Chiral BINOL-phosphoric acid catalyst

A related reaction involves the use of aryl indole-3-carbinols with enamides. Under the influence of acid catalysts the carbinols generate electrophiles. The adducts hydrolyze to products that are the equivalent of conjugate addition to 1,3-diaryl propenones. These reactions can be done in up to 90% ee with chiral BINOL-phosphoric acid catalysts [293]. 

The good enantio- and regioselectivity can be explained through transition state TS-6 where the azomethine ylide and the methyleneindolinone build hydrogen bonds with the chiral BINOL-phosphoric acid catalyst 239 (Fig. 6.10). 

Enantioselective versions of the Hantzsch reaction have also been reported. As shown in Scheme 3.2, the reaction between dimedone, ethyl acetoacetate, ammonium acetate, and aromatic aldehydes in the presence of a chiral BINOL-phosphoric acid catalyst 7 gave compounds 8 in good to excellent yields and in enantiomeric excesses above 94%, although the absolute configuration of the final products was not determined [10]. 

DFT has been employed to probe the mechanisms of chiral BINOL-phosphoric-acid-catalysed allylboration and propargylation reactions, with a particular focus on whether the catalyst interacts with the pseudo-axial or pseudo-equatorial oxygen of the boronate. °... 

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]. 

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. 

Several chiral catalysts for conjugate addition have been explored, including both protic and Lewis acids. 3,3 -hri-(4-Nitrophenyl)-BINOL-phosphoric acid gives 40-98% yields and 40-55% ee with p-aryl enones [243]. 

The chiral catalysts that have been used in nitroaUcene conjugate additions include bw-oxazolines with Cu(OTF)2 [281] or Zn(OTf)2 [282], tridentate bw-oxazolines with Zn(OTf)2 [283], mixed thiazoline-oxazolines with Zn(OTf)2 [284], imidazoUne-aminophenols with CuOTf [285], bis-trifluoromethylsulfonamides [286], binaphthyl sulfonamides [287], binaphthyl imines [288], thioureas [289], and quinoUnyl thioureas [290]. A BINOL-phosphoric acid with 3A molecular sieves gave ee values consistently at 90% and above with both p-alkyl and p-aryl nitroalkenes [291]. 

Excellent enantioselectivity has also been obtained using 3,3 -6 s-(l-naphthyl) BINOL-phosphoric acids [311]. A -Tosyl imines of aryl aldehydes were also examined using a binaphthyl Pd(II) carbene complex as the catalyst. Enantioselectivity in the 50-75% range was obtained [312]. Imines formed from ot-phenylethylamine and ethyl 3,3,3-trifluoropyruvate give adducts with 85-97% de in the presence of TEA [313]. The chiral auxiliary can be removed by hydrogenolysis. 

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]. 

Later on, the Rueping group reported an organocatalytic enantioselective reduction of pyridine 180 (Scheme 17.30) [74], according to the procedure described by Bohlmann and Rahtz [75]. The key step in the synthesis of decahydroquinolines from the pumiliotoxin family involved Hantzsch dUiydropyridine 172 as the hydride source and involved BINOL-phosphoric acid 181 as a chiral Br0nsted acid catalyst... 

An a/ -stereo- and diastereo-selective glycosylation method employs a glucosyl a-trichloroacetimidate and a chiral BINOL-derived phosphoric acid catalyst the system selects the i -enantiomer of a racemic mixture of secondary alcohols. ... 

Strained allylic cyclobutanols and cyclopropanols undergo ring expansion promoted by a chiral binol-derived phosphoric acid catalyst to give 0-fluoro spiroketone products (Scheme 80). ... 

An insoluble cationic iodinating reagent, combined with a chiral binol-derived lipophilic phosphoric acid catalyst, has been found to act as an efficient source of chiral iodine that performs the semipinacol transposition of strained allylic alcohols to -iodo spiroketones B (Scheme 85). (Se)... 

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). 

At almost the same time, Akiyama et al. developed a similar aza-Darzens reaction using aldimines derived from aryl glyoxals and ethyl diazoacetate promoted by chiral BINOL-derived phosphoric acid catalysts, such as 90 (Scheme 37.17) [159]. In this case, the reaction rendered exclusively the corresponding cis-aziridine carboxylates in both excellent yields (95-100%) and enantioselectivities (92-97% ee). However, the scope of the method seemed to be quite narrow since only aromatic glyoxals were employed. 

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. 

Axially chiral phosphoric acid 3 was chosen as a potential catalyst due to its unique characteristics (Fig. 2). (1) The phosphorus atom and its optically active ligand form a seven-membered ring which prevents free rotation around the P-0 bond and therefore fixes the conformation of Brpnsted acid 3. This structural feature cannot be found in analogous carboxylic or sulfonic acids. (2) Phosphate 3 with the appropriate acid ity should activate potential substrates via protonation and hence increase their electrophilicity. Subsequent attack of a nucleophile and related processes could result in the formation of enantioenriched products via steren-chemical communication between the cationic protonated substrate and the chiral phosphate anion. (3) Since the phosphoryl oxygen atom of Brpnsted acid 3 provides an additional Lewis basic site, chiral BINOL phosphate 3 might act as bifunctional catalyst. 

In 2008, the Ackennann group reported on the use of phosphoric acid 3r (10 mol%, R = SiPhj) as a Brpnsted acid catalyst in the unprecedented intramolecular hydroaminations of unfunctionaUzed alkenes alike 144 (Scheme 58) [82], BINOL-derived phosphoric acids with bulky substituents at the 3,3 -positions showed improved catalytic activity compared to less sterically hindered representatives. Remarkably, this is the first example of the activation of simple alkenes by a Brpnsted acid. However, the reaction is limited to geminally disubstituted precursors 144. Their cyclization might be favored due to a Thorpe-Ingold effect. An asymmetric version was attempted by means of chiral BINOL phosphate (R)-3( (20 mol%, R = 3,5-(CF3)2-CgH3), albeit with low enantioselectivity (17% ee). 

Until 2006, a severe limitation in the field of chiral Brpnsted acid catalysis was the restriction to reactive substrates. The acidity of BINOL-derived chiral phosphoric acids is appropriate to activate various imine compounds through protonation and a broad range of efficient and highly enantioselective, phosphoric acid-catalyzed transformations involving imines have been developed. However, the activation of simple carbonyl compounds by means of Brpnsted acid catalysis proved to be rather challenging since the acid ity of the known BINOL-derived phosphoric acids is mostly insufficient. Carbonyl compounds and other less reactive substrates often require a stronger Brpnsted acid catalyst. 

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. 

In this chapter, we focus on recent achievements in the enantioselective synthesis of chiral amines using 1,1 bi 2 naphthol (BINOL) derived monophosphoric acid (1) or related phosphoric acids as chiral Bronsted acid catalysts 2, 3], The contents are arranged according to the type of bond forming reaction, including carbon carbon, carbon hydrogen, and carbon heteroatom bond forming reactions, followed by specific reaction types. 

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). 

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