Asymmetric Transfer Hydrogenation of 2-Substituted Quinoxalines with Regenerable Dihydrophenanthridine.

The asymmetric hydrogenation of quinoxalines represents one of the most efficient approaches for the synthesis of optically active tetrahyroquinoxalines. In this paper, we demonstrate a metal-free asymmetric transfer hydrogenation of 2-substituted quinoxalines with regenerable dihydrophenanthridine under H2 using a combination of chiral phosphoric acid and achiral borane as catalysts. A wide range of optically active 2-substituted tetrahydroquinoxalines were produced in high yields with ≤98% ee.

Stereoselective Hydrosilylation of 1,2-Diketones Catalyzed by Chiral Frustrated Lewis Pairs.

The asymmetric reduction of 1,2-diketones for the synthesis of optically active 1,2-diols, especially 1,2-anti-diols, remains a formidable challenge. In this paper, we describe the first highly stereoselective hydrosilylation of unsymmetrical vicinal diketones with PhSiH3 by using a chiral frustrated Lewis pair (FLP) catalyst, giving a variety of 1,2-diaryl-1,2-anti-diols in high yields with excellent d.r. values and up to 97 % ee. The chiral FLP catalyst exhibits the ability to control regio-, diastereo- and enantioselectivites concurrently.

Synthesis of Tetrasubstituted Enamines through Borane-Catalyzed Hydrogenations.

This paper describes a B(C6F5)3-catalyzed hydrogenation of ß-substituted α,ß-unsaturated imines by using as low as 0.2 mol % catalyst. A variety of tetrasubstituted enamines were afforded in 95-99% yields. It provides an efficient and facile way without the need for column chromatography purification.

Asymmetric catalysis with FLPs.

Chiral catalysts play a crucial role in the realm of asymmetric catalysis. Since their breakthrough discovery in 2006, chiral frustrated Lewis pairs (FLPs) have risen as a novel catalyst category for a broad range of metal-free asymmetric reactions. This review provides an overview of the remarkable progress made in this field over the past 15 years. The design and synthesis of chiral FLPs and their applications in hydrogenation, hydrosilylation, transfer hydrogenation, and various other reactions are summarized and highlighted.

Asymmetric Hydrogenations of Acyclic α,ß-Unsaturated Ketones with Chiral Frustrated Lewis Pairs (FLPs).

In this paper, we demonstrate a metal-free asymmetric hydrogenation of acyclic α,ß-unsaturated ketones under the catalysis of a frustrated Lewis pair (FLP) comprising chiral oxazoline and achiral borane. A wide range of optically active α-substituted ketones were furnished in high yields with 26-85% ee's.

Asymmetric Hydrogenation of Hydrazones with Chiral Boranes.

An enantioselective metal-free hydrogenation of hydrazones has been realized successfully using chiral boranes as catalysts, producing a range of optically active hydrazines in 87-99% yields with 75-93% ee's. The bulky 2,2,6,6-tetramethylpiperidinyl moiety was found to be essential for achieving the high enantioselectivities.

Asymmetric Reduction of Quinolines: A Competition between Enantioselective Transfer Hydrogenation and Racemic Borane Catalysis.

A chiral phosphoric acid catalyzed asymmetric transfer hydrogenation of quinolines with regenerable dihydrophenanthridine derived by a borane-catalyzed hydrogenation of phenanthridine under H2 has been successfully realized. Despite the competition of a racemic hydrogenation pathway, a variety of tetrahydroquinolines were furnished in high yields with up to 91% ee.

B(C6F5)3-catalyzed metal-free hydrogenation of 2-oxazolones.

A metal-free hydrogenation of 2-oxazolones was successfully realized by using 10 mol% of B(C6F5)3 as the catalyst, giving a variety of 2-oxazolidinones in 70-98% yields. An enamine to imine process was believed to be involved in this reaction.

Asymmetric Hydrogenation by Relay Catalysis with FLPs and CPAs: Stereodivergent Synthesis of 3-Substituted Flavanones.

To access flavanones bearing two contiguous stereogenic centers, a metal-free asymmetric hydrogenation of racemic 3-alkylidene flavanones has been developed by relay catalysis with achiral FLPs and chiral phosphoric acids, which represents a successful detour for the challenging hydrogenation of 3-substituted flavones. A wide range of trans- and cis-flavanones were obtained in high yields and ≤97% ee.

Regenerable Dihydrophenanthridine via Borane-Catalyzed Hydrogenation for the Asymmetric Transfer Hydrogenation of Benzoxazinones.

The highly enantioselective transfer hydrogenation of benzoxazinones with chiral phosphoric acids under H2 was successfully achieved, where boranes promoted the hydrogenation of phenanthridine for the regeneration of dihydrophenanthridine as the hydrogen donor. A variety of dihydrobenzoxazinones were obtained in high yields with up to 99% ee. The current work provides a promising solution to unreactive substrates for frustrated Lewis pair-catalyzed asymmetric hydrogenation.

Asymmetric hydrogenation of TIPS-protected oximes with chiral boranes.

An enantioselective metal-free hydrogenation of TIPS-protected oximes has been successfully realized for the first time by using chiral borane catalysts derived from chiral dienes and Piers' borane. A variety of hydroxylamine derivatives were afforded in 84-99% yields with 33-68% ees.

Asymmetric Intramolecular Hydroalkoxylation of 2-Vinylbenzyl Alcohols with Chiral Boro-Phosphates.

