Two BINOL

Complexes of other metals such as gallium, indium, lead, and antimony have also been used as Lewis acids. Catalytic enantioselective meso-epoxide ring-opening reactions using a chiral gallium(III) catalyst (Ga-Li-linked-BINOL) have been reported (Scheme 84).348 The chemical yields are much improved by linking two BINOL units. 

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. 

In 2008, Gong and coworkers introduced a new chiral bisphosphoric acid 19 (Fig. 4) that consists of two BINOL phosphates linked by an oxygen atom for a three-component 1,3-dipolar cycloaddition (Scheme 42) [66]. Aldehydes 40 reacted with a-amino esters 105 and maleates 106 in the presence of Brpnsted acid 19 (10 mol%) to afford pyrrolidines 107 as endo-diastereomers in high yields (67-97%) and enantioselectivities (76-99% ee). This protocol tolerated aromatic, a,P-unsaturated, and aliphatic aldehydes. Aminomalonates as well as phenylglycine esters could be employed as dipolarophiles. 

In 1997 Pu reported a new type of main chain chiral polymer derived from BINOLs [24]. Polymer 16 catalyzed enantioselective ethylation using diethylzinc to give secondary alcohols in up to 94% ee. It is noteworthy that 16 is a derivative of chiral BINOL but the addition of Ti(IV) is unnecessary unlike other reported chiral monomeric diols. In 1998, Pu reported that polymer 17, which has a phenylene spacer between two BINOL moieties, results in better ees of up to 98% [24]. 

Shibasaki made several improvements in the asymmetric Michael addition reaction using the previously developed BINOL-based (R)-ALB, (R)-6, and (R)-LPB, (R)-7 [1]. The former is prepared from (R)-BINOL, diisobutylaluminum hydride, and butyllithium, while the latter is from (R)-BINOL, La(Oz -Pr)3, and potassium f-butoxide. Only 0.1 mol % of (R)-6 and 0.09 mol % of potassium f-butoxide were needed to catalyze the addition of dimethyl malonate to 2-cy-clohexenone on a kilogram scale in >99% ee, when 4-A molecular sieves were added [15,16]. (R)-6 in the presence of sodium f-butoxide catalyzes the asymmetric 1,4-addition of the Horner-Wadsworth-Emmons reagent [17]. (R)-7 catalyzes the addition of nitromethane to chalcone [18]. Feringa prepared another aluminum complex from BINOL and lithium aluminum hydride and used this in the addition of nitroacetate to methyl vinyl ketone [19]. Later, Shibasaki developed a linked lanthanum reagent (R,R)-8 for the same asymmetric addition, in which two BINOLs were connected at the 3-positions with a 2-oxapropylene... 

A similar bidentate ligand containing a ferrocenyl bridge between two BINOL moieties was described by Reetz and co-workers. Copper-catalyzed 1,4-addition reactions of diethylzinc to cyclohex-2-enone and cyclohept-2-enone in... 

Hydrogenation. For an effective asymmetric hydrogenation of itaconic esters, the heterocomplex with Rh(I) center associated with two BINOL-derived phosphites of opposite electron-richness (lA, IB) emerges as a more active and selective catalyst. Also having been examined are 2 and the one bearing a carboranyl residue. ... 

Maruoka reported that 2,2 -bis(tritylamino)-4,4 -dichlorobenzophenone can be used as a bridge to combine two BINOL-Ti complexes together. This kind of... 

As shown in Equation 13, enantioselective Strecker reaction was catalyzed by the BINOL dinuclear zirconium catalyst (40) [18]. Interestingly, the combination of two BINOL (3,3 -Br2BlNOL and 6,6 -Br2BlNOL) was found to be very important to achieve high enantioselectivity. From the NMR analyses, structure (40) was suggested. 

Based on this synthetic strategy, three imidodiphosphoric acids 13-15 with bulky substituents on the 3,3 -positions of the two BINOL backbones were reported (Scheme 26) [57]. 

The crystal structure of imidodiphosphoric acid 13 revealed a confined active site placed within a extremely sterically demanding chiral environment (Fig. 1). Top view at the catalytic moiety shows how the two BINOL substituents surround the active site (Fig. lb). From the bottom half, two remaining BINOL subunits completely block access to the imidodiphosphate (Fig. Ic) [57]. 

One of these approaches used a heterobimetallic catalyst consisting of two BINOL fragments attached to an aluminum center along with a lithium counterion (Scheme 4.145) [235]. Secondary phosphites were used as the phosphorus nucleophiles, and a wide range of aldehydes were readily functionalized using this approach. While moderate to high enantioselectivities were observed using arylaldehydes as substrates, aliphatic aldehydes were considerably less selective (ee s=3-24%). 

