Catalysts BINOL-phosphates

Recently, it has been shown by Hodgson and coworkers [195] that this domino reaction can indeed be performed in an enantioselective manner. Thus, treatment of 6/2-31 using the BINOL-phosphate Rh2-complex 6/2-34 at -15 °C gave (+)-6/2-33, probably via 6/2-32, in 66% yield and 90% ee (Scheme 6/2.6). Several other substrates and chiral catalysts have also been employed, though with lower selectivity. 

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. 

The Akiyama group tested various BINOL phosphates 3 as catalysts for the indirect Mannich reaction of aldimines 8 derived from 2-aminophenol with silyl ketene acetals 9 (Scheme 4). All of these Brpnsted acids furnished P-amino ester 10a in (nearly) quantitative yields. Both the reaction rates (4-46 h) and the enantioselectivities (27-87% ee) were strongly dependent on the nature of the substituents at the 3,3 -positions. 

List and coworkers reasoned that BINOL phosphates (specific Brpnsted acid catalysis) could be suitable catalysts for an asymmetric direct Pictet-Spengler reaction [26], Preliminary experiments revealed that unsubstituted tryptamines do not undergo the desired cyclization. Introduction of two geminal ester groups rendered the substrates more reactive which might be explained by electronic reasons and a Thorpe-Ingold effect. Tryptamines 39 reacted with aldehydes 40 in the presence of phosphoric acid (5)-3o (20 moI%, R = bearing 2,4,6-triisopropyI-... 

Two years later, Terada and coworkers described an asymmetric organocatalytic aza-ene-type reaction (Scheme 28) [50], BINOL phosphate (7 )-3m (0.1 mol%, R = 9-anthryl) bearing 9-anthryl substituents mediated the reaction of A-benzoylated aldimines 32 with enecarbamate 76 derived from acetophenone. Subsequent hydrolysis led to the formation of P-amino ketones 77 in good yields (53-97%) and excellent enantioselectivities (92-98% ee). A substrate/catalyst ratio of 1,000 1 has rarely been achieved in asymmetric Brpnsted acid catalysis before. 

Recently, several research gronps reported on the use of chiral BINOL phosphates as Brpnsted acid catalysts in MCRs involving imine activation. 

BINOL phosphate (5)-3o (10 mol%, R = 2,4,6- PTj-C Hj) turned out to be the catalyst of choice and gave iV-acetylated 3-indolyl amines 128 bearing a qnatemary stere-ogenic center in excellent yields (94-99%) with high enantioselectivities (73-97% ee). Enamides derived from aryl-methyl ketones as well as indoles with varions substitnents conld be employed. 

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). 

TRANSFER HYDROGENATION USING CHIRAL BINOL-PHOSPHATES AS CATALYSTS. 162... 

The absolute configuration of the amine 7 may be explained by a stereochemical model based on the X-ray crystal structure of the chiral BINOL-phosphate (Fig. 4). In the transition state the ketimine is activated by the Brpnsted acid in such a way, that the nucleophile has to approach from the less hindered si face as the re face is effectively shielded by the large aryl substituent of the catalyst (Fig. 4, left). Furthermore, a bifunctional activation seems to be plausible, where next to the ketimine protonation, the dihydropyridine is activated through a hydrogen bond from the Lewis basic oxygen of the phosphoryl group. 

Hence, initial explorations concentrated on varying the chiral BINOL-phosphate as well as reaction parameters including different protected imines, cyanide sources, catalyst loadings, temperatures, and concentrations. From these experiments the best results, with respect to yield and selectivity, were obtained with benzyl-protected aldimines and HCN at -40 °C using 10 mol% of catalyst 5b. 

BINOL-phosphates as efficient Brpnsted acid catalysts in the enantios-elective Strecker reaction shows that C-nucleophiles can be applied in the chiral ion-pair catalysis procedure. This, in turn, not only increases the diversity of possible transformations of this catalyst but also shows the great potential chiral Brpnsted acids in asymmetric catalysis. 

Hence, the initial reactions were conducted using BINOL-phosphate 5 in combination with various achiral Brpnsted acids, including pro-tonated pyridine derivatives, alcohols and acids. Best enantioselectiv-ities were observed with the addition of carbonic acids, phenol and hexafluoro isopropanol which provided the isoquinuclidines 28 with up to 88% ee. Further explorations concentrated on varying the reaction parameters including different protected imines, catalyst load-... 

Based on our earlier work, we assumed that the catalytic protonation of a divinylketone 31 by the BINOL-phosphate 5 would result in the formation of a cyclopentadienyl cation-phosphate anion adduct B. Subsequent conrotatory 4n-electrocyclization would lead to oxyallyl cation C which, via the elimination of a proton, will form enolate D. Successive protonation of this enolate should then result in the formation of cy-clopentenone 32 and the regenerated Brpnsted acid catalyst 5 (Fig. 12). 

At the outset of our experimental work we began by examining a suitable Brpnsted acid catalyst for the enantioselective electrocyclization of dienone 31. While the use of BINOL-phosphates resulted in the products 32 in good yields, better dia- and enantioselectivities were obtained with the corresponding iV-triflyl phosphoramides 33, which even at 0 °C gave complete conversion after 10 min. With the optimized conditions in hand, we applied various dienones to the Brpnsted acid catalyzed... 

An optimised chiral binol phosphate catalyst (87) for the hydrocyanation of imines provides a convenient strategy for the enantioselective synthesis of a-amino acids and diamines (Scheme 22). The same catalyst (87) has been used for cascade... 

Antilla et al. also investigated chiral calcium BINOL phosphate catalysts [94] for reviews of asymmetric phospination reactitMis, see [95, 96]. This type of calcium catalyst was apphed to asymmetric phosphinatimi reactions (Table 24). Not only a chiral magnesium phosphate but also a chiral calcium phosphate was... 

The group ofTsogoeva discovered that BINOL-phosphate catalyst 93 can promote the enantioselective addition of TMSCN to aliphatic hydrazones 92 (Table 30.12) [50]. The so-formed a-hydrazino nitriles 95 can be readily transformed via acidic hydrolysis into biologically and synthetically important a-hydrazino acids. In general, N-p-N02-benzoyl-protected ahphatic hydrazones 92 could be converted in good enantioselectivities (71-93% ee). The yields showed inconsistency, but... 

The lipophihc BINOL phosphate anion (30) has been identified as a superior phase-transfer catalyst for the asymmetric electrophilic fluorination of unsaturated amides (28) with the dication (31) to produce isoxazolines (29). ... 

In 2007, Rueping et al. reported an enantioselective Strecker reaction catalyzed by chiral BINOL phosphate 114 and TADDOL 115 catalysts (Fig. 7.11) [128]. The corresponding amino nitriles were obtained in good isolated yields and enantiose-lectivities (up to 97% ee). 

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