A-Triflyl phosphoramides

Keywords Asymmetric catalysis BINOL Dicarboxylic acids A-Triflyl phosphoramides Phosphoric acids Strong chiral Brpnsted acids... 

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. 

Whereas the established phosphoric acids showed no catalytic activity, A-triflyl phosphoramide (S)-4o (5 mol%, R = proved to be a highly effec-... 

An intriguing feature is that the previously unknown bisindoles 154 display atropisomerism as a result of the rotation barrier about the bonds to the quaternary carbon center. With the use of A-triflyl phosphoramide (1 )-41 (5 mol%, R = 9-phenanthryl), bisindole 154a could be obtained in 62% ee. Based on their experimental results, the authors invoke a Brpnsted acid-catalyzed enantioselective, nucleophilic substitution following the 1,2-addition to rationalize the formation of the bisindoles 154 (Scheme 65). 

In 2008, Yamamoto et al. disclosed an asymmetric 1,3-dipolar cycloaddition of diarylnitrones 156 with ethyl vinyl ether (157) (Scheme 66). Under the influence of the bulky chiral A-triflyl phosphoramide (5)-4s (5 mol%, R = 2,6- Prj-4-Ad-C Hj), the enrfo-products 158 were formed as the major diastereomers in good yields and enantioselectivities (66 to >99%, 7 1-32 1 endolexo, 70-93% ee(endo)) [86]. High asymmetric induction was achieved only with electron-deficient aryl groups on the nitrones. 

In the same year, Enders and coworkers reported an asymmetric one-pot, two-step synthesis of substituted isoindolines 159 in the presence of chiral A-triflyl phosphoramide (R)-Ae (10 mol%, R = d-NO -C H ) (Scheme 67) [87]. The cascade was triggered by a Brpnsted acid-catalyzed aza-Friedel-Crafts reaction of indoles 29 and A-tosyliminoenoates 160 followed by a DBU-mediated aza-Michael cyclization of intermediates 161 to afford the isoindolines 159 in high yields (71-99%) and short reaction times (10 min to 4 h) along with good enantioselectivities (52-90% ee). Longer reaction times (16 h to 10 days) caused increasing formation of the bisindole byproduct 162 (Scheme 68) along with amplified optical purity of isoindolines 159. 

An asymmetric intermolecular carbonyl-ene reaction catalyzed by 1 mol% of chiral A-triflyl phosphoramide (/ )-4t (1 mol%, R = 4-MeO-CgH ) was developed by Rueping and coworkers (Scheme 69) [88], Various a-methyl styrene derivatives 163 underwent the desired reaction with ethyl a,a,a-trifluoropyruvate 164 to afford the corresponding a-hydroxy-a-trifluoromethyl esters 165 in good yields along with high enantioselectivities (55-96%, 92-97% ee). The presence of the trifluoromethyl group was crucial and the use of methyl pyruvate or glyoxylate instead of 164 resulted in lower reactivities or selectivities. 

Chiral phosphoric acids mediate the enantioselective formation of C-C, C-H, C-0, C-N, and C-P bonds. A variety of 1,2-additions and cycloadditions to imines have been reported. Furthermore, the concept of the electrophilic activation of imines by means of phosphates has been extended to other compounds, though only a few examples are known. The scope of phosphoric acid catalysis is broad, but limited to reactive substrates. In contrast, chiral A-triflyl phosphoramides are more acidic and were designed to activate less reactive substrates. Asymmetric formations of C-C, C-H, C-0, as well as C-N bonds have been established. a,P-Unsaturated carbonyl compounds undergo 1,4-additions or cycloadditions in the presence of A-triflyl phosphoramides. Moreover, isolated examples of other substrates can be electrophil-ically activated for a nucleophilic attack. Chiral dicarboxylic acids have also found utility as specific acid catalysts of selected asymmetric transformations. 

A-Triflyl phosphoramides derived from BINOL are highly acidic chiral Brpnsted acids, and they are powerful catalysts for enantioselective C-C and C-X bond-forming reactions. Their design, structural features, and applications since their development in 2006 have been reviewed. 

Oxysulfenylation and oxyselenenylation of olefins, catalysed by chiral Brpnsted acids, have been reported to produce enantiomerically enriched tetrahydrofurans at <63% ee with dibenzoyl-tartaric acid and its derivatives as catalyst. Enantioselective desymmetrization of thiiranium and seleniranium ions (<50% and <84% ee, respectively) in the presence of chiral binaphthol-derived A(-triflyl phosphoramide as a catalyst has also been demonstrated. ... 

Recently, Rueping et al. [36] disclosed the first enantioselective Nazarov cyclization reaction organocatalyzed by a chiral Brpnsted acid. The proposed reaction pathway involves a conrotatory 4n electrocyclization of the divinyl ketone 83 leading to the formation of an enol intermediate which is then snbjected to enantioselective protonation by the chiral Brpnsted acid 82b. This electrocyclization-protonation reaction was conducted with various divinyl ketones 83 under optimized conditions, i.e. in the presence of the chiral A -triflyl phosphoramide 82b (5 mol%) in chloroform at -10°C, affording the corresponding cyclopentenones 84 with 67-78% ee (for examples, see 83a-c 84a-c, Scheme 3.44). 

