conditions generally gave better yields, but poor enantioselectivities. A series of chiral Lewis acids were screened as catalysts for the enantioselective half-transamination reactions and moderate yields and enantioselectivities of up to 46% ee were obtained. 5 16. Ohsugi, S.-i.; Nishide, K.; Node, M. Tetrahedron 2003, 59, 1859-1871. The first tandem cationic [4++2] polar cycloaddn.-elimination reaction of 1-thia-1,3-butadienyl cations with olefins to afford directly 3,4-dihydro-2H-thiopyrans is described. These cations were easily accessible by treatment of monothioacetals, particularly the 2-alkenyl-4,4-dimethyl1,3-oxathianes, with a hard Lewis acid. In this novel reaction, 2-alkenyl-4,4-dimethyl-1,3oxathianes were utilized as synthetic equiv. for highly reactive a,b-unsatd. thioaldehydes. The effect of geminal di-Me substituents on the oxathianes and the mechanistic aspect of the reaction are considered. The reaction's asym. version was also investigated using a chiral oxathiane derived from (-)-(1R,2R,5R)-2-(1-mercapto-1-methylethyl)-5-methylcyclohexanol. Although the enantioselectivities were moderate, the whole process can be done under odorless conditions. 17. Denmark, S. E.; Fu, J. Chemical Reviews (Washington, DC, United States) 2003, 103, 2763-2793. A review discusses the enantioselective allylation of aldehydes and ketones with a variety of allylmetal reagents to provide nonracemic homoallylic alcs. The mechanism of and chiral Lewis acid catalysts for the addn. of allylic silanes, stannanes and boranes to aldehydes and ketones, catalytic enantioselective allylation reactions with allylic halides, Lewis base-catalyzed enantioselective allylation with allylic trichlorosilanes, and allenylation and propargylation of aldehydes are discussed in the review; a table of conditions and selectivities for the enantioselective allylation of a variety of substrates is also provided. 18. Cheng, H.-S.; Loh, T.-P. Journal of the American Chemical Society 2003, 125, 4990-4991. A novel and general method for the a-regioselective prenylation of aldehydes RCHO [R = n-octyl, Ph, PhCH2CH2, PhCH2O(CH2)4, 2-naphthyl, etc.] employs chiral g-prenyl-1,5-diol H2C:CHCMe2CH(OH)(CH2)4OH as the prenyl source in the presence of a catalytic amt. of Lewis or Bronsted acid and affords the corresponding allylic alcs. RCH(OH)CH2CH:CMe2 in good yields (up to 95%) and with excellent enantioselectivities (up to 98% ee). Furthermore, the reaction is highly chemoselective and occurs selectively with the aldehyde without affecting the enone and the a,b-unsatd. ester functionalities. Detailed mechanistic studies disclose the facile epimerization of arom. alc. in dichloromethane in the presence of In(OSO2CF3)3. The use of non-polar solvents such as hexane in the presence of In(OSO2CF3)3 or F3CSO2OH effectively suppresses this epimerization. 19. Chen, F.; Feng, X.; Qin, B.; Zhang, G.; Jiang, Y. Organic Letters 2003, 5, 949-952. Enantioselective addn. of TMSCN to ketones is achieved by a catalytic double-activation method using I-Ti(IV) complex as the Lewis acid and achiral N-oxide II as the Lewis base to activate ketones and TMSCN, resp. 20. Itoh, K.; Kanemasa, S. Journal of the American Chemical Society 2002, 124, 13394-13395. Reactions of nitromethane with 1-(2-alkenoyl)-3,5-dimethylpyrazoles can be effectively catalyzed by (R,R)-2,2'-(4,6-dibenzofurandiyl)bis[4-phenyloxazoline].Ni(ClO4)2.3H2O and achiral amine bases, each in a catalytic loading of 10 mol %, to give 1-(3-substituted 4-nitrobutanoyl)3,5-dimethylpyrazoles in high chem. yields. Excellent enantioselectivities up to 98% ee have been achieved. The nitro moiety can be easily reduced on Raney nickel at atm. pressure, followed by concurrent cyclization, to give enantiomers of 4-substituted 2-pyrrolidinone derivs. after the usual workup. This method can be successfully applied to a short synthesis of (R)-(-)rolipram. 6 21. Corey, E. J. Angewandte Chemie, International Edition 2002, 41, 1650-1667. A review. One hundred years after the birth of Kurt Alder and seventy-five years after the discovery of his famous reaction, one of the most important and fascinating transformations in chem., research on that process continues to surprise, excite, delight, and inform the chem. community. This article is based on presentations given first at the University of Cologne, Germany (Kurt Alder lecture, 1992), then at the Roger Adams Award Symposium (1993), and later at the Burgenstock Conference of 2001, and describes research by our group on the development and understanding of enantioselective versions of the Diels - Alder reactions. The elements of this review include (1) development of new chiral Lewis acid catalysts for highly enantioselective (>25:1) [4+2] cycloaddns.; (2) the fine mechanistic details and pre-transitionstate assemblies of these reactions; (3) the fundamental understanding of catalytic activity and enantioselectivity for highly enantioselective Diels-Alder processes; and (4) applications to the synthesis of complex mols. The range and power of the Diels-Alder reaction have steadily increased over seven decades. The end of this remarkable development is not in sight, a high compliment to this field of Science and to its great inventor. 