Simple Chiral Amine Research Articles

Enantioselective Synthesis of Phosphine Boranes via Crystallization-Induced Dynamic Resolution of Lithiated Intermediate by Understanding the Underlying Epimerization Process.

Described herein is the successful crystallization-induced dynamic resolution (CIDR) of an α-lithiated phosphine borane utilizing the easily accessible and inexpensive ligand (R,R)-TMCDA. Starting from the essential P-prochiral building block dimethyl phenyl phosphine borane we were able to obtain phosphine boranes in yields up to 80 % and e.r. up to 98 : 2 by crystallization of the lithiated intermediate prior to the trapping reaction. NMR-based deuterium labeling experiments indicate that the epimerization in solution is based on the intermolecular proton transfer between nonlithiated phosphine borane and the corresponding lithiated intermediate, rendering the presence of the remaining starting compound in an optimized solvent mixture the main factor for successful enantioselective synthesis. Quantum chemical calculations using different model systems based on solid state structures confirm these experimental results. By gaining insights into the epimerization mechanism, essential principles for CIDR of lithiated phosphine boranes are elucidated that may be expanded to other important P-stereogenic compounds and simple chiral amines.

Enantioselektive Synthese von Phosphinoboranen via kristallisationsinduzierter dynamischer Racematspaltung des lithiierten Intermediates durch Verständnis des zugrunde liegenden Epimerisierungsprozesses

AbstractHier wird die erfolgreiche kristallisationsinduzierte dynamische Racematspaltung (CIDR) eines α‐lithiierten Phosphinoborans mithilfe des leicht zugänglichen und kostengünstigen chiralen Liganden (R,R)‐TMCDA beschrieben. Ausgehend von dem wichtigen P‐prochiralen Baustein Dimethylphenylphosphinoboran konnten Phosphinoborane in Ausbeuten von bis zu 80 % und Enantiomerenverhältnissen von bis zu 98 : 2 durch Kristallisation des lithiierten Zwischenprodukts erhalten werden. NMR‐basierte Deuterium‐Markierungsexperimente zeigen, dass die Epimerisierung in Lösung auf dem intermolekularen Protonentransfer zwischen dem nicht lithiierten Phosphinoboran und dem entsprechenden lithiierten Zwischenprodukt beruht, sodass die Anwesenheit überschüssigen Eduktes in einem optimierten Lösungsmittelgemisch der Hauptfaktor für eine erfolgreiche enantioselektive Synthese ist. Quantenchemische Berechnungen mit verschiedenen auf Festkörperstrukturen basierenden Modellsystemen bestätigen diese experimentellen Ergebnisse. Durch den Einblick in den Epimerisierungsmechanismus wurden wesentliche Prinzipien für die CIDR von lithiierten Phosphinoboranen aufgeklärt, die auf andere wichtige P‐stereogene Verbindungen und einfache chirale Amine erweitert werden könnten.

Counterion-Enhanced Pd/Enamine Catalysis: Direct Asymmetric α-Allylation of Aldehydes with Allylic Alcohols by Chiral Amines and Achiral or Racemic Phosphoric Acids.

We report a straightforward and efficient Pd/enamine catalytic procedure for the direct asymmetric α-allylation of branched aldehydes. The use of simple chiral amines and easily prepared achiral or racemic phosphoric acids, together with a suitable Pd-source resulted in a highly active and enantioselective catalyst system for the allylation of various α-branched aldehydes with different allylic alcohols. The reported procedure could provide an easy access to both product antipodes. Furthermore, two possible orthogonal derivatizations of the enantioenriched aldehydes were performed without any decrease in enantioselectivity.

Highly enantioselective cascade transformations by merging heterogeneous transition metal catalysis with asymmetric aminocatalysis.

The concept of combining heterogeneous transition metal and amine catalysis for enantioselective cascade reactions has not yet been realized. This is of great advantage since it would allow for the recycling of expensive and non-environmentally friendly transition metals. We disclose that the use of a heterogeneous Pd-catalyst in combination with a simple chiral amine co-catalyst allows for highly enantioselective cascade transformations. The preparative power of this process has been demonstrated in the context of asymmetric cascade Michael/carbocyclization transformations that delivers cyclopentenes bearing an all carbon quaternary stereocenters in high yields with up to 30:1 dr and 99% ee. Moreover, a variety of highly enantioselective cascade hetero-Michael/carbocyclizations were developed for the one-pot synthesis of valuable dihydrofurans and pyrrolidines (up to 98% ee) by using bench-stable heterogeneous Pd and chiral amines as co-catalysts.