In this review, we present asymmetric reactions catalyzed by stronger Brpnsted acids. The scope and limitations of chiral phosphoric acids, iV-triflyl phosphoramides, and dicarboxylic acids are described considering articles published until the middle of 2008. Although the mechanisms of a few transformations have been investigated in some detail, they are not the focus of this review. 

This observation denotes a stereoablative kinetic resolution taking place during the acid-catalyzed step, which was confirmed in experiments with racemic intermediate 161a giving scalemic Friedel-Crafts product 161a at 55% conversion upon treatment with iV-triflyl phosphoramide (7 )-4d and indole (Scheme 68). 

Prior to Yamamoto s entry into this field, the scope of chiral phosphoric acid catalysis was strictly limited to electrophiUc activation of imine substrates. By designing a catalyst with higher acidity it was suspected that activation of less Lewis basic substrates might be possible. To this end, Yamamoto reported incorporation of the strongly electron accepting N-triflyl group [57] into a phosphoric acid derivative to yield the highly acidic N-triflyl phosphoramide 13 (Scheme 5.32)... 

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... 

As a stronger Br0nsted acid, chiral binaphthol-based phosphoric acid 8 and /V-triflyl phosphoramide 9 were recently introduced to the FCA reaction of enones. Reports by a few groups on the alkylations of indoles showed that simple enones were still challenging substrates, and modest ee values were recorded with a few examples over 90% ee (Scheme 9.8) [23]. However, excellent enantioselectivities were achieved in the intramolecular C3 and N1 alkylations of indole by You and co-workers (Scheme 9.9) [24]. Noteworthy, chiral oxazaborolidinone and... 

Brpnsted acids such as thioureas represent hydrogen bonding catalysts (vide infra), while phosphoric acids, N-triflyl phosphoramides, and dicarboxylic acids are examples of stronger specific Brpnsted acids. In this section, examples of processes mediated by stronger Br0nsted acids are presented, focusing on phosphoric acids, A-trifiyl phosphoramides, and dicarboxylic acids (Figure 7). 

Stronger Brpnsted acid catalysts such as N-triflyl phospho-ramides. N-Triflyl phosphoramides were first apphed to the asymmetric Diels-Alder (DA) reaction of unsaturated ketones with silyloxydienes. While the established phosphoric acids demonstrated no catalytic activity, 5 mol% of N-triflyl phosphoramide 46 proved highly effective for the DA reaction of ethyl vinyl ketone with a range of sily-loxydienes, allowing access to highly enantioenriched endo products in good yields (35 to >99%, 82-92% ee) via a presumed boat transition state such as 47 (Scheme 7). 

In 2013, another intramolecular hydrosilojqrlation was combined with a Mukaiyama aldol condensation by Gong et al. in an enantioselective relay catalytic cascade. This domino reaction occurred between atylacetylene silanols and glyoxylates and was induced by a combination of an achiral gold catalyst and a chiral N-triflyl phosphoramide. As shown in Scheme 7.37,... 

Since the seminal reports from the Akiyama group [62] and the Terada group [63] in 2004, chiral phosphoric acid catalysis has become a very exciting field in the past few years [64-66]. Our group has made some efforts to increase the acidity of this type of catalysts through modifying chiral phosphoric acid structure to corresponding chiral W-triflyl phosphoramide [67, 68] or W-triflyl thio- and... 

A catal34ic asymmetric Nazarov cyclisation of fully-substituted die-nones (297) that provided cyclopentenone derivatives (298) with vicinal quaternary stereocenters in high optical purity and as single diastereo-isomers, has been carried out in the presence ofiV-triflyl phosphoramide (299) (Scheme 80). ... 

Although phosphoric acid has been employed for the activation of carbon-nitrogen double bond, Yamamoto et at. designed a stronger chiral Bronsted acid in order to expand the scope of the chiral Bronsted acid catalyzed reactions. A N-triflyl phosphoramide (50), bearing BINOL backbone, catalyzed the Diels-Alder reaction of a,p-unsaturated ketone with electron-rich diene ((2, )-siloxydiene is major) to give cyclohexene derivatives in high ees (Scheme 2.106) [184]. 

Quite recently. Rueping et al reported Nazarov cyclization reaction catalyzed by a phosphoramide (Scheme 2.107) [185]. Although phosphoric acid (41k) is effective for the Nazarov reaction, use of an N-triflyl phosphoramide (50b) improved the enantioselectivity. This is the first example of the enantioselective organocatalytic electrocyclization reaction. 

The Nazarov reaction belongs to a type of 4n electrocyclization and can usually be promoted by metal-based catalysts. In 2007, the first enantioselective organo-catalytic Nazarov reaction was reported by Rueping and coworkers [35aj. A chiral N-triflyl-phosphoramide 101 was a better selection for the cyclization of dienone substrates 102, and cyclopentenone products 103 were generated as a diastereo-meric mixture but with excellent enantioselectivity at low catalyst loadings (2 mol%) (Scheme 36.27). 

Recently, Maruoka et al. developed a chiral A7-triflyl phosphoramide-catalyzed alkylative cyclization of N-a-diazoacyloxazolidinones 183 and A7-Boc imines 182 to synthesize chiral aziridine 184 with high yield and excellent stereoselectivity " (Scheme 40.37). 

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