Synthesis of TRIP and Analysis of Phosphate Salt Impurities

Abstract

The chiral phosphoric acid TRIP, a useful Brønsted acid catalyst, easily becomes contaminated with metal impurities in the form of phosphate salts during synthesis. This significantly reduces the content of free acid in the product which can hamper the catalytic activity. Methods to easily judge whether TRIP contains mainly the free acid or phosphate salts are presented, using 1 H NMR spectroscopy or a simple pH test. An improved synthetic protocol for TRIP was established that reliably produces the free acid.In recent years, relatively strong chiral Brønsted acids have emerged as powerful catalysts for many asymmetric transformations. 1 Particularly effective are phosphoric acids 1 with an axially chiral binaphthyl backbone bearing sterically demanding substituents in the 3-positions, first introduced as catalysts by Akiyama and Terada 2 ( Figure 1). Among the many differently substituted binaphthyl-phosphoric acids, 3,3¢-bis(2,4,6-triisopropylphenyl)-1,1¢-binaphthyl-2,2¢-diyl hydrogenphosphate (2, abbreviated TRIP), emerged as a particularly powerful one in terms of activity and stereoselectivity. 3 Figure 1 Chiral binaphthyl phosphoric acids: general structure 1 and TRIP 2TRIP was first introduced for the asymmetric transfer hydrogenation of imines. 4 Other notable applications in which TRIP turned out to be the best asymmetric Brøn-sted acid catalyst include the reductive amination of abranched aldehydes, 5 an aldol conjugate reduction-reductive amination cascade, 6 Friedel-Crafts and PictetSpengler reactions 7 and cycloadditions. 8In the aforementioned reactions, asymmetry was introduced by the conjugate base of TRIP 2. The chiral phosphate can also effect stereoselectivity if employed in the form of salts in reactions with cationic intermediates, 9 a strategy also termed asymmetric counteranion directed catalysis (ACDC). 10 The TRIP anion has proven to induce high levels of stereoselectivity in combination with organic counterions, for example, in the transfer hydrogenation and epoxidation of a,b-unsatured aldehydes 10,11 and ketones, 12 respectively. The use of the TRIP anion in otherwise achiral transition-metal complexes enabled asymmetric gold-catalyzed allene cyclizations 13 and palladium-catalyzed allylic alkylations 14 with high levels of stereoselectivity. Furthermore, TRIP was also the catalyst of choice in combinations of Brønsted acid and transitionmetal catalysis. 15 Interestingly, alkali or alkaline earth salts of chiral phosphates 1 can also be efficient catalysts. 16 Feng and coworkers reported the use of sodium salts of 1 in an enantioselective Strecker reaction 16b and Ishihara and coworkers reported the use of alkali or alkaline earth salts for an enantioselective cyanosilylation of ketones 16a and a Mannich reaction. 16c In all these cases, the chiral induction was dependent on the metal counterion and the mode of preparation of the salts.Lately, Ishihara pointed out the possible salt formation and contamination of BINOL-derived phosphoric acids 1 during purification on silica gel and...

Development and Mechanism of an Enantioselective Bromocycloetherification Reaction via Lewis Base/Chiral Brønsted Acid Cooperative Catalysis

“…The pK a and general applicability of chiral phosphoric acids made them attractive candidates for the development of an enantioselective bromocycloetherification process using a catalytic amount of a chiral Brønsted acid, potentially in conjunction with a Lewis base co‐catalyst . This line of research led to the development of an enantioselective bromocycloetherification reaction of 5‐arylpentenols ( 1a , 1d , 1e , 1f , 1g , 1h , 1i , 1j , 1k , 1l , 1m ) cooperatively catalyzed by the combination of the versatile chiral phosphoric acid TRIP ( 2a ) and the achiral Lewis base Ph 3 P=S, producing chiral tetrahydrofurans ( 3a , 3d , 3e , 3f , 3g , 3h , 3i , 3j , 3k , 3l , 3m ) and tetrahydropyrans ( 4a , 4d , 4e , 4f , 4g , 4h , 4i , 4j , 4k , 4l , 4m ) (Fig. ) .…”

Enantioselective Bromocycloetherification by Lewis Base/Chiral Brønsted Acid Cooperative Catalysis

“…The pKa and general applicability of BINOL-derived phosphoric acids made them attractive candidates to initiate this study. 8 …”

Design and synthesis of new alkyl‐based chiral phosphoric acid catalysts

“…The synthetic route to PA 1 to 4 resembled the known synthesis of catalysts 1 . Starting from optically pure (R)‐BINOL 7 , the hydroxyl was protected by methyl groups, which could afford desired product 8 in high yield.…”

“…Different metal catalysts have been screened, and we found that Ni (PPh 3 ) 2 Cl 2 was suitable for Kumada cross‐coupling, and Pd (dppf)Cl 2 was compliant with the Suzuki coupling. Removal of the methyl groups with BBr 3 gave the compounds 11c and 11d . The phosphate group was introduced by reacting with POCl 3 , hydrolyzing with water and washing with 2 M HCl, which afforded pure PA 3 and PA 4 after recrystallization .…”