A Highly Enantioselective Brønsted Acid Catalyst for the Strecker Reaction

Rueping, Magnus; Sugiono, Erli; Azap, Cengiz

doi:10.1002/anie.200504344

Cited by 208 publications

(94 citation statements)

References 50 publications

(4 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Recently, hydrogen-bond donors such as ureas/thioureas, [10][11][12][13][14][15][16][17][18][19][20][21][22][23] BINOL/diols, [24][25][26][27][28][29][30][31][32] and phosphoric acids [33][34][35][36][37][38][39][40] have been also recognized as efficient organocatalysts. Novel urea and thiourea derivatives were developed as organocatalysts and their potential as a general acid has been successfully demonstrated by several groups.…”

Section: Introductionmentioning

confidence: 99%

Development of Chiral Thiourea Catalysts and Its Application to Asymmetric Catalytic Reactions

2010

View full text Add to dashboard Cite

We have developed several multifunctional thiourea catalysts bearing a tertiary amine or an 1,2-amino alcohol in expectation of their synchronous activation of a nucleophile and an electrophile through both acid-base and hydrogen-bonding interactions. From these studies, it was revealed that the weak acidity of thioureas compared with metallic Lewis acids could be overcome by this modification. The bifunctional aminothiourea could be used efficiently for a wide range of diastereoselective and enantioselective nucleophilic reactions such as Michael addition of 1,3-dicarbonyl compounds to nitroolefines, aza-Henry reaction of nitroalkanes to N-Boc imines, and hydrazination of cyclic b b-keto esters. We also discovered that multifunctional thiourea catalyst, bearing an 1,2-amino alcohol moiety, significantly accelerated the Petasis-type reaction of alkenylboronic acids to Nphenoxycarbonyl quinolinium salts, prepared from quinolines and phenyl chloroformate, to afford 1,2-addition products with high enantioselectivity (up to 97% ee). Furthermore, to expand the synthetic applicability of the thiourea-catalyzed asymmetric reactions, tandem organocatalyzed reactions were explored to establish the concise one-pot synthesis of chiral densely functionalized three-, five-, and six-membered compounds.

show abstract

Section: Introductionmentioning

confidence: 99%

Development of Chiral Thiourea Catalysts and Its Application to Asymmetric Catalytic Reactions

2010

View full text Add to dashboard Cite

show abstract

“…Subsequent addition of HCN results in formation of the corresponding amino nitrile and the regenerated Brønsted acid catalyst. [11] Based on our previous results and observations, we herein report the application of yet another metalfree catalyst, the chiral TADDOL, for the hydrocyanation of aldimines. Furthermore, we describe the BINOL phosphate-catalyzed asymmetric Strecker reaction of ketoimines, which is generally not only more difficult to achieve as compared to the hydrocyanation of aldimines, [4h-j,5d] but additionally leads to the formation of valuable quaternary amino acids.…”

mentioning

confidence: 96%

Metal‐Free, Enantioselective Strecker Reactions Catalyzed by Chiral BINOL and TADDOL Catalysts

