Asymmetric QUINAP ligand

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... 

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.

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... 

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... 

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>. 

The author expected that a reaction with a chiral ligand which coordinates to a copper atom could produce optically active 2-(aminomethyl)indoles. Knochel recently developed a novel asymmetric synthesis of chiral propargylamines with excellent ee values through a copper-catalyzed asymmetric Mannich-type reaction of alkynes with an aldehyde and a secondary amine using QUINAP as a chiral ligand (up to 98% ee) [1-3]. Carreira reported the similar synthesis of propargylic amine in up to 99% ee with PINAP [4, 5]. The author initially examined the... 

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]. 

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