BINOL-based phosphoric acid catalyst

Examining a variety of chiral BINOL based phosphoric acid catalysts in 2005, List found TRIP (Scheme 7.4) to be optimal (1.0mol%) for the catalytic protonation of preformed imines of p anisidine [15]. 

Concurrently, the group of Akiyama reported the use of the rather similar (/ )-BINOL-based phosphoric acid catalyst 76g [48]. A selection of aldimines 78a-d was reacted with silyl ketene acetals 79a-b to give rise to the p-amino esters 8 a-d in good dr (>86 14 iyn-selectivity) and high ee (np to 96%, Scheme 5.37). 

Gong s group reported the first catalytic enantioselective Biginelli-like reaction [46, 47] using cyclic and acyclic ketones (33 and 35, respectively), instead of p-ketoester and a BINOL-based phosphoric acid catalyst 34 (Scheme 9.10 and Fig. 9.2). 

The vinylogous Mannich reaction of 2 silyloxy furans and imines may also be catalyzed through chiral Brpnsted acids, as shown by Akiyama et al. [10]. Previously, Akiyama [11] and Terada [12] had independently discovered that 3,3 substituted BINOL based phosphoric acids were excellent Bronsted acids for a broad range of mainly imine addition reactions via protonation of the imines and in situ formation of chiral iminium contact ion pairs. Using the slightly modified phosphoric acid 28 as catalyst carrying additional iodine substituents in the 6,6 positions, the y amino substituted butenolides 27 were obtained in excellent enantioselectivity and variable diastereoselectivity (Table 5.4). 

The TBS group was chosen as silyl fragment within the dienolate to prevent a attack of the imines on the nucleophile. As chiral catalyst we employed a BINOL based phosphoric acid of the same type that Akiyama and Terada had established in asymmetric catalysis and found 3,3 mesityl groups optimal for the enantioselectivity of the reaction. The reactions were run at 30 °C in a solvent mixture of fBuOH, 2 methyl 2 butanol,andTHFin equal amounts containing anadditionallequivofwater. 

The enamine catalysis detailed above proceeds via activation of the Mannich donor. An alternate strategy to the catalysis of the Mannich reaction is by the use of Brensted acids that activate the acceptor imine by protonation on nitrogen. Some of the most successful asymmetric variants of this process use BINOL-based phosphoric acids as catalysts. For instance Terada and coworkers used (7.144) to effect highly enantioselective addition of acetylacetone to a range of aryl aldimines ... 

Recently reported asymmetric synthesis of thiols (e.g.. Scheme 3.7f employing chiral BINOL-based phosphoric acids as a catalyst was studied... 

In 2008, Du and coworkers designed and synthesized novel double axially chiral phosphoric acid catalysts based on BINOL [28]. Subsequently, these catalysts have been successfully applied in asymmetric transfer hydrogenation of 2 substitued (Table 10.8) and 2,3 disubstitued quinolines (Scheme 10.26). They found that ether was the best solvent. For 2 substitued quinolines, up to 98% ee was obtained when the substitutent of catalyst was cyclohexanyl. 

Therefore an efficient substrate recognition site could be constructed around the activation site of the phosphoric acid catalyst, namely the acidic proton, as a result of the acid/base dual function and stereoelectronic influence of the substituents (STG). The BINOL derivatives were selected as chiral sources to construct the ring structure The C2 symmetry is crucial in the catalytic design because it means that the same catalyst molecule is generated when the acidic proton migrates to the phosphoryl oxygen. In addition, both enantiomers of the binaphthols are commercially available [52]. 

Spirocyclic phosphoric acid catalyst STRIP (6) turned out to be crucial in the development of the kinetic resolution of homoaldols. The SPINOL backbone outperformed a variety of other previously described phosphoric acids based on BINOL (3 and 2), H8-B1NOL (9), VAPOL (1), and TADDOL (10) backbones (Table 2). 

