Chiral Frustrated Lewis Pairs Research Articles

Asymmetric Hydrogenation of Acrylates by COF with Chiral Frustrated Lewis Pairs

Asymmetric Hydrogenation of Acrylates by COF with Chiral Frustrated Lewis Pairs

Stereocontrol via Propeller Chirality in FLP-Catalyzed Asymmetric Hydrogenation.

Utilization of chiral frustrated Lewis pairs as catalysts in enantioselective hydrogenation of unsaturated molecules represents a promising approach in asymmetric synthesis. In our effort to improve our current understanding of the factors governing the stereoselectivity in these catalytic processes, herein we examined the mechanism of direct hydrogenation of aromatic enamines catalyzed by a binaphthyl-based chiral amino-borane. Our computational analysis reveals that only one particular conformer of the key borohydride reaction intermediate can be regarded as a reactive form of this species. This borohydride conformer has a well-defined chiral propeller shape, which induces facial selectivity in the hydride transfer to pro-chiral iminium intermediates. The propeller chirality of the reactive borohydride conformer is generated by the axially chiral binaphthyl scaffold of the amino-borane catalyst through stabilizing π-π stacking interactions. This new computational insight can be readily used to interpret the high degree of stereoinduction observed for these reactions. We expect that the concept of chirality relay could be further exploited in catalyst design endeavors.

Asymmetric Partial Hydrosilylation of 2,2‐Difluoro‐1,3‐diketones with Chiral Frustrated Lewis Pairs

Comprehensive SummaryThe asymmetric partial reduction of 1,3‐diketones stands as a straightforward pathway to access optically active β‐hydroxyketones. In this paper, an asymmetric Piers‐type hydrosilylation of 2,2‐difluoro‐1,3‐diketones was successfully realized by using a frustrated Lewis pair of chiral borane and tricyclohexylphosphine as a catalyst, delivering a variety of α,α‐difluoro‐β‐hydroxyketones in high yields with up to 99% ee. Significantly, no over‐reduced diol products were observed even with an excess amount of silanes. The product can be conveniently converted to α,α‐difluoro‐β‐hydroxyester or 1,3‐anti‐diol via an oxidation with m‐CPBA or a reduction with DIBAL‐H without obvious loss of ee.

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

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

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

AbstractThe 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.

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.

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

In this paper, we demonstrate a metal-free asymmetric hydrogenation of acyclic α,β-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 Catalysis with Chiral Frustrated Lewis Pairs

The chemistry of frustrated Lewis pairs (FLPs) provides the most important approach for the metal‐free hydrogenation and hydrosilylations. Great progress has been achieved in this area for the past decade. Some promising results have also been obtained. This perspective article mainly focuses on the recent advances for the synthesis of chiral Lewis acidic boranes in category of three protocols, 1) hydroboration of chiral internal alkenes with Piers’ borane HB(C6F5)2; 2) in situ hydroboration of chiral alkenes or alkynes without any purification; 3) and substitution reaction of (C6F5)nBCl3–n with chiral organometallic reagents, as well as their applications in the metal‐free asymmetric hydrogenations and hydrosilylations. image

Chiral Frustrated Lewis Pairs Catalyzed Highly Enantioselective Hydrosilylations of Ketones

Summary of main observation and conclusionA highly enantioselective Piers‐type hydrosilylation of simple ketones was successfully realized using a chiral frustrated Lewis pair of tri‐tert‐butylphosphine and chiral diene‐derived borane as catalyst. A wide range of optically active secondary alcohols were furnished in 80%—99% yields with 81%—97% ee's under mild reaction conditions.

Design considerations for chiral frustrated Lewis pairs: B/N FLPs derived from 3,5-bicyclic aryl piperidines.

