On the synthesis of a novel chiral phosphorodiamidic acid containing the α-phenylethyl moiety: Insights in its conformation and reactivity

A few years ago, the synthesis of chiral phosphoric acids supported on chiral BINOL frameworks was accomplished by T. Akiyama and M. Terada. Subsequent relevant applications demonstrated the importance of chiral phosphoric acids as privileged chiral inducers in asymmetric organocatalysis. In the present report we discuss the development of novel chiral phosphorodiamidic acids derived from C2-symmetric trans-1,2-diaminocyclohexane aliphatic frameworks. The preparation of the new chiral Brønsted acids, based on the intermediacy of a 1,3,2-diheterophospholan-2-oxide moiety, turned out to be challenging since several plausible synthetic methodologies proved to be ineffective. Furthermore, the five membered heterocyclic moiety turned out to be easily hydrolyzed when exposed to nucleophilic alcohols or water. Complementary to the successful multistep synthesis reported here, it was possible to obtain crystals of the key precursor of the desired phosphorodiamidic acid, which proved suitable for X-ray diffraction analysis and hence to establish important conformational characteristics of the novel heterocycle.

Chiral Brønsted acid-controlled intermolecular asymmetric [2 + 2] photocycloadditions

Control over the stereochemistry of excited-state photoreactions remains a significant challenge in organic synthesis. Recently, it has become recognized that the photophysical properties of simple organic substrates can be altered upon coordination to Lewis acid catalysts, and that these changes can be exploited in the design of highly enantioselective catalytic photoreactions. Chromophore activation strategies, wherein simple organic substrates are activated towards photoexcitation upon binding to a Lewis acid catalyst, rank among the most successful asymmetric photoreactions. Herein, we show that chiral Brønsted acids can also catalyze asymmetric excited-state photoreactions by chromophore activation. This principle is demonstrated in the context of a highly enantio- and diastereoselective [2+2] photocycloaddition catalyzed by a chiral phosphoramide organocatalyst. Notably, the cyclobutane products arising from this method feature a trans-cis stereochemistry that is complementary to other enantioselective catalytic [2+2] photocycloadditions reported to date.

Asymmetric synthesis of heterocyclic chloroamines and aziridines by enantioselective protonation of catalytically generated enamines

We report a method for the synthesis of chiral vicinal chlo-roamines via asymmetric protonation of catalytically gener-ated prochiral chloroenamines using chiral Brønsted acids. The process is highly enantioselective, with the origin of asymmetry and catalyst substituent effects elucidated by DFT calculations. We show the utility of the method as an approach to the synthesis of a broad range of heterocycle-substituted aziridines by treatment of the chloroamines with base in a one-pot process, as well as the utility of the process to allow access to vicinal diamines.

Hypercrosslinking chiral Brønsted acids into porous organic polymers for efficient heterogeneous asymmetric organosynthesis

Here, we certificated a construction strategy for directly immobilizing the axially chiral phosphoric acid into hypercrosslinked polymers by one-pot Friedel-Crafts alkylation reaction. They have high porosity, excellent stability and tailorable...

Chiral Brønsted Acids Catalyze Asymmetric Additions to Substrates that Are Already Protonated: Highly Enantioselective Disulfonimide-Catalyzed Hantzsch Ester Reductions of NH–Imine Hydrochloride Salts

While imines are frequently used substrates in asymmetric Brønsted acid catalysis, their corresponding salts are generally considered unsuitable reaction partners. Such processes are challenging because they require the successful competition of a catalytic amount of a chiral anion with a stoichiometric amount of an achiral one. We now show that enantiopure disulfonimides enable the asymmetric reduction of N–H imine hydrochloride salts using Hantzsch esters as hydrogen source. Our scalable reaction delivers crystalline primary amine salts in great efficiency and enantioselectivity and the discovery suggests potential of this approach in other Brønsted acid catalyzed transformations of achiral iminium salts. Kinetic studies and acidity data suggest a bifunctional catalytic activation mode.

Asymmetric acyl-Mannich reaction of isoquinolines with α-(diazomethyl)phosphonate and diazoacetate catalyzed by chiral Brønsted acids

α-Diazo-β-isoquinoline derivatives were obtained in excellent yields and enantioselectivities by asymmetric acyl-Mannich reaction of (diazomethyl)phosphonate or diazoacetate with isoquinolines.

A Scalable, One-Pot Synthesis of 1,2,3,4,5-Pentacarbomethoxycyclopentadiene

1,2,3,4,5-Pentacarbomethoxycyclopentadiene (PCCP) is a strong organic acid and a precursor to useful organocatalysts, including chiral Brønsted acids and silicon-based Lewis acids. The synthetic route to PCCP, first reported in 1942, is inconvenient for a number of reasons. The two-step synthesis requires the purification of intermediates from intractable side-products, high reaction temperatures, and extensive labor (3 days). We have developed an improved procedure that delivers PCCP efficiently in 24 hours in one pot at ambient temperature and without isolation.