Zr-BINOL complex

Allylation. 4-t-Butylcalix[4]arene activates the Zr-BINOL complex in the allylation... 

A direct asymmetric aldol reaction of diazoester was catalyzed by the Zr-BINOL catalyst system (Equation 17) [22]. Although the enantioselectivity was moderate, it is worth noting that the Zr-BINOL complex realized the aldol reaction of nonactivated substrates under catalytic conditions in an enantioselective manner. 

Several types of Zr-catalyzed asymmetric allylation of carbonyl compounds with allylstannanes were reported [38] as shown below. In all cases, Zr-BINOL complexes were used as a catalyst along with additives such as phenolic ketone (74) (Equations 33 and 34), [39] pivalonitrile (Equation 35), [40] and MeOH (Equation 36) [41]. 

The Zr-BINOL complexes were effectively utilized for asymmetric aza- and hetero Diels-Alder reactions [lb]. The reaction of imine (27) with Danishefsky diene (113) afforded optically active dihydropyridone (114) in high yield (Equation 52) [7, 57]. A similar reaction was also possible for benzaldehyde and diene (115) (Equation 53), [7, 58] and the corresponding dihydropyranone was obtained in excellent yield with excellent enantioselectivity. In addition, the reaction was applied for total synthesis of natural products [58b]. 

An asymmetric [2 + 3] cycloaddition reaction was performed with the Zr-BINOL complex (Equation 58) [62]. N-(p-Nitrobenzoyl)hydrazone (132) was effectively... 

Kobayashi and co-workers. used zirconium-based bromo-BINOL complex for the catalytic enantioselective Mannich-type reaction. The o-hydroxyphenyl imine 3.36 chelates the Zr(IV)(BrBINOL)2 to form the activated chiral Lewis acid complex A. The ketone acetal 3.37 reacts with the Lewis acid complex A to give the complex B. The silyl group is then transferred to the 3-amino ester to form the product 3.38 and the catalyst Zr(BrBINOL)2 is regenerated, which is ready for binding with another imine molecule (Scheme 3.16). 

S)-Zr(EBTHI) complex. Thus, the recently developed procedure of Buchwald [22] is used to resolve rac-(EBTHI)Zr to obtain (R)-Zr(EBTHI)-binol and (S)-Zr(EBTHI)-biphen to accomplish this total synthesis in an efficient manner. 

Kinetic resolution Cyclic allylic ethers react with EtMgBr in the presence of a zirconocene-BINOL complex [(/ HEBTHI)Zr-BINOL], showing enantioselectivity. Thus, unreacted ethers are recovered in the chiral form. 

Kobayashi has reported a remarkable series of chiral Zr(IV) complexes as catalysts for enantioselective aldol addition reactions [136, 137]. These are readily prepared from 3,3 -dihalo-BINOL derivatives and Zr(OtBu)4. The putative zirconium complex 266 is reported to mediate the formation of anti aldol adducts with excellent diastereo- and enantioselectivity (Scheme 4.33). It is noteworthy that under optimal conditions, the reactions are carried out in aqueous propanol/toluene solvent mixtures. As such, the process is tolerant of and indeed thrives in, the presence of water. A demonstration of its use was reported in the synthesis of khafrefungin (269), an inhibitor of fungal sphingolipid synthesis [137]. 

Ti-BINOL-catalyzed reactions have been well established. When the Ti is replaced by Zr,92 the resulting complex 140 can also catalyze the addition of allyl-tributyltin to aldehydes (aldehydes allyl-tributyltin 140 = 1 2 0.2 mol ratio) in the presence of 4 A MS. Product l-alken-4-ols are obtained in good yield and high ee. The, Sz-face of the aldehyde is attacked if (S)-BINOL is used, and Re-face attack takes place when (K)-BINOL is used as the chiral ligand. For Zr complex-catalyzed reactions, the reaction proceeds much faster, although the... 

Catalytic asymmetric cyanide addition to imines constitutes an important C—C bondforming reaction, as the product amino nitriles may be converted to non-proteogenic a-amino acids. Kobayashi and co-workers have developed two different versions of the Zr-catalyzed amino nitrile synthesis [73]. The first variant is summarized in Scheme 6.22. The bimetallic complex 65, formed from two molecules of 6-Br-binol and one molecule of 2-Br-binol in the presence of two molecules of Zr(OtBu)4 and N-methylimidazole, was proposed as the active catalytic species. This hypothesis was based on various NMR studies more rigorous kinetic data are not as yet available. Nonetheless, as depicted in Scheme 6.22, reaction of o-hydroxyl imine 66 with 5 mol% 65 and 1—1.5 equiv. Bu3SnCN (CH2C12, —45 °C) leads to the formation of amino nitrile 67 with 91 % ee and in 92 % isolated yield. As is also shown in Scheme 6.22, electron-withdrawing (— 68) and electron-rich (—> 69), as well as more sterically hindered aryl substituents (— 70) readily undergo asymmetric cyanide addition. 

Kobayashi and his team have utilized a catalytic system similar to that used in their development of a Zr-catalyzed Mannich reaction (Schemes 6.27—6.29) to develop a related cycloaddition process involving the same imine substrates as used previously (Scheme 6.35) [105]. As the representative examples in Scheme 6.35 demonstrate, good yields and enantioselectivities (up to 90% ee) are achieved. Both a less substituted version of the Danishefsky diene (—> 110) and those that bear an additional Me group (e. g.— 111) can be utilized. Also as before, these workers propose complex 89, bearing two binol units, to be the active catalytic species. 