22. Roberson, M.; Jepsen, A. S.; Jorgensen, K. A. Tetrahedron 2001, 57, 907-913. The mechanism for the hetero-Diels-Alder reaction of benzaldehyde with Danishefsky's diene catalyzed by various types of achiral and chiral aluminum complexes has been studied from a theor. point of view using semi-empirical and ab initio calcns. The uncatalyzed reaction proceeds as a concerted reaction with an unsym. transition state. The catalytic reaction has been studied using first (MeO)2AlMe, followed by (S)-BINOL-AlMe as the catalysts, and the transition states and intermediates have been calcd. for different reaction paths. The catalyst activates benzaldehyde making the carbon atom in the carbonyl functionality more electrophilic. Attempts to calc. a concerted reaction path failed. However, a two-step process, the first step being a nucleophilic attack of the activated diene to the carbonyl carbon atom, with a transitionstate energy of up to 13 kcal mol-1, depending on the catalyst and calcn. method used, was found to take place leading to an aldol-like local energy-min. intermediate. The second step, the ring-closure, which has a significantly lower transition-state energy leads to the hetero-DielsAlder adduct. The mechanistic aspects of the catalytic hetero-Diels-Alder reaction is discussed on the basis of the calcns. 23. Li, M.; Xie, R.; Tian, A. Science in China, Series B: Chemistry 2001, 44, 616-626. The ab initio MO study on the mechanism of enantioselective redn. of 3,3-di-Me butanone-2 with borane catalyzed by chiral oxazaborolidine is performed. As illustrated, this enantioselective redn. is exothermic and goes mainly through the formations of the catalystborane adduct, the catalyst-borane-3,3-dimethyl butanone-2 adduct, and the catalystalkoxyborane adduct with a B-O-B-N 4-member ring and through the decompn. of the catalystalkoxyborane adduct with the regeneration of the catalyst. During the hydride transfer in the catalyst-borane-3,3-dimethyl butanone-2 adduct to form the catalyst-alkoxyborane adduct, the hydride transfer and the formation of the B-O-B-N 4-member ring in the catalyst-alkoxyborane adduct happen simultaneously. The controlling step for the redn. is the transfer of hydride from the borane moiety to the carbonyl carbon of 3,3-di-Me butanone-2. The transition state for the hydride transfer is a twisted chair structure and the redn. leads to R-chiral alcs. 24. Lautens, M.; Hiebert, S.; Renaud, J.-L. Journal of the American Chemical Society 2001, 123, 68346839. 7 The mechanism of the palladium-catalyzed ring opening of oxabicyclic alkenes with dialkylzinc has been studied. Expts. which rule out a p-allyl mechanism were carried out. Trapping carbometalated products and synthesis and successful reaction of alkyl palladium species provided strong evidence in favor of an enantioselective carbopalladation as the key step in the mechanism. The studies also suggest that a cationic palladium species is responsible for carbopalladation of the alkene. The combination of palladium and dialkylzinc is unique in that the dialkylzinc functions both in the transmetalation to palladium and as a Lewis acid in forming the reactive cationic palladium species. 25. Corey, E. J.; Lee, T. W. Chemical Communications (Cambridge, United Kingdom) 2001, 13211329. A review with refs. X-Ray crystallog. studies have provided exptl. evidence for the existence of intramol. formyl C-H hydrogen bonds to oxygen or fluorine ligands in complexes of aldehydes and boron Lewis acids. This type of hydrogen bond can be regarded as 'induced' or 'cooperative' in the sense that its strength can be expected to increase as the bonding between the formyl oxygen and the Lewis acid becomes stronger. Coplanarity of the formyl group and the metal-X subunit to which it is bound in a five-membered ring effectively restricts rotation about the donor-acceptor bond between the formyl oxygen and the metal center of the Lewis acid, thus creating an addnl. organizing element in these complexes. This organizing element provides a simple and logical basis for understanding the mechanistic basis for enantioselectivity in many reactions of achiral aldehydes which are catalyzed by chiral Lewis acids. These reactions include aldol, allylation and ene addn. to the formyl C:O group and Diels-Alder reactions of a,b-unsatd. aldehydes with 1,3-dienes. The idea of the induced formyl C-H hydrogen bond can serve as a guide in the design of new enantioselective catalysts as well as a mechanistic principle for understanding preferred transition state assemblies. 