The assumed transition state of this reaction is shown in Scheme 5.3. Yb(OTf)3, (J )-(-h)-BINOL, and DBU form a complex with two hydrogen bonds, and the axial chirality of (J )-(-h)-BINOL is transferred via the hydrogen bonds to the amine parts. The additive would interact with the phenolic hydrogen of the imine, which is fixed by bidentate coordination to Yb(III). Because the top face of the imine is shielded by the amine, the dienophiles approach from the bottom face to achieve high levels of selectivity. 

The stereoselective synthesis of hexacoordinated phosphate anions was also reported by the same group. A general one-pot process was developed for the preparation of C2-symmetric anions 15,16 and 17 containing enantiopure BINOL, hydrobenzoin, and tartrate-derived ligands respectively [38-40] Cpsymmetric anion 18 being prepared similarly in two steps from methyl-a-... 

Over the last few years several examples have been reported in the field of asymmetric catalysis that are based on the interaction of two centers.6,119 Recently, Shibasaki and coworkers have developed an asymmetric two-center catalyst. Scheme 3.14 shows preparation of optically active La binaphthol (BINOL). This catalyst is effective in inducing the asymmetric nitro-aldol reaction, as shown in Scheme 3.15. 

Two reports have been made of the preparation of P-chiral phosphine oxides through reaction of chiral f-butylphenylphosphine oxide treated with LDA and electrophiles. The electrophiles included aldehydes,355 ketones,355 and benzylic-type halides.356 Optically active a-hydroxyphosphonate products have also been generated from aldehydes and dialkyl phosphites using an asymmetric induction approach with LiAl-BINOL.357... 

Although disubstituted alkynes are used successfully as two-carbon components in chromium-mediated and -catalyzed [6 + 2]-reactions, the use of terminal alkynes produces a [6 + 2 + 2]-reaction (Section 10.13.3.7). Buono and co-workers have discovered that when a cobalt catalyst is employed, several monosubstituted alkynes can be used in [6 + 2]-cycloadditions with cycloheptatriene (Scheme 35). The use of a chiral BINOL-phosphoramidite cobalt complex affords an enantioselective [6 + 2]-cycloaddition reaction (Equation (18)).121... 

Zhang reported two new (S)-BINOL based ligands phosphine-phosphite (S,R)-o-BINAPHOS 163 and phosphine-phosphinite (S)-o-BIPNITE 164 [128]. Applications of these ligands in the Rh-catalyzed hydrogenation of methyl N-2-acetamido-cinnamate and methyl N-2-acetamidoacrylate induced very high enantioselectiv-ities (>99% ee), and with a wide range of substrates. 

The self-assembly of a chiral Ti catalyst can be achieved by using the achiral precursor Ti(OPr )4 and two different chiral diol components, (R)-BINOL and (R,R)-TADDOL, in a molar ratio of 1 1 1. The components of less basic (R)-BINOL and the relatively more basic (R,R)-TADDOL assemble with Ti(OPr )4 in a molar ratio of 1 1 1, yielding chiral titanium catalyst 118 in the reaction system. In the asymmetric catalysis of the carbonyl-ene reaction, 118 is not only the most enantioselective catalyst but also the most stable and the exclusively formed species in the reaction system. 

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. 

However, the two methods of choice for the oxidations of a, (B-unsaturated ketones are based on lanthanoid-BINOL complexes or a biomimetic process based on the use of polyamino acids as catalysts for the oxidation 1"1. 

The presence of two chiral units in ligand 18 results in a matched (S, R, R) and a mismatched (S, S, S) combination. The absolute stereochemistry of the product is controlled by the BINOL moiety and the amine component has a distinct effect in... 

Pfaltz introduced phosphite ligands 22, with BINOL and chiral oxazoline units, which gives excellent enantioselectivities [47]. In phosphoramidites 14 and 15 (Scheme 7.9) the structure of the amine moiety is crucial, but substituents at the 3,3 -positions of the BINOL unit had only minor influences on the enantiose-lectivity of the 1,4-addition to cyclohexenone. In contrast, the introduction of the two 3,3 -methyl substituents in ligand 22 increased the ee drastically from 54% to 90%. 

Concurrent with studies on cyclometalation, studies on the effects of the structure of phosphoramidite ligand had been conducted. Several groups studied the effect of the stmcmre of ligand on the rate and selectivity of these iridium-catalyzed allylic substitutions. LI contains three separate chiral components - the two phenethyl moieties on the amine as well as the axially chiral BINOL backbone. These portions of the catalyst structure can control reaction rates by affecting the rate of cyclometalation, by inhibiting catalyst decomposition, or by forming a complex that reacts faster in the mmover-limiting step(s) of the catalytic cycle. 

---