The effectiveness of various substituted BINOL ligands 12-16 in the Zr(IV)-or Ti(IV)-catalyzed enantioselective addition of allyltributyltin to aldehydes was also investigated by Spada and Umani-Ronchi [21], The number of noteworthy examples of asymmetric allylation of carbonyl compounds utilizing optically active catalysts of late transition metal complexes has increased since 1999. Chiral bis(oxazolinyl)phenyl rhodium(III) complex 17, developed by Mo-toyama and Nishiyama, is an air-stable and water-tolerant asymmetric Lewis acid catalyst [23,24]. Condensation of allylic stannanes with aldehydes under the influence of this catalyst results in formation of nonracemic allylated adducts with up to 80% ee (Scheme 3). In the case of the 2-butenyl addition reac-... 

Several other chiral Lewis acids have been developed for the addition of allyl and methallyl tributylin to aldehydes [28]. These additions usually proceed slowly with reaction times of days. Less reactive stannanes, for example crotyl tributyltin, require even longer times and diastereoselectivity is poor. The allyl and methallyl additions, however, afford products in high yield and ee. The most successful ligands are BINOL and BINAP as Ti or Zr complexes in the former case and an AgOTf complex in the latter. 

Somewhat better results with this eatalyst system are obtained in additions of allyl tributyltin to aldehydes (Table 18) [32]. Although it is also possible to catalyze the same additions with a (P)-BINOL Zr(0-/-Pr)2 complex [33], the yields and ee of the adducts are generally lower. 

When catalytic asymmetric allylation was attempted with a catalytic amount of chiral titanium complexes, BINOL-TiCl2 or BIN0L-Ti(0-/-Pr)2 the reaction was found to be slow. The reaction was performed satisfactorily when BIN0L-Zr(0-/-Pr)2 was employed as catalyst in the presence of molecular sieves (Eq. 18) [19a]. 

Addition to imines. Effective synthesis of a-aminonitriles and of 3-amino acid derivatives from imines calls for the use of a Zr complex of 6,6 -dibromo-BINOL. Products containing an oxygen functionality at the a-position are similarly accessible, the diastereoselectivity of such a reaction can be controlled by choosing the proper a-alkoxy substituent in the nucleophiles. The TBSO substituent favors syn products whereas BnO derivatives give anti products selectively. 

In the presence of a Zr complex of (J )-6,6 -dibromo-BINOL, A -(2-hydroxyphenyl)-aldimines participate in asymmetric hetero-Diels-Alder reactions It is an improvement to the reactions involving stoichiometric chiral boron reagents. 

The catalyzed hydrocyanation of imines (Strecker reaction) has the option of employing a stable (salen)aluminum chloride or a Zr complex of 6,6 -dibromo-BINOL, with BujSnCN. It is important to derive the imines firom o-aminophenol for the present purpose. 

Chiral an a-metallocene complexes have become useful catalysts in asymmetric polymerization reactions [73]. While enantio-resolution of a <3-metaIlocene race-mates cannot yield more than 50% of a particular enantiomer, the readily accessible racemate of a biphenyl-bridged metallocene complex (we abbreviate to bi-phecp -M M = Ti, Zr) has been quite recently reported to give enantio-pure ansa-titanocene and -zirconocene complexes through binol-induced asymmetric trans-... 

To address the design criteria listed above, Kobayashi and co-workers prepared the mildly Lewis acidic zirconium[BINOL]2 complexes 78a,b from Zr(Of-Bu)4and (i )-BINOL and theimines 76 derived from 2-aminophenol [51a, 51b, 51c, 51d] (Scheme 26). In the presence of catalytic amounts of 78a the tri-methylsilyl ketene acetal of methyl 2-methylpropanoate (77) reacted with 76a to afford the adduct 79 quantitatively and with 34% ee. The use of N-methylim-idazole (NMI) in equal amoimts markedly improved the selectivity to 70% ee as did the use of 78b which provided 79 in 90% ee. By chemical correlation the products were shown to be of the i -configuration. The reaction displayed some generality with aromatic aldimines (83-98% ee), but the one enoHzable aldi-mine gave only modest results (56% yield, 80% ee) [51e]. 

Tagliavini and Umani-Ronchi found that chiral BINOL-Zr complex 9 as well as the BINOL-Ti complexes can catalyze the asymmetric allylation of aldehydes with allylic stannanes (Scheme 9) [27]. The chiral Zr catalyst 9 is prepared from (S)-BINOL and commercially available Zr(0 Pr)4 Pr0H. The reaction rate of the catalytic system is high in comparison with that of the BINOL-Ti catalyst 4, however, the Zr-catalyzed allylation reaction is sometimes accompanied by an undesired Meerwein-Ponndorf-Verley type reduction of aldehydes. The Zr complex 9 is appropriate for aromatic aldehydes to obtain high enantiomeric excess, while the Ti complex 4 is favored for aUphatic aldehydes. A chiral amplification phenomenon has, to a small extent, been observed for the chiral Zr complex-catalyzed allylation reaction of benzaldehyde. 

Aldolreaction. A catalytic asymmetric version using a Zr complex of 3,3 -diiodo-BINOL has been developed. 

ZnX2," " ZnCl2," ° Zn(0Tf)2-H20," ZnF2 with diamine complex,- Et2Zn with (S, S) linked BINOL,dinuclear zinc catalyst," chiral zirconium catalyst" (e.g., Zr(0-... 

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