Cinchona Alkaloids in Asymmetric Organocatalysis

Marcelli, Tommaso; Hiemstra, Henk

doi:10.1055/s-0029-1218699

Cited by 402 publications

(102 citation statements)

References 183 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…They can function as organocatalysts [1][2][3][4] and as an active surface component in heterogeneous reactions on supported metal catalysts [5][6][7][8][9]. Since cinchona organocatalysts can be tuned, through substitution, to stereodirect and accelerate a wide range of reactions they are classed as privileged chiral catalysts [10].…”

Section: Introductionmentioning

confidence: 99%

“…Since cinchona organocatalysts can be tuned, through substitution, to stereodirect and accelerate a wide range of reactions they are classed as privileged chiral catalysts [10]. Their action typically results from the cooperation of nucleophile activation by the quinuclidine group and electrophile activation by the hydroxy group [2][3][4]. These two functions are located in proximity to the stereogenic centres at C 8 and C 9 on the comparatively rigid skeleton of the alkaloid.…”

Section: Introductionmentioning

confidence: 99%

“…These two functions are located in proximity to the stereogenic centres at C 8 and C 9 on the comparatively rigid skeleton of the alkaloid. Transient non-covalent interactions with the two groups serve to pre-organize and regioselectively activate substrates [2][3][4]. Complications in the use of cinchona organocatalysts can arise from concentration dependent self-aggregation [11] and from disruption by the solvent of non-covalent bonding in the desired transition-state structure [4].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Disrupting Aryl-CH···O Interactions on Pt(111) Through the Coadsorption of Trifluoroacetic Acid and 2,2,2-Trifluoroacetophenone (TFAP): Inhibition of Competing Processes in Heterogeneous Asymmetric Catalysis

et al. 2011

View full text Add to dashboard Cite

A study of the coadsorption of trifluoroacetic acid (TFA) and 2,2,2-trifluoroacetophenone (TFAP) on Pt(111) was carried out using scanning tunneling microscopy (STM) measurements. The investigation is based on literature reports that the conversion rate and the enantiomeric excess for the hydrogenation of TFAP on cinchona modified Pt/Al 2 O 3 are very sensitive to the presence of small amounts of TFA in the solvent. As previously reported, STM and density functional theory (DFT) studies show that TFAP forms aryl-CHÁÁÁO bonded dimers on Pt(111) at room temperature. In the present study, STM measurements show that TFA disrupts aryl-CHÁÁÁO bonding through insertion into TFAP dimers to form isolated trimolecular and bimolecular assemblies. Structural models are proposed for the TFAP-TFA aggregates. The implications of these structures for the rate and enantioselectivity of TFAP hydrogenation are discussed in terms of H-bonding activation of the carbonyl function. It is proposed that the acid additive operates on the enanantioselective hydrogenation of TFAP through the inhibition of the racemic reaction at sites remote from the chiral modifier. This action is assumed to occur in parallel with effects, already proposed in the literature, due to the formation of modifier-acid complexes and the protonation of the modifier.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Disrupting Aryl-CH···O Interactions on Pt(111) Through the Coadsorption of Trifluoroacetic Acid and 2,2,2-Trifluoroacetophenone (TFAP): Inhibition of Competing Processes in Heterogeneous Asymmetric Catalysis

et al. 2011

View full text Add to dashboard Cite

show abstract

“…These catalysts were synthesized from primary amino acids and cinchona alkaloids derived amines. Cinchona alkaloids and their derivatives have tremendous applications [47][48][49][50][51][52][53][54] in asymmetric catalysis. As hydrogen bonding donor [16], the amide group of organocatalysts 3a-3h is crucial to the stabilization of the transition state according to the Houk-List [55][56][57] model.…”

Section: Introductionmentioning

confidence: 99%

Novel Primary Amine Organocatalysts Derived from Cinchona Alkaloids for Asymmetric Direct Aldol Reactions in Brine

et al. 2010

View full text Add to dashboard Cite

A series of Cinchona alkaloids derived organocatalysts have been developed and evaluated in the direct asymmetric intermolecular aldol reaction of 4-nitrobenzaldehyde and cyclohexanone. The catalyzed reactions of various aldehydes and ketones gave the corresponding aldol products with moderate to high enantioselectivities (up to 92%) and diastereoselectivities (up to [99/1, anti/syn) in the presence of 3e in brine.

