QUINAP ligand

Asymmetric hydroboration of styrenes employing diphosphine complexes provides a successful solution to the generation of chirality at a benTyhc site, a potentially important route to many bioactive molecules. Since substitution on the double bond leads to severe loss of enantioselectivity, the apphcations are necessarily hmited. It was adventitiously discovered that the P,N-ligand QUINAP [47], which is effective in asymmetric... 

Using a related cycloaddition protocol, Schreiber found that the chiral P,N-ligand QUINAP (121) exhibited comparable high enantioselectivity in silver-catalyzed dipolar cycloadditions (Equation 6) [98], The highest asymmetric induction was observed for tert-hutyl acrylate (119) with aromatic imino esters such as 118. The process shows a wide substrate scope, as the transformation was tolerant both of a-substitution in 118 and of /3-substitution of the acrylate dipolarophile 119. Carreira has crafted and studied the use of a family of atropisomeric P,N-ligands, as exemplified by 122 [99]. 

The QUINAP ligands are highly active for reaction of -substituted vinylarenes, thus, p-methoxystyrene gives the corresponding branched alcohol in 95% yield (57% ee) within 15 min at room temperature. Similarly, a combination of hydroboration/amination using (13) has allowed primary amines to be formed in a one-pot reaction of vinylarenes upon reaction of the B H addition product with MeMgCl/H2N0S03H (Scheme 10).5°... 

The first successful axially chiral phosphinamine ligand in asymmetric catalysis was QUINAP 60 (Figure 8) reported by Brown in 1993 and the original synthesis has since been modified.94 The donor nitrogen atom is incorporated in an isoquinoline unit to form a six-membered chelate ring. 

PHENAP 65 was prepared and resolved98 in a similar manner to QUINAP 60 and tested in asymmetric rhodium-catalyzed hydroboration-oxidations." Impressive enantioselectivities were obtained and the sterically demanding cyclic substrates were hydroborated with 64-84% ee. Compared to the corresponding results obtained with diphosphine ligands, it is clear that QUINAP 60, and structural relatives 61-64 and PHENAP 65, give superior results in the asymmetric rhodium-catalyzed hydroboration of several vinylarenes, and are essentially the only practical solution for / -substituted alkenes.100 The reasons for this are not well understood, but thought to be due to the particular... 

In a new departure in the quest for QUINAP-type ligands with an electron-deficient phosphorus atom, a novel QUINAP-derived triarylphosphite ligand 73 (Figure 10) was developed by Brown 10 years after the parent ligand 60 was first reported.100... 

Ligand 73 was prepared directly from a single enantiomer of the corresponding naphthol of QUINAP 60, an early intermediate in the original synthesis, and both enantiomers of BINOL. Application in hydroboration found that, in practice, only one of the cationic rhodium complexes of the diastereomeric pair proved effective, (aA, A)-73. While (aA, A)-73 gave 68% ee for the hydroboration of styrene (70% yield), the diastereomer (aA, R)-73 afforded the product alcohol after oxidation with an attenuated 2% ee (55% yield) and the same trend was apparent in the hydroboration of electron-poor vinylarenes. Indeed, even with (aA, A)-73, the asymmetries induced were very modest (31-51% ee). The hydroboration pre-catalyst was examined in the presence of catecholborane 1 at low temperatures and binuclear reactive intermediates were identified. However, when similar experiments were conducted with QUINAP 60, no intermediates of the same structural type were found.100... 

Cationic rhodium complexes of these ligands were prepared and applied in the enantioselective hydroboration-oxidation of a range of vinylarenes,106,107 carefully chosen to highlight the effect on reactivity and enantioselectivity of different aryl substituents and / -substitution. Like QUINAP 60 and PHENAP 65, the ( -ligand gave rise to the (A)-secondary alcohol. 

CuBr/QUINAP System The CuBr/QUlNAP system was initially used in the enan-tioselective synthesis of proparyl amines via the reaction of alkynes and enamines (Scheme 5.5). It was rationalized that the enamines reacted with protons in terminal alkynes in the presence of copper catalyst to form zwitterionic intermediates in which both the generated iminiums and alkyne anions coordinate to the copper metal center. After an intermolecular transfer of the alkyne moiety to the iminium ion, the desired products were released and the catalyst was regenerated. The combination of CuBr as catalyst and the chiral ligand QUEMAP is crucial for the good reactivities and enantioselectivities seen in the reaction. Another potential... 