Herein, 3,5-bicyclic aryl piperidines are derivatized to generate chiral B/N FLPs. Initially, the twofold symmetric amine C6H2F2(C5H8NiPr) 1 was converted in a series of synthetic steps to the styrene-derivative C6HF2(C5H8NiPr)(CH[double bond, length as m-dash]CH2) 4. Efforts to hydroborate the vinyl fragment proved challenging as a result of the strongly basic nitrogen, although the species C6HF2(C5H8N(H)iPr)(CH2CH2B(OH)(C6F5)2) 5 was crystallographically characterized. Modification of the system was achieved by conversion of the amine C6H2F2(C5H8NH) 6 to C6HF2(C5H8NPh)(CH[double bond, length as m-dash]CH2) 9. Hydroboration of 9 with 9-BBN or HB(C6F5)2 gave C6HF2(C5H8NPh)(CH2CH2BBN) 10 or C6HF2(C5H8NPh)(CH2CH2B(C6F5)2) 11, respectively. The latter species was derivatized by complexation of PPh3 to give C6HF2(C5H8NPh)(CH2CH2B(C6F5)2)(PPh3) 12. The Lewis acidities of 10 and 11 were assessed by the Gutman-Beckett test and by computations of the FIA and GEI. While 10 did not effect HD scrambling or hydrogenation of N-phenylbenzylimine, 11 was effective in HD scrambling. Despite this, no reduction of N-t-butylbenzylimine or N-phenylbenzylimine was achieved. These data demonstrate that 10 lacks the threshold combination of Lewis acidity and basicity to activate H2, while 11 lacks the steric demands about boron to preclude classical Lewis acid-base bond formation with imine substrates.

Recent Advances in Organocatalyzed Asymmetric Hydrosilylations

Catalytic asymmetric hydrosilylation based on the use of inexpensive and handleable hydridic silanes is a very useful reaction in organic chemistry which has become the subject of special interest because of the intrinsic peculiarity of economic efficiency and environmental friendliness. Recently, a lot of structurally diverse organocatalysts have been designed and applied to this chemistry. Enantiopure organocatalysts such as formamide derivatives, picolinamide derivatives, S-chiral sulfinamide derivatives and chiral frustrated Lewis pairs (FLPs) have been proved as privileged catalysts for the enantioselective hydrosilylations. This manuscript provides an overview on the most relevant advances in this field and presents an extensive summary of the catalysis performance of the above mentioned catalysts. Keywords: Asymmetric reduction, hydrosilylations, organocatalysts, hydridic silanes, asymmetric synthesis, Lewis Bases.

ChemInform Abstract: Chiral Frustrated Lewis Pairs Catalyzed Highly Enantioselective Hydrosilylations of 1,2‐Dicarbonyl Compounds.

AbstractA variety of optically active α‐hydroxy ketones and esters is prepared utilizing the combination of tricyclohexylphosphine and chiral alkenylborane generated in situ from diyne as frustrated Lewis pair catalyst.

Chiral Frustrated Lewis Pairs Catalyzed Highly Enantioselective Hydrosilylations of 1,2-Dicarbonyl Compounds.

A highly enantioselective hydrosilylation of 1,2-dicarbonyl compounds was successfully realized for the first time utilizing the combination of tricyclohexylphosphine and chiral alkenylborane derived in situ from diyne as a frustrated Lewis pair catalyst. A variety of optically active α-hydroxy ketones and esters were obtained in 52-98% yields with 86-99% ee's.

ChemInform Abstract: A Highly Enantioselective Hydrogenation of Silyl Enol Ethers Catalyzed by Chiral Frustrated Lewis Pairs.

AbstractHighly enantioselective metal‐free hydrogenation of silyl enol ethers is achieved by combining P(tBu)3 with a chiral borane generated in situ by hydroboration of an axial‐chiral diene with HB(C6F5)2 as a frustrated Lewis pair catalyst.

ChemInform Abstract: Enantioselective Metal‐Free Hydrogenation Catalyzed by Chiral Frustrated Lewis Pairs

AbstractReview: 12 refs.

Enantioselective Metal‐Free Hydrogenation Catalyzed by Chiral Frustrated Lewis Pairs