26. Nakamura, S.; Kaneeda, M.; Ishihara, K.; Yamamoto, H. Journal of the American Chemical Society 2000, 122, 8120-8130. Enantioselective protonation is a potent and efficient way to construct chiral carbons. Here we report details of the reaction using Lewis acid-assisted chiral Bronsted acids (chiral LBAs). The 1:1 coordinate complex of tin tetrachloride and optically active binaphthol ((R)- or (S)-BINOL) can directly protonate various silyl enol ethers and ketene disilyl acetals to give the corresponding a-aryl ketones and a-arylcarboxylic acids, resp., with high enantiomeric excesses (up to 98% ee). A catalytic version of enantioselective protonation has also been achieved using stoichiometric amts. of 2,6-dimethylphenol and catalytic amts. of monomethyl ether of optically active BINOL in the presence of tin tetrachloride. This protonation is also effective for producing a-halocarbonyl compds. (up to 91% ee). DFT calcns. on the B3LYP/LANL2DZ level show that the conformational structure of the chiral LBA and the orientation of activated proton on (R)-BINOLs are important for understanding the abs. stereochem. of the products. 27. MacMillan, D. W. C.; Borths, C. J.; Jen, W. S.; Wiener, J. S.; Paras, N. A.; Wilson, R. M. Abstracts of Papers, 220th ACS National Meeting, Washington, DC, United States, August 20-24, 2000 2000, ORGN-563. Over the past three decades, the capacity to induce asym. transformations using single enantiomer catalysts has become a focal point for extensive research efforts in both industrial and academic settings. During this time, remarkable advances have been made in the development of organometallic asym. catalysts that in turn have provided a wealth of enantioselective oxidn., redn., pi-bond activation and Lewis acid catalyzed processes. In 8 contrast, relatively few asym. transformations have been reported which employ org. mols. as reaction catalysts despite the widespread availability of org. chems. in enantiopure form and the accordant potential for academic, industrial and economic benefit. In this discussion we introduce a new strategy for organocatalysis that is broadly useful for a range of asym. transformations. In this context, we will document the first highly enantioselective organocatalytic Diels-Alder reaction, the first enantioselective organocatalytic 1,3 dipolar cycloaddn. and a new highly enantioselective organocatalytic Michael reaction. 28. Jorgensen, K. A. Angewandte Chemie, International Edition 2000, 39, 3558-3588. A review, with 225 refs., on development of catalytic asym. hetero-Diels-Alder reactions of carbonyl compds. and imines. The Diels-Alder reaction has undergone intensive development and is of fundamental importance for synthetic, phys., and theor. chemists. The prepn. of numerous compds. of importance is based on cycloaddn. reactions to carbonyl compds. and imines. There are several parallels between the reactions of carbonyl compds. and those of imines, which, however, fade on entering the field of catalytic reactions. From a mechanistic point of view some similarities can be drawn, but the synthetic development of catalytic enantioselective hetero-Diels-Alder reactions of imines are several years behind those of the carbonyl compds. For hetero-Diels-Alder reactions of carbonyl compds. there a no. of different chiral catalysts, and great progress was achieved in developing enantioselective reactions for unactivated and activated carbonyl compds. In contrast, the development of catalytic enantioselective hetero-Diels-Alder reactions of imines is in its infancy and only few catalytic reactions published. The synthetic and mechanistic aspects of enantioselective hetero-DielsAlder reaction of carbonyl compds. catalyzed by chiral Lewis acids are discussed. For the heteroDiels-Alder reactions of imines, the diastereoselective reactions of optically substrates catalyzed by Lewis acids and catalytic enantioselective reactions are outlined. 