Direct Regiospecific and Highly Enantioselective Intermolecular α‐Allylic Alkylation of Aldehydes by a Combination of Transition‐Metal and Chiral Amine Catalysts

The first direct intermolecular regiospecific and highly enantioselective α-allylic alkylation of linear aldehydes by a combination of achiral bench-stable Pd(0) complexes and simple chiral amines as co-catalysts is disclosed. The co-catalytic asymmetric chemoselective and regiospecific α-allylic alkylation reaction is linked in tandem with in situ reduction to give the corresponding 2-alkyl alcohols with high enantiomeric ratios (up to 98:2 e.r.; e.r.=enantiomeric ratio). It is also an expeditious entry to valuable 2-alkyl substituted hemiacetals, 2-alkyl-butane-1,4-diols, and amines. The concise co-catalytic asymmetric total syntheses of biologically active natural products (e.g., Arundic acid) are disclosed.

One‐Pot Three‐Component Catalytic Enantioselective Synthesis of Homoallylboronates

No longer a simple bor(ation): The title reaction between bis(pinacolato)diboron, enals, and 2-(triphenylphosphoranylidene)acetates employing bench-stable copper salts and a simple chiral amine co-catalyst is presented (see scheme). The reaction proceeds through a catalytic asymmetric conjugate borane addition/Wittig sequence wherein the β-boration step is 1,4-selective and gives the corresponding homoallylboronate products with high enantiomeric ratios.

Catalytic Enantioselective β‐Alkylation of α,β‐Unsaturated Aldehydes by Combination of Transition‐Metal‐ and Aminocatalysis: Total Synthesis of Bisabolane Sesquiterpenes

Branching out! The first co-catalytic enantioselective (up to 98:2 e.r.) β-alkylation of α,β-unsaturated aldehydes by combination of simple chiral amine and copper catalysts provides β-branched aldehydes in a one-pot protocol. The methodology was applied to the short total syntheses of bisabolane sesquiterpenes (S)-(+)-curcumene, (E)-(S)-(+)-3-dehydrocurcumene and (S)-(+)-tumerone.

ChemInform Abstract: Organocatalytic Enantioselective Aziridination of α‐Substituted α,β‐Unsaturated Aldehydes: Asymmetric Synthesis of Terminal Aziridines.

The first example of a highly enantioselective organocatalytic aziridination of α-substituted α,β-unsaturated aldehydes is presented. The reaction is catalyzed by simple chiral amines and gives acc ...

Enantioselective Conjugate Silyl Additions to α,β‐Unsaturated Aldehydes Catalyzed by Combination of Transition Metal and Chiral Amine Catalysts

AbstractWe report that transition metal‐catalyzed nucleophilic activation can be combined with chiral amine‐catalyzed iminium activation as exemplified by the unprecedented enantioselective conjugate addition of a dimethylsilanyl group to α,β‐unsaturated aldehydes. These reactions proceed with excellent 1,4‐selectivity to afford the corresponding β‐silyl aldehyde products 3 in high yields and up to 97:3 er using inexpensive bench stable copper salts and simple chiral amine catalysts. The reaction can also generate a quaternary stereocenter with good enantioselectivity. Density functional calculations are performed to elucidate the reaction mechanism and the origin of enantioselectivity.

Organocatalytic Enantioselective Aziridination of α‐Substituted α,β‐Unsaturated Aldehydes: Asymmetric Synthesis of Terminal Aziridines

AbstractThe first example of a highly enantioselective organocatalytic aziridination of α‐substituted α,β‐unsaturated aldehydes is presented. The reaction is catalyzed by simple chiral amines and gives access to highly functional terminal azirdines containing an α‐tertiary amine stereocenter in high yields and enantiomeric ratios (95.5:4.5–98:2).

Enantioselective Organocatalytic Conjugate Addition of Fluorocarbon Nucleophiles to α,β‐Unsaturated Aldehydes

A highly chemo- and enantioselective organocatalytic addition of fluorocarbon nucleophiles, such as 1-fluoro-bis(phenylsulfonyl)methane, toα,β-unsaturated aldehydes is presented (see scheme). The reactions are catalyzed by simple chiral amines and give access to optically active fluorine derivatives in good yields and up to 95 % ee. Notably, the methodology can be applied to the formation of a chiral quaternary carbon center bearing a fluorine atom with high enantioselectivity.