show abstract

“…[7] Herein we present the first asymmetric catalytic C*ÀP bond formation employing a phosphine electrophile. By reacting asubstituted cyanoacetates (1) [8] with diaryl phosphine chlorides (2) under organocatalytic conditions, [9] optically active a-phosphinated cyanoacetates (3), which contain a stereogenic quaternary carbon center, are obtained (Scheme 1).Furthermore, 3 is transformed into protected chiral aquaternary a-phosphino b-amino acids [10] (4) by using a onepot procedure. This class of compounds might also be regarded as precursors for novel P,N ligands.…”

mentioning

confidence: 99%

Asymmetric Organocatalytic Electrophilic Phosphination

2011

View full text Add to dashboard Cite

The asymmetric incorporation of phosphorus-containing groups into target molecules is an important goal in diverse areas of synthetic chemistry. Organophosphorus compounds are used in various fields such as the synthesis of natural products [1] and their analogues, [2] ligands in organometallic catalysis, [3] organocatalysis, [4] and in general synthetic chemistry.[5] Hence, the development of asymmetric organocatalytic approaches towards optically active organophosphorus molecules is highly important.[6] A synthetic limitation is that previously the asymmetric catalytic formation of stereogenic carbon centers bonded to phosphorus (C*ÀP) has only been performed using nucleophilic phosphorus compounds. [7] Herein we present the first asymmetric catalytic C*ÀP bond formation employing a phosphine electrophile. By reacting asubstituted cyanoacetates (1) [8] with diaryl phosphine chlorides (2) under organocatalytic conditions, [9] optically active a-phosphinated cyanoacetates (3), which contain a stereogenic quaternary carbon center, are obtained (Scheme 1).Furthermore, 3 is transformed into protected chiral aquaternary a-phosphino b-amino acids [10] (4) by using a onepot procedure. This class of compounds might also be regarded as precursors for novel P,N ligands.[3f]Initially, we focused on the formation of a-phosphinated cyanoacetates (3), in which an equivalent of HCl is produced during the course of the reaction. Previously, phase-transfer catalysis (PTC) has been shown to be a useful protocol for this type of reaction.[11] However, several attempts using PTC failed to produce any traceable amounts of 3.[12] We therefore turned our attention to the use of cinchona alkaloids. Pleasingly, using a stoichiometric amount of (DHQD) 2 PYR (5 ; Table 1) led to a 77 % conversion within 30 minutes under ambient reaction conditions. However, only traces of 3 were formed when 0.1 equivalent of 5 was employed, which was attributed to the protonation of the catalyst. We anticipated that this problem could be solved by employing a base capable of scavenging the acid. Indeed, the addition of an excess of proton sponge (1,8-bis(dimethylamino)naphthalene) [13] when using 10 mol % of 5 led to full conversion after 6 hours under ambient reaction conditions.Having established a catalytic system, extensive screening [12] resulted in the development of the reaction shown in Table 1, in which step a with subsequent oxidative protection of the phosphine (step b), nitrile reduction, and then N protection (step c), [14] provided highly enantioenriched 4 (up to 93 % ee) in good yields (> 85 % for each reaction step). The scope of this reaction was studied by carrying out a range of reactions, in which both the R and the ester substituents in 1, and the aryl substituents in 2 were varied (Table 1). All the yields reported in Table 1 are for the formation of 4 from 1, and are thus the result of four steps performed in a one-pot fashion.Initially, it was shown that employing either (DHQD) 2 PYR (5) or (DHQ) 2 PYR (dihydroquinine 2,5-diphenyl...

show abstract

Cinchona Alkaloids in Asymmetric Organocatalysis

Cited by 402 publications

References 183 publications

Disrupting Aryl-CH···O Interactions on Pt(111) Through the Coadsorption of Trifluoroacetic Acid and 2,2,2-Trifluoroacetophenone (TFAP): Inhibition of Competing Processes in Heterogeneous Asymmetric Catalysis

Disrupting Aryl-CH···O Interactions on Pt(111) Through the Coadsorption of Trifluoroacetic Acid and 2,2,2-Trifluoroacetophenone (TFAP): Inhibition of Competing Processes in Heterogeneous Asymmetric Catalysis

Novel Primary Amine Organocatalysts Derived from Cinchona Alkaloids for Asymmetric Direct Aldol Reactions in Brine

Asymmetric Organocatalytic Electrophilic Phosphination

Contact Info

Product

Resources

About