Bulky Lewis acids and Lewis bases do not undergo neutralization to form classical Lewis acid–base adducts because of steric hindrance. The Lewis acids and Lewis bases involved in this phenomenon are termed “frustrated Lewis pairs” (FLPs). The synergy between the unquenched acid and base endows the Lewis pair with the ability to activate small molecules, in particular hydrogen. A milestone discovery in this field was reported by Stephan and co-workers in 2006, in which a phosphine–borane compound was reported to reversibly activate hydrogen under mild conditions. Since then, FLP chemistry has developed into a cutting-edge concept. Most of the reported FLPs, generally based on the strong Lewis acid B(C6F5)3 accompanied by a bulky amine or phosphine, may serve as hydrogenation catalysts. Recently, metal-free hydrogenation using FLP catalysts has been regarded as a promising application of FLP chemistry. FLP catalytic systems are able to hydrogenate a wide range of unsaturated substrates, such as imines, enamines, enol ethers, and heterocycles. Enantioselective hydrogenation, which is still dominated by transition-metal catalysts, plays a pivotal role in organic synthesis. Considering the increasingly stringent limits on the amount of metal impurities found in drug compounds, the development of an effective metal-free catalyst for enantioselective hydrogenation to synthesize chiral molecules is a longterm challenge. FLP-type enantioselective hydrogenation is a rational extension of this hydrogenation chemistry owing to its significant potential for the transition-metal-free synthesis of chiral molecules. However, FLP-type catalytic enantioselective hydrogenation has remained relatively unexplored. This strategy is hampered by the design and synthesis of an effective chiral borane reagent because this class of air-sensitive compound cannot be purified by the usual chromatography techniques. Another issue confronting researchers is that the stereoselectivity of borane connected to the chiral scaffold through a single s bond is difficult to control because two perfluorophenyl groups are necessary to keep enough Lewis acidity for H2 activation. To realize FLP-type catalytic enantioselective hydrogenation, four kinds of chiral FLP catalysts can be considered (Scheme 1), mode I: chiral B moiety, achiral N(P) moiety; mode II : achiral B moiety, chiral N(P) moiety; mode III : intramolecular chiral FLP; mode IV: chiral B moiety, chiral N(P) moiety. Great progress has been made in the rational design of chiral FLP catalysts based on modes I–III in recent years, but mode IV remains to be explored (Figure 1). In mode I, the chiral B H species resulting from H2 activation is expected to undergo an asymmetric hydride transfer to proScheme 1. Enantioselective metal-free hydrogenation by means of an FLP strategy.

A highly enantioselective hydrogenation of silyl enol ethers catalyzed by chiral frustrated Lewis pairs.

Using a simple combination of tri-tert-butylphosphine and chiral borane generated in situ by the hydroboration of chiral diene with HB(C6F5)2 as a frustrated Lewis pair catalyst, a highly enantioselective metal-free hydrogenation of silyl enol ethers was successfully realized to furnish a variety of optically active secondary alcohols in 93-99% yields with 88->99% ee's.

Frustrated Lewis Pair Catalyzed Asymmetric Hydrogenation

Catalytic asymmetric hydrogenation of unsaturated substrates is one of the most important transformations in organic chemistry, which provides a significant approach to produce optically active compounds both in academia and chemical industry due to its atom-economy and high efficiency. Since the original work of Knowles and Sabacky in 1960s, transition-metal-catalyzed asymmetric hydrogenation has been well developed with great achievements. However, metal-free asymmetric hydrogenation utilizing molecular hydrogen is extremely challenging, and has long been an unsolved problem. Frustrated Lewis pairs(FLPs) with a combination of sterically encumbered Lewis acids and Lewis bases preclude the formation of classical Lewis acid-base adducts via dative bonds due to the steric effects, and they therefore possess novel and interesting properties and reactivities. Since frustrated Lewis pairs was first disclosed to enable heterolytic cleavage of H2reversibly by Stephan and co-workers in 2006, its applications on activating various of small molecules such as H2, CO2, NO and catalytic hydrogenation of unsaturated compounds were reported. Asymmetric hydrogenation under H2 by metal-free catalysts has been realized and has witnessed important progress. In this perspective, the achievements on frustrated Lewis pair catalyzed asymmetric hydrogenation are discussed from two aspects:(1) asymmetric hydrogenation induced by chiral substrates;(2) asymmetric hydrogenation catalyzed by chiral frustrated Lewis pairs.

Chiral Dienes as “Ligands” for Borane-Catalyzed Metal-Free Asymmetric Hydrogenation of Imines

This paper describes a highly enantioselective metal-free hydrogenation of imines using chiral dienes as "ligands" for the generation of catalysts with HB(C6F5)2 by hydroboration in situ to furnish a variety of chiral amines with up to 89% ee, which provides a practical strategy for the development of novel chiral frustrated Lewis pairs for asymmetric hydrogenation.

ChemInform Abstract: Enantioselective Hydrosilylation with Chiral Frustrated Lewis Pairs.

AbstractThe asymmetric hydrosilylation of a variety of aromatic imines is efficiently achieved using a novel chiral frustrated Lewis pair catalyst (I).