2007

Self Cite

View full text Add to dashboard Cite

An efficient, metal-free Brønsted acidcatalyzed, enantioselective hydrocyanation of ketoimines has been developed. This BINOL phosphate-catalyzed Strecker reaction provides the corresponding amino nitriles, precursors of quaternary amino acids, in good isolated yields and enantioselectivities. Additionally, we demonstrate that chiral diols, such as TADDOL, are effective enantioselective catalysts for the hydrogen-bond activation of aldimines.Keywords: amino acids; BINOL phosphate; Brønsted acid; hydrocyanation; Strecker reaction; TADDOL The addition of hydrogen cyanide to imines, the Strecker reaction, constitutes one of the most direct and practical methods for the synthesis of a-amino acids and derivatives.[1] As a result, considerable effort has been devoted towards the development of asymmetric Strecker reactions. [2,3] In addition to various metal-catalyzed hydrocyanations, [4] promising metal-free enantioselective variants [5] have been described. Recently, we reported that chiral Brønsted acids [6,7] are efficient catalysts for highly enantioselective processes, including the hydrogenation of ketoimines, [8a,b] benzoxazines, benzthiazines, benzoxazinones [8c] and quinolines, [9] as well as direct MannichMichael reactions, [10] or the hydrocyanation of aldimines (Scheme 1). [11] In this reaction the aldimine is protonated by a chiral BINOL phosphate 1 which leads to the formation of a chiral iminium ion, a chiral ion pair. Subsequent addition of HCN results in formation of the corresponding amino nitrile and the regenerated Brønsted acid catalyst. [11] Based on our previous results and observations, we herein report the application of yet another metalfree catalyst, the chiral TADDOL, for the hydrocyanation of aldimines. Furthermore, we describe the BINOL phosphate-catalyzed asymmetric Strecker reaction of ketoimines, which is generally not only more difficult to achieve as compared to the hydrocyanation of aldimines, [4h-j,5d] but additionally leads to the formation of valuable quaternary amino acids.We initially started our investigation with the exploration of various BINOL phosphates 1a-f in the hydrocyanation of ketoimine 4 (Table 1). The best results with regard to reactivity and selectivity were obtained with catalytic amounts of 1a (5 mol %) providing amino nitrile 5 in 70 % ee (Table 1, entry 1). All other tested BINOL phosphate catalysts gave inferior results which is in agreement with our earlier developed Brønsted acid-catalyzed reactions where sterically more congested 3,3'-aryl substituents on the BINOL skeleton gave generally better results. All cyanation reactions were performed in toluene at À40 8C with 1.5 equivs. of in situ generated HCN. [12] Other cyanide sources tested, such as trimethylsilyl cyanide or acetone cyanohydrin did not lead to the desired products.Further examinations concentrated on the solvent employed, as it was previously shown to have an important impact on reactivity and selectivity in Brønst-ed acid-catalyzed transformations. In accordance with the BINOL...

show abstract

“…[4] [6] Wir begannen unsere Studie mit der Suche nach dem passenden Brønsted-Säure-Katalysator [7] sowie der Untersuchung und Optimierung der Reaktionsparameter wie Katalysatormenge, Hydridquelle, Temperatur und Substratkonzentration. Die besten Ergebnisse hinsichtlich Reaktivität, Ausbeute und Selektivität wurden mit Brønsted-Säure-Katalysatoren des Typs 1, [5,8,9] in 2-Stellung substituierten Chinolinderivaten 2 und dem Hantzsch-Dihydropyridin 4 als Hydridquelle [5,6,10] erzielt. Nachfolgende Untersuchungen richteten sich auf die spezielle Katalysatorstruktur (Tabelle 1).…”

unclassified

“…Dies ist analog zu der kürzlich beschriebenen Binolphosphat-katalysierten Strecker-Reaktion. [9] Die höchsten Selektivitäten wurden mit Katalysator 1 f erzielt, der unter optimierten Bedingungen das 2-Phenyltetrahydrochinolin mit 97 % ee ergab (Tabelle 1, Nr. 6).…”

unclassified

“…6). [5,9] Unter den optimierten Bedingungen wurde im nächsten Schritt der Substratbereich der Brønsted-Säure-katalysierten Kaskaden-Transferhydrierung anhand 2-substituierter Chinolinderivate getestet (Tabelle 3). Diverse Tetrahydrochinoline mit aromatischen, heteroaromatischen und aliphatischen Resten konnten in guten Ausbeuten und mit hohen Enantioselektivitäten isoliert werden.…”

unclassified

See 1 more Smart Citation

Eine hoch enantioselektive Brønsted‐Säure‐katalysierte Kaskadenreaktion: organokatalytische Transferhydrierung von Chinolinen und deren Anwendung in der Synthese von Alkaloiden

2006

Self Cite

View full text Add to dashboard Cite

A Highly Enantioselective Brønsted Acid Catalyst for the Strecker Reaction

Cited by 208 publications

References 50 publications

Development of Chiral Thiourea Catalysts and Its Application to Asymmetric Catalytic Reactions

Development of Chiral Thiourea Catalysts and Its Application to Asymmetric Catalytic Reactions

Metal‐Free, Enantioselective Strecker Reactions Catalyzed by Chiral BINOL and TADDOL Catalysts

Eine hoch enantioselektive Brønsted‐Säure‐katalysierte Kaskadenreaktion: organokatalytische Transferhydrierung von Chinolinen und deren Anwendung in der Synthese von Alkaloiden

Contact Info

Product

Resources

About