Although the CuBr/QUINAP system is an effective chiral catalyst in alkynylation of imines or iminiums, one drawback is that enantiopure QUINAP is quite expensive. An analog of QUINAP, PINAP (Figure 5.2), was readily synthesized and found as a very effective chiral ligand in the direct addition of alkynes to iminiums generated from aldehydes and secondary amines in situ (Scheme 5.8). ... 

Fig. 2.9 Template structures for the intermediate in catalytic asymmetric hydroboration with alkene, ligand, catechoborane and hydride coordinated, (a) R-BINAP and (b) R-QUINAP. E-propenylbenzene is illustrated to show the increased steric hindrance to the alkene in the BINAP case.

The rhodium-catalysed reaction between simple alkenes (50) and bis(catecholato) diboron (51) has been reported to result in the syn addition of the diboron across the alkene. The l,2-bis(boronate) thus obtained was subsequently oxidized to provide the corresponding 1,2-diol (52). In the presence of QUINAP ligand, high enantioselection in the diboration was attained. The reaction was found to be highly selective for trans- and trisubstituted alkenes and can also be selective for some monosubstituted alkenes.59... 

A copper-catalysed, enantioselective, conjugate addition of a terminal alkyne, which undergoes an in situ metallation, has been reported. The addition of phenylacetylene to Meldrum s acid-derived acceptors (196) takes place in aqueous medium, without recourse to an inert atmosphere. The success of the enantioselective reaction was made possible by the use of PINAP (198), a new class of P,IV-ligands (cf. QUINAP), which have the advantage of easier resolution. Furthermore, these modular ligands are responsive to numerous electronic and steric modifications that permit optimization of the reaction. The products (197) were obtained in good yields and with 82-97% ee.235... 

While Quinap (95) is an excellent and versatile ligand from which numerous developments in asymmetric catalysis have benefited,49 its synthesis is cumbersome, and hence its price remains high (R enantiomer 100 mg, 337 CHF). Carreira et al. showed that the synthetically readily accessible PEMAP ligand class is as versatile as... 

Quinap (95) in a number of mutually unrelated transition-metal-catalyzed asymmetric reactions.50 Thus, 105 added to tert-butyl acrylate 106 using silver acetate and PINAP ligand 96, under the conditions described in Scheme 2.25, to provide the desired product 109 in excellent enantioselectivity and yield (see Scheme 2.6 and Table 2.5). Notably, the reaction required only 3 mol% of catalyst for complete conversion at -40°C within 36 h. 

Asymmetric reaction is one of the most exciting features of catalyzed hydroboration since optically active phosphine ligands are the chiral auxiliaries most extensively studied for metal-catalyzed reactions (Scheme 13).134 The chiral ligands used for asymmetric hydroboration of alkenes include BINAP,136 1 03-106,167-170 QUINAP,171-173 107-109,172,174-176 and BDPP.177,178... 

Another heterobidentate chiral ligand that has been used with success in catalysis is the phosphine QUINAP , 90. It is prepared using a palladium-catalysed coupling procedure, followed by a resolution of the racemic product using a chiral palladium salt (Scheme 32).58... 

Li and co-workers examined a variety of ligands such as chiral bisoxazolines, Quinap, and Binap as ligands in conjugation with various copper salts. Li found that CuOTf with PyBox provided the best results for 29 and found that aromatic substituted alkynes gave the best yields and enantioselectivity relative to the aliphatic substituted alkynes. Li also found that the presence of an ort/io-methoxy substituent improved enantioselectivity and attributed the improvement in selectivity to potential coordination of the oxygen atom to the copper/Ugand complex. 

Pyridines have also been constructed as essential portion of ligands used for transition metal catalysis. Chan and co-workers report the synthesis of dipyridylphosphines as ligands for the Ru-catalyzed asymmetric hydrogenation of p-ketoesters <01SL1050>. Pallet and coworkers report on the synthesis and use of a Ruthenium (R)-QUINAP catalyst for use in enantioselective Diels-Alder reactions <01OM2454>. 

---