Key words
N-triflylphosphorimidoyl trichloride - Brønsted acid -
N-triflylphosphoramide -
N-triflylthiophosphoramide -
N,
N′-bis(triflyl)phosphoramidimidate
Over the last decade, chiral phosphoric acid catalysts have attracted great attention because of their remarkable reactivity and ease of handling.[1] Since Akiyama and Terada had reported successful application of BINOL-derived phosphoric acids or their salts as catalysts in Mannich reactions, numerous catalyst variations have been developed by modifying the 3,3′-substituents of the BINOL backbone.[2] Furthermore, the Yamamoto group demonstrated that the activity of phosphoric acid catalysts can be enhanced by replacing the OH group with an N-triflyl group.[3] Due to the higher acidity of the resulting N-triflylphosphoramides, several groups successfully reported asymmetric reactions which could not be accomplished using the original phosphoric acids.[4] However, despite their utility, the synthesis of these catalysts requires a two-step procedure which involves a solvent change and a relatively long reaction time under heating.[3]
[5] During our studies on the development of even stronger Brønsted acid catalysts, we recently reported a practical method to introduce N-triflyl groups to molecular structures using N-triflylphosphorimidoyl trichloride (1) as a reagent (Scheme [1]). We have prepared this substance in a solid-state reaction between phosphorous pentachloride (PCl5) and trifluoromethansulfonylamide under reduced pressure.[6] When compound 1 was reacted with different BINOLs (2) in the presence of triethylamine or diisopropylethylamine in THF or toluene, intermediate 3 was formed within ten minutes. Adding 0.5 equivalent of ammonia or hexamethyldisilazane afforded the corresponding N-triflylphosphoramidimidate 4 in situ. With further heating under reflux, novel imidodiphosphorimidates (IDPi) 5 were obtained successively. On the basis of this observation, we wondered if it was possible to establish a new approach to Yamamoto catalysts, simply by hydrolyzing intermediate 3. Herein we report the fruition of these efforts with a general approach to various N-triflyl-substituted chiral Brønsted acids.
Scheme 1 Preparation of N-triflylphosphorimidoyl trichloride 1 and its application to the synthesis of imidodiphosphorimidates 5
Indeed, most BINOLs 2a–f, upon reaction with reagent 1 in dichloromethane and DIPEA, gave the corresponding intermediate 3 within 10 minutes. With sterically hindered BINOL 2g, the reaction took 1 hour until completion. Further reaction with water required only 10 minutes with chlorides 3a–f and 1 hour with compound 3g to furnish the corresponding acids. Products 6a–g were obtained in >80% yield regardless of the electronic or steric properties of the BINOL starting material (Table [1]).
Table 1 Substrate Scope of the Yamamoto-Type Brønsted Acid Synthesisa
|
|
Entry
|
Product
|
Config.
|
R
|
Yield (%)
|
|
1
|
6a
|
S
|
Ph
|
98
|
|
2
|
6b
|
R
|
4-PhC6H4
|
97
|
|
3
|
6c
|
S
|
1-Naph
|
90
|
|
4
|
6d
|
R
|
2-Naph
|
96
|
|
5
|
6e
|
S
|
9-phenanthryl
|
89
|
|
6
|
6f
|
S
|
3,5-(CF3)2C6H3
|
97
|
|
7
|
6g
|
S
|
2,4,6-i-Pr3C6H2
b
|
82
|
a Reactions were performed with 2 (1.0 equiv), 1 (1.1 equiv), and DIPEA (5.0 equiv) in CH2Cl2 (0.25 mL) for 10 min, and then H2O (20 μL) was added to hydrolyze the intermediates 3.
b In this case, substitution and hydrolysis reactions each took 1 h.
Scheme 2 Synthesis of N-triflylthiophosphoramides and N,N′-bis(triflyl)phosphoramidimidates
Next, we applied our method to synthesize other strong Brønsted acids (Scheme [2]). In 2008, the Yamamoto group exchanged the oxo group of their catalysts with a thio group. The resulting more acidic N-triflylthiophosphoramides successfully enabled catalytic enantioselective protonation reactions.[7] Later, our group exchanged the oxo group with an N-triflyl imino group expecting an even further increase in acidity.[8] In order to also obtain these two stronger acid motifs, intermediate 3 was reacted with H2S or with triflamide, respectively. The target acids 7 and 8 were readily obtained within 20 minutes or 1 day, depending on the substrates.
In summary, we have established a simple and practical route to synthesize strong chiral Brønsted acids. The method is effective for the preparation of N-triflylphosphoramides with electron-deficient, electron-rich, and sterically demanding substrates.[9] Furthermore, both of N-triflylthiophosphoramides and N,N′-bis(triflyl)phosphoramidimidates were prepared in high yields within one day. Further use of reagent 1 in catalyst development is currently underway in our laboratory.