Chiral Amine–Polyoxometalate Hybrids as Recoverable Asymmetric Enamine Catalysts under Neat and Aqueous Conditions

AbstractSolid acid–chiral amine hybrids have been synthesized and explored as recyclable and reusable enamine‐type asymmetric catalysts. Simple chiral amine–polyoxometalate (CA–POM) hybrids were identified as the optimal catalysts to promote a range of enamine‐based transformations with high activity and excellent stereoselectivity under either neat or aqueous conditions. A catalyst loading as low as 0.33 mol‐% (1 mol‐% loading of chiral amine) was sufficient to achieve fast reactions and high stereoselectivities. Under both conditions, the CA–POM hybrid catalysts could be easily recycled and reused up to seven times with essentially unchanged stereoselectivity, although diminished activity was observed upon extensive reuse, especially under aqueous conditions.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Enantioselective Organocatalytic Hydrophosphination of α,β‐Unsaturated Aldehydes.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Enantioselective Organocatalytic Hydrophosphination of α,β‐Unsaturated Aldehydes

Keeping it simple: Optically active phosphine derivatives can be obtained in high yields and in up to 99% ee by using simple chiral amines to catalyze the hydrophosphination of α,β-unsaturated alde ...

Organocatalytic Enantioselective Aziridination of α,β‐Unsaturated Aldehydes

Simple chiral amines catalyze a highly chemo- and enantioselective aziridination of α,β-unsaturated aldehydes to provide 2-formylaziridines in good yields and with up to 99 % ee. The synthetic utility of this organocatalytic method was exemplified in a two-step asymmetric synthesis of β-amino acid esters with readily removable protecting groups (see scheme; R1=tert-butoxycarbonyl, benzyloxycarbonyl).

Phosphoric Acids as Amplifiers of Molecular Chirality in Liquid Crystalline Media

[structure: see text] A new system for the double amplification of the molecular chirality of simple chiral amines in achiral liquid crystalline media is described. It involves a conformationally flexible phosphoric acid based receptor that by binding to chiral amines induces chirality in the liquid crystalline matrix. Efficient cholesteric phase formation was shown by several chiral amines that were not able to induce measurable helicity in nematic liquid crystals by themselves.

Identification of a highly effective asymmetric phase-transfer catalyst derived from α-methylnaphthylamine

A library of quaternary ammonium salts has been generated via reaction of simple chiral amines with a series of conformationally dynamic biphenyl units. Screening of this library against the alkylation of a glycine imine has led to the identification of a highly effective asymmetric phase-transfer catalyst derived from α-methylnaphthylamine.

Amido‐Phosphane Ligands as P,O‐Chelates in Palladium‐Catalyzed Enantioselective Allylic Alkylations.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Amido-Phosphane Ligands as P,O-Chelates in Palladium-Catalyzed Enantioselective Allylic Alkylations

In the course of our study to develop didentate ligands that might provide wide bite angles in the metal chelation, we observed that a P,O-chelation mode could intervene with expected P,N-chelation in the palladium catalyzed allylic alkylations with aminophosphane ligands 1. 1 The P,Ochelation mode was supported by the X-ray crystal structure of the P,O-chelated palladium complex 2 (PF6 - counterion). 2 Also, a moderate enantioselectivity was obtained with the ligand 3, which suggested that other aminophosphane ligands, depicted as a general structure 4, might be developed as efficient ligands for the catalytic reactions. While a number of hetero-chelates such as P,N-, P,O- and P,S -chelates 3,4 have been developed for the catalytic reactions, neutral P,O-chelates based on carboxamide functionality have been rarely studied for that purposes: Intervention of the P,O-chelation mode in the catalytic reactions from amido-phosphane moiety have been observed earlier; 5,6 however, use of P,O-chelates based on carboxamide oxygens for the catalytic reactions appeared very recently. 7 Chiral P,O-chelates of amido-phosphane derivatives can be readily synthesized from various known chiral amines and carboxyphosphanes. We synthesized amidophosphanes from simple chiral amines and evaluated their ligand ability in the catalytic reaction. 8 Our study demonstrates that simple amido-phosphanes constitute a potentially useful ligand system for the palladium-catalyzed allylic alkylations.