Asymmetric intramolecular hydroalkoxylation of alkenes represents a very important approach to access optically active cyclic ethers. It was found that B(C6 F5 )3 could catalyze the cyclization of 2-vinylbenzyl alcohols with only 0.05 mol % catalyst loading, affording the desired product in high yields. To accomplish the asymmetric reaction, a novel type of chiral boro-phosphates was developed by treating chiral phosphoric acid with Piers' borane, in which the oxygen atom of P=O and the boron atom act as Lewis base and acid centers, respectively. A highly enantioselective hydroalkoxylation was successfully realized to give optically active 1,3-dihydroisobenzofuran derivatives in 78-99 % yields with 60-97 % ee's, in which an activation of O-H bond of alcohols by the boro-phosphate species is hypothesized.

Chiral FLP-catalyzed asymmetric hydrogenation of 3-fluorinated chromones.

The asymmetric hydrogenation of fluorinated olefins is an efficient pathway towards the synthesis of chiral fluorine-containing compounds. This paper described metal-free asymmetric hydrogenation of 3-fluorinated chromones with the use of readily available achiral borane and chiral oxazoline as an FLP catalyst for the first time. A variety of optically active 3-fluorochroman-4-ones were obtained in high yields with up to 88% ee.

Relay Catalysis by Achiral Borane and Chiral Phosphoric Acid in the Metal-Free Asymmetric Hydrogenation of Chromones.

A strategy of relay catalysis by achiral borane and chiral phosphoric acid was successfully developed for the asymmetric hydrogenation of chromones, giving the desired products in high yields with up to 95% ee. Achiral borane and chiral phosphoric acid are highly compatible in this reaction. The achiral borane acts as a Lewis acid for the first-step hydrogenation, and the chiral phosphoric acid acts as an effective chiral proton shuttle to control the enantioselectivity.

Asymmetric Halocyclizations of 2-Vinylbenzyl Alcohols with Chiral FLPs.

By the use of a chiral frustrated Lewis pair (FLP) consisting of a chiral-diene-derived borane and tBu3P as the catalyst, an asymmetric halocyclization of 2-vinylbenzyl alcohols with NBS or NIS was successfully realized. A variety of optically active 1,3-dihydroisobenofuran derivatives were obtained in high yields with up to 87% ee and could be conveniently converted to other useful chiral compounds.

Asymmetric Transfer Hydrogenation of N-Unprotected Indoles with Ammonia Borane.

A metal-free asymmetric transfer hydrogenation of unprotected indoles was successfully realized using a catalyst derived from HB(C6F5)2 and (S)-tert-butylsulfinamide with ammonia borane as a hydrogen source. A variety of indolines were achieved in 40-78% yields with up to 90% ee.

Asymmetric Hydrogenation of Ketones and Enones with Chiral Lewis Base Derived Frustrated Lewis Pairs.

The concept of frustrated Lewis pairs (FLPs) has been widely applied in various research areas, and metal-free hydrogenation undoubtedly belongs to the most significant and successful ones. In the past decade, great efforts have been devoted to the synthesis of chiral boron Lewis acids. In a sharp contrast, chiral Lewis base derived FLPs have rarely been disclosed for the asymmetric hydrogenation. In this work, a novel type of chiral FLP was developed by simple combination of chiral oxazoline Lewis bases with achiral boron Lewis acids, thus providing a promising new direction for the development of chiral FLPs in the future. These chiral FLPs proved to be highly effective for the asymmetric hydrogenation of ketones, enones, and chromones, giving the corresponding products in high yields with up to 95 % ee. Mechanistic studies suggest that the hydrogen transfer to simple ketones likely proceeds in a concerted manner.

B(C6F5)3-catalyzed divergent cyanosilylations of chromones dependent on temperature.

A B(C6F5)3-catalyzed divergent cyanosilylation of chromones has been successfully realized. A variety of 4-oxochromane-2-carbonitriles were furnished as kinetic products in high yields via 1,4-cyanosilylations. An unexpected C-O bond cyanosilylation was achieved when the temperature was raised to 80 °C, affording 4-oxo-4-(2-hydroxylphenyl)but-2-enenitriles as thermodynamic products in 72-94% yields, which was confirmed by DFT results.

B(C6F5)3-Catalyzed Highly Stereoselective Hydrogenation of Unfunctionalized Tetrasubstituted Olefins.

A metal-free hydrogenation of unfunctionalized tetrasubstituted olefins were successfully realized using a combination of B(C6F5)3 and Ph2NMe catalyst. The corresponding products were afforded in 58-98% yields with up to >99:1 cis/trans selectivity.

Carbonyl-Directed Addition of N-Alkylhydroxylamines to Unactivated Alkynes: Regio- and Stereoselective Synthesis of Ketonitrones.

A variety of ketonitrones were synthesized in moderate to excellent yields with high chemo-, regio-, and stereoselectivity by using carbonyl-directed addition of N-alkylhydroxylamines to unactivated alkynes under mild conditions. The product diverisity could be controlled by the use of different bases, and EtN( n-Pr)2 could promote the formation of ketonitrones while using EtONa as base led to indanone-derived nitrones. Control experiments indicated that the carbonyl group of the substrate acted as an H-bond acceptor except for an electron-withdrawing group, and conjugated enone skeleton accounted for the high selectivity.