BINOL catalysis addition

The 2-pyrones can behave as dienes or dienophiles depending on the nature of their reaction partners. 3-Carbomethoxy-2-pyrone (84) underwent inverse Diels-Alder reaction with several vinylethers under lanthanide shift reagent-catalysis [84] (Equation 3.28). The use of strong traditional Lewis acids was precluded because of the sensitivity of the cycloadducts toward decarboxylation. It is noteworthy that whereas Yb(OTf)j does not catalyze the cycloaddition of 84 with enolethers, the addition of (R)-BINOL generates a new active ytterbium catalyst which promotes the reactions with a moderate to good level of enantio selection [85]. 

The LLB catalysts described above served an important role in demonstrating the proof of principle for catalysis with lanthanide-BINOL complexes. In addition, they were the first catalysts for the enantioselective nitroaldol reaction and gave respectable selectivities in synthetically useful yields. However, the reactions required at least 3.3 mol % of the catalysts for efficient conversion, and at that loading the reactions are rather slow. Clearly, the need for more effective catalysts is indicated. Consideration of the mechanism for the catalytic asymmetric... 

The possibility of using C-nucleophiles in chiral ion pair catalysis encouraged us to investigate an enantioselective Brpnsted acid catalyzed imino ene reaction (Rueping et al. 2007a Scheme 5). The reaction consists of a new BINOL-phosphate catalyzed addition of methylene-hydrazines 22 to A-Boc-protected aldimines 23 to afford chiral amino-hydrazones 24. 

Catalytic Michael additions of a-nitroesters 38 catalyzed by a BINOL (2,2 -dihydroxy-l,r-bi-naphthyl) complex were found to yield the addition products 39 as precursors for a-alkylated amino acids in good yields and with respectable enantioselectivities (8-80%) as shown in Scheme 9 [45]. Asymmetric PTC (phase transfer catalysis) mediated by TADDOL (40) as a chiral catalyst has been used to synthesize enantiomeri-cally enriched a-alkylated amino acids 41 (up to 82 % ee) [46], A similar strategy has been used to access a-amino acids in a stereoselective fashion [47], Using azlactones 42 as nucleophiles in the palladium catalyzed stereoselective allyla-tion addition, compounds 43 were obtained in high yields and almost enantiomerically pure (Scheme 9) [48]. The azlactones 43 can then be converted into the a-alkylated amino acids as shown in Scheme 4. 

These complexes are the first examples of multifunctional catalysts and demonstrate impressively the opportunities that can reside with the as yet hardly investigated bimetallic catalysis. The concept described here is not limited to lanthanides but has been further extended to main group metals such as gallium [31] or aluminum [32]. In addition, this work should be an incentive for the investigation of other metal-binaphthyl complexes to find out whether polynuclear species play a role in catalytic processes there as well. For example, the preparation of ti-tanium-BINOL complexes takes place in the presence of alkali metals [molecular sieve ( )]. A leading contribution in this direction has been made by Kaufmann et al, as early as 1990 [33], It was proven that the reaction of (5)-la with monobromoborane dimethyl sulfide leads exclusively to a binuclear, propeller-like borate compound. This compound was found to catalyze the Diels-Alder reaction of cyclopentadiene and methacrolein with excellent exo-stereoselectivity and enantioselectivity in accordance with the empirical rule for carbonyl compounds which has been presented earlier. 

Cyanosilylation. Another preparative procedure of BINOL-TiCl2 and the use thereof was reported in the asymmetric catalysis of the addition reaction of cyanotrimethylsilane to aldehydes. The dilithium salt of BINOL in ether was treated with... 

In our research on the asymmetric catalysis of the carbonyl-ene reaction, we found that the BINOL-Ti complexes (1) [30], prepared in situ, in the presence of 4-A molecular sieves, from diisopropoxytitanium dihalides (X2Ti(OPr )2 X = Br [31] or Cl [32]) and optically pure BiSfOL (vide infra), catalyze [33], rather than promote stoichiome-trically, the carbonyl addition reaction of allylic silanes and stannanes [34]. The addition to glyoxylate of ( )-2-butenylsilane and -stannane proceed smoothly to afford the syn product in high enantiomeric excess (Sch. 5). The s yn-product thus obtained could be readily converted to the iaetone portion of verrucaline A [35]. 