29. Evans, D. A.; Kozlowski, M. C.; Murry, J. A.; Burgey, C. S.; Campos, K. R.; Connell, B. T.; Staples, R. J. Journal of the American Chemical Society 1999, 121, 669-685. C2-Sym. bis(oxazolinyl)pyridine (pybox)-Cu(II) complexes have been shown to catalyze enantioselective Mukaiyama aldol reactions between (benzyloxy)acetaldehyde and a variety of silylketene acetals. The aldol products are generated in high yields and in 92-99% enantiomeric excess using as little as 0.5 mol % of chiral catalyst [Cu((S,S)-Ph-pybox)](SbF6)2 (I.2SbF6; R = Ph). With substituted silylketene acetals, syn reaction diastereoselection ranging from 95:5 to 97:3 and enantioselectivities >=95% are obsd. Investigation into the reaction mechanism utilizing doubly labeled silylketene acetals indicates that the silyl-transfer step is intermol. Further mechanistic studies revealed a significant pos. nonlinear effect, proposed to arise from the selective formation of the [Cu((S,S)-Ph-pybox)((R,R)-Ph-pybox)](SbF6)2 2:1 ligand:metal complex. A stereochem. model is presented in which chelation of (benzyloxy)acetaldehyde to the metal center to form a square pyramidal copper intermediate accounts for the obsd. sense of induction. Support for this proposal has been obtained from double stereodifferentiating reactions, EPR spectroscopy, ESI spectrometry, and, ultimately, the X-ray crystal structure of the aldehyde bound to the catalyst. The C2-sym. bis(oxazolinyl)-Cu(II) complex [Cu((S,S)-tert-Bubox)](OTf)2 is also an efficient catalyst for the aldol reaction, but the scope with this system is not as broad. 30. Evans, D. A.; Burgey, C. S.; Kozlowski, M. C.; Tregay, S. W. Journal of the American Chemical Society 1999, 121, 686-699. 9 The C2-sym. (S,S)-tert-butyl-bis(oxazolinyl)Cu(OTf)2 complex (I) was shown to catalyze the enantioselective aldol reaction between a-keto esters and silyl ketene acetals or enol silanes with enantioselectivity ranging from 93 to 99%. With substituted silyl ketene acetals, syn reaction diastereoselection ranging from 90:10 to 98:2 and enantioselectivity ranging from 93 to 98% are obsd. High levels of carbonyl regioselectivity (98:2), diastereoselectivity (93:7), and enantioselectivity (97% ee) are also obsd. in the aldol addn. to 2,3-pentanedione. In all instances, the aldol adducts are generated in high yield and in excellent enantiomeric excess using as little as 1 mol % of the chiral complex I . Mechanistic insight into the pyruvate aldol reaction has also been gained. Silyl crossover expts. demonstrate that the silyl-transfer step is intermol. Based upon these results, TMSOTf was identified as an addend to accelerate these reactions. Furthermore, solvent was shown to have a dramatic impact on the rates of addn. and catalyst turnover in the pyruvate aldol reaction. Crystallog. structures and semiempirical calcns. provide insight into the mode of asym. induction, allowing the construction of a model in which chelation of the pyruvate ester through a square planar Cu(II) complex accounts for the obsd. sense of asym. induction. Two other Cu(II) complexes, [Cu((S,S)-isopropyl-pybox)](SbF6)2 and a bis(imine) complex, were also evaluated as enantioselective catalysts for the pyruvate aldol reaction; however, the scope of the process with these systems is more limited. 31. McCleland, B. W.; Nugent, W. A.; Finn, M. G. Journal of Organic Chemistry 1998, 63, 6656-6666. The mechanism of the enantioselective ring-opening of cyclohexene oxide by Me3SiN3, catalyzed by zirconium complexes of the C3-sym. ligand (+)-(S,S,S)-triisopropanolamine, has been investigated. Measurements of mol. wts. of precatalyst species show that complexes are formed with av. trimeric aggregation. Kinetics measurements reveal the overall process to be approx. half order in total zirconium, epoxide, and Me3SiN3 components. The reaction also shows a strong nonlinear relationship between enantiomeric excess of product azido ether vs. the incorporation of (R,S,S)-triisopropanolamine ligand in the catalyst mixt. On the basis of these and other results, a preequil. interconversion of dimeric and tetrameric zirconiumtriisopropanolamine species is proposed to occur rapidly with respect to the rate of epoxide ring-opening, with the dimeric form being the active catalyst. The reaction is accelerated by silyl ethers or by small amts. of water or alc., whereas larger amts. of protic additives inhibit the reaction. Enantioselectivity is eroded at catalyst concns. less than 1 mol-percent and at high concns. of cyclohexene oxide. Both enantioselectivity and rate are influenced to a small extent by the nature of the silyl azide employed for the first catalytic turnover, suggesting that a silyl fragment becomes irreversibly incorporated in the catalyst structure. It is proposed that catalytic activity requires the cooperative action of two zirconium centers for the binding and delivery of azide to epoxide. 