The Mukaiyama aldol reaction is beyond doubt a brilliant triumph of modem synthetic organic chemistry however, the reaction products are contaminated with pre-activated silyl enol ethers derived from the carbonyl compounds with stoichiometric amounts of silylation agent and base. In addition, silylated wastes are inherently formed. Circumventing the pre-activation process improves atom efH-ciency in this case, the carbonyl nucleophiles react directly with the carbonyl electrophiles in the presence of catalyst. The first Bronsted acid-catalyzed direct aldol reactions have been achieved using chiral Hg-BINOL-derived phosphoric acid 96 (Scheme 28.12) [66], The aldol products (127) have syn-configurations and, thus, this reaction is complementary to (S)-proHne catalysis in Brpnsted acids, which in general yields the anti configuration [11]. 

At the same time, however, the iridium-catalyzed hydrogenation of 80 was reported using chiral phosphoric acid diester 17be based on BINOL [47a]. Full conversion and a maximum e.e. of 50% was observed, again in a slow reaction. Interestingly, a catalyst based on palladium and 17be afforded 39% e.e. and full conversion in the hydrogenation of aryl imine 87. 

In 2006, Yamamoto and Nakashima picked np on this and designed a chiral A -triflyl phosphoramide as a stronger Brpnsted acid catalyst than the phosphoric acids based on this concept. In their seminal report, they disclosed the preparation of new chiral BINOL-derived A -triflyl phosphoramides and their application to the asymmetric Diels-Alder (DA) reaction of a,p-unsaturated ketones with sily-loxydienes [83], As depicted in Scheme 59, chiral A-triflyl phosphoramides of the general type 4 are readily synthesized from the corresponding optically active 3,3 -substituted BINOL derivatives 142 through a phosphorylation/amidation route. 

Direct diastereo- and enantioselective hydrohydroxyalkylations of butadiene, an abundant petrochemical feedstock, required the use of a mthenium catalyst modified by a chiral phosphate counterion derived from Hg-BINOL. The anion is attached to the metal center through the acid-base reaction of H2Ru(CO)(PPh3)3 with the indicated chiral phosphoric acid. With the chiral counterion as the sole chiral inducing element, primary benzylic alcohols hydrohydroxyalkylate butadiene with good levels of anri-diastereo- and enantioselectivity (Scheme 3) [37]. 

Chiral phosphoric acids as metal-free Bronsted acid catalysts possess tremendous potential application in asymmetric synthesis. The Hg-BINOL-based... 

In the second reaction, a Michael-Michael cascade between an unsaturated oxin-doles 17 and enones 22 was shown to be catalyzed by a primary amine-derived catalyst (II) (Scheme 10.3). The reaction afforded the spirooxindoles 23 in excellent yields and diastereo and enantioselectivities. Wang used a similar approach in the reaction of isatylidene malononitriles and enones [12]. The reaction was catalyzed by the dual combination of cinchona-based chiral primary amine and BINOL phosphoric acids to afford the spirocycles in excellent yields (88-99%), diastereo (up to 99 1 dr), and enantioselectivities (95-99% ee). 

In general, bulky substituents at the 3,3 -position of the BINOL backbone are required to achieve good selectivities in asymmetric catalysis. This laborious catalyst fine-tuning can be simplified when chiral l,r-binaphthyI-2,2 -disulfonic acid (BINSA, 141) is used instead of the aforementioned BINOL-derived chiral phosphoric acids. Complexation with a suitable achiral amine enables to tune the bulkiness and Brpnsted acidity in situ [98]. Based on this approach, Ishihara and coworkers combined various A-Boc- or A-Cbz-protected imines and acetyl acetone in the presence of BINS A (1 mol%) and 2,6-diphenylpyridine (142, 2mol%) to afford the corresponding Mannich products in excellent yields and enantioselectivities (Scheme 11.31) [98]. However, the cata-... 

---