The Lewis acid-catalyzed conjugate addition of silyl enol ethers to a,y3-unsaturated carbonyl derivatives, the Mukaiyaraa Michael reaction, is known to be a mild, versatile method for carbon-cabon bond formation. Although the development of catalytic asymmetric variants of this process provides access to optically active 1,5-dicarbonyl synthons, few such applications have yet been reported [108], Mukiyama demonstrated asymmetric catalysis with BINOL-Ti oxide prepared from (/-Pr0)2Ti=0 and BINOL and obtained a 1,4-adduct in high % ee (Sch. 43) [109]. The enantioselectiv-ity was highly dependent on the ester substituent of the silyl enol ether employed. Thus the reaction of cyclopentenone with the sterically hindered silyl enol ether derived from 5-diphenylmethyl ethanethioate proceeds highly enantioselectively. Sco-lastico also reported that reactions promoted by TADDOL-derived titanium complexes gave the syn product exclusively, although with only moderate enantioselectiv-ity (Sch. 44) [110]. 

Oguni has reported asymmetric amplification [12] ((-i-)-NLE) in an asymmetric carbonyl addition reaction of dialkylzinc reagents catalyzed by chiral ami-noalcohols such as l-piperidino-3,3-dimethyl-2-butanol (PDB) (Eq. (7.1)) [13]. Noyori et al. have reported a highly efficient aminoalcohol catalyst, 2S)-3-exo-(dimethylamino)isobomeol (DAIB) [14] and a beautiful investigation of asymmetric amplification in view of the stability and lower catalytic activity of the het-ero-chiral dimer of the zinc aminoalcohol catalyst than the homo-chiral dimer (Fig. 7-5). We have reported a positive non-linear effect in a carbonyl-ene reaction [15] with glyoxylate catalyzed by binaphthol (binol)-derived chiral titanium complex (Eq. (7.2)) [10]. Bolm has also reported (-i-)-NLE in the 1,4-addition reaction of dialkylzinc by the catalysis of nickel complex with pyridyl alcohols [16]. 

Other fates are possible for the enolate formed in the initial conjugate addition and an obvious possibility is an aldol reaction. With an asymmetric catalyst, the combination of three simple molecules leads to one enantiomer of one diastereoisomer of the tandem Michael-aldol product14 83. The catalyst 84 is based on a BINOL A1 complex (see chapters 25, 26). It can be drawn either as a lithium salt with an aluminium cation or, better, as a lithium aryloxide with a Lewis-acidic aluminium atom. This is better because both basic ArCT and Lewis acidity are necessary for catalysis. 

Very recently, Fan et al. [13] reported on the use of a water-soluble PEO-substitut-ed first- and second-generation Frechet-type dendrimer with a chiral BINOL (1,1 -bi-2-naphthol) unit in catalysis. The enantiomeric excess in asymmetric hydrogenation of 2-[p-(2-methylpropyl)phenyl]acrylic acid with [RuCl(BINAP)(cymene)]Cl in an aqueous system was reported to increase upon addition of the dendritic... 

In 1992, Shibasaki et al. reported for the time an application of chiral heterobimetallic lanthanoid complexes (LnLB) as chiral catalysts in asymmetric catalysis, namely the catalytic asymmetric nitroaldol reaction (Henry reaction), which is one of the most classical C-C bond forming processes [11]. Additionally, this work represents the first enantioselective synthesis of (3-nitroalcohol compounds by the way of enantioselective addition of nitroalkanes to aldehydes in the presence of a chiral catalyst. The chiral BINOL based catalyst was prepared starting from anhydrous LaCl3 and an equimolar amount of the dialkali metal salt of BINOL in the presence of a small amount of water [9]. 

For example Hatano, M., Miyamoto, T. and Ishihara, K. (2005) Enantioselective addition of organozinc reagents to aldehydes catalyzed by 3,3 -bis(diphenylphosphinoyl)-BINOL. Advanced Synthesis and Catalysis, 347 1561-1568. 

The enamine catalysis detailed above proceeds via activation of the Mannich donor. An alternate strategy to the catalysis of the Mannich reaction is by the use of Brensted acids that activate the acceptor imine by protonation on nitrogen. Some of the most successful asymmetric variants of this process use BINOL-based phosphoric acids as catalysts. For instance Terada and coworkers used (7.144) to effect highly enantioselective addition of acetylacetone to a range of aryl aldimines ... 

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