32. Krueger, J.; Carreira, E. M. Journal of the American Chemical Society 1998, 120, 837-838. A new catalytic, enantioselective aldehyde addn. process is described which provides an efficient alternative to the well-established methods for conducting enantioselective Mukaiyama aldol addns. that have traditionally involved Lewis acid mediated addns. of O-silyl enolates and aldehydes. Importantly, this study demonstrates a new mechanistic model for the development of catalytic processes for aldehyde addn. reactions wherein enol silanes and chiral metal fluoride complexes are used to generate, in a catalytic fashion, metal enolates that undergo enantioselective aldol addn. reactions. Thus, treating a soln. of (S)-Tol-BINAP with Cu(OTf)2 and Bu4NSiPh3F2 produced a complex that effected the enantioselective addn. of silyl dienolate I to aldehydes RCHO (R = Ph, 2-naphthyl, 2-thienyl, 2-furyl, MeCH:CH, etc.) to give alcs. II. 10 Annotatated Bibliography of All References Before 1998 1. Takahashi, H.; Yoshioka, M.; Kobayashi, S. Yuki Gosei Kagaku Kyokaishi 1997, 55, 714-724. A review with 29 refs. In order to realize an efficient enantioselective reaction through a catalytic process, we were interested in modifying a Lewis acid by electron-withdrawing chiral ligands. In such a modified Lewis acid, the chiral ligand will not only provide a chiral environment,but also increase the acidity of Lewis acid. Among various electron-withdrawing groups we selected C2-sym. disulfonamide as a chiral ligand considering both electronic and steric characters. We developed (1) alkylation of aldehydes catalyzed by disulfonamide-Ti(O-iPr)4-dialkylzinc system, and (2) the 1st Simmons-Smith type cyclopropanation of allylic alcs. by Et2Zn-CH2I2-disulfonamide or Et2Zn-CH2I2-disulfonamide-Al system. The concept of modifying Lewis acid by electron-withdrawing chiral ligand will be helpful in developing other type of catalytic and enantioselective reactions. 2. Narasaka, K.; Hayashi, Y. Advances in Cycloaddition 1997, 4, 87-120. A review with 43 refs. of the scope and limitations of the Lewis acid catalyzed [2+2] cycloaddn. of vinyl and allenyl sulfides is presented. Following a discussion of reactions under thermal conditions, Lewis acid catalyzed reactions are presented with a particular focus on enantioselective processes. 3. Ishihara, K.; Gao, Q.; Yamamoto, H. Journal of the American Chemical Society 1993, 115, 1041213. The boron-substituent-dependent enantioselectivity of chiral tartaric acid-derived (acyloxy)borane (CAB) [I;R=1-hexynyl, PhC.tplbond.C,H,Me,Ph,3,5-(CF3)2C6H3,o-PhOC6H4,oNpOC6H4]-catalyzed asym. Diels-Alder reaction has been studied as a first step toward obtaining mechanistic information on the sp2-sp2 conformational preferences in a,b-enals where the possibility of s-cis or s-trans conformers exists in the transition-state assembly of Diels-Alder reaction catalyzed by Lewis acid. a-Substituted a,b-enal (methacrolein) favors s-trans conformation in the transition-state assembly independent of the steric feature of boronsubstituent. On the other hand, the sp2-sp2 conformational preference of a-nonsubstituted a,benals (acrolein and crotonaldehyde) are reversed by altering the structure of the boronsubstituent: s-trans conformation is preferred when the boron substituent is small (H, C.tplbond.CBu), while s-cis conformation is preferred when it is bulky (o-PhOC6H4). 4. Erker, G.; Schamberger, J.; van der Zeijden, A. A. H.; Dehnicke, S.; Krueger, C.; Goddard, R.; Nolte, M. Journal of Organometallic Chemistry 1993, 459, 107-15. 2-Bornenyllithium (3) was prepd. from camphor by a variant of the Shapiro reaction and then reacted with 0.5 molar equiv Et formate to give the dibornenylcarbinol I. Subsequent acidcatalyzed cyclization of I yielded \"dibornacyclopentadiene\" as a mixt. of two diastereoisomers; their deprotonation with n-butyllithium produced a single \"dibornacyclopentadienyllithium\" reagent II. Reaction of II with MCl4 (M = Zr, Hf, Ti) gave chiral organometallic Lewis-acids \"(diborna-Cp)MCl3\"; (+)-(dibornacyclopentadienyl)zirconium trichloride (III) was characterized by x-ray diffraction. 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