Organocatalytic Enantioselective Synthesis Research Articles

Catalytic Enantioselective Synthesis of α‐(Benzylamino)cyclobutanones

AbstractAn organocatalytic enantioselective synthesis of α‐(benzylamino)cyclobutanones has been achieved by employing a tandem condensation/intramolecular rearrangement/proton transfer reaction and starting from racemic α‐hydroxycyclobutanone and a selection of benzylamines. This reaction sequence afforded the products in good to high yields with moderate to high enantioselectivities.

ChemInform Abstract: Organocatalytic Enantioselective Synthesis of 1‐Vinyl Tetrahydroisoquinolines Through Allenamide Activation with Chiral Broensted Acids.

Abstract1‐Vinyl tetrahydroisoquinoline ((R)‐II) is synthesized through a metal‐free strategy for a stereoselective Friedel—Crafts‐type cyclization reaction using an axial‐chiral phosphoric acid as catalyst.

Organocatalytic enantioselective synthesis of 1-vinyl tetrahydroisoquinolines through allenamide activation with chiral Brønsted acids

In this paper we present a new approach for the realization of tetrahydroisoquinoline scaffolds via stereoselective proto-activation of suitable allenamide precursors.

ChemInform Abstract: Asymmetric Synthesis of Tetrahydroquinolines via Saegusa‐Type Oxidative Enamine Catalysis/1,5‐Hydride Transfer/Cyclization Sequences.

Enantioselective organocatalytic synthesis of tetrahydroquinolines has been achieved via Saegusa-type oxidative enamine catalysis/1,5-hydride transfer/cyclization sequences. The feature of this research is a one-pot transformation of 3-aryl aldehydes into tetrahydroquinolines by using environmentally benign catalytic Saegusa oxidation and highly efficient internal redox reactions. The synthetically useful ring-fused tetrahydroquinoline derivatives were obtained in moderate yields and high levels of enantioselectivity.

ChemInform Abstract: Enantioselective Organocatalyzed Formal [4 + 2] Cycloaddition of Ketimines with Allenoates: Easy Access to a Tetrahydropyridine Framework with a Chiral Tetrasubstituted Stereogenic Carbon Center.

Enantioselective organocatalytic synthesis of tetrahydropyridines bearing a chiral tetrasubstituted carbon stereogenic center has been achieved. The spiro-type monoaryl phosphine catalyst, (R)-SITCP, was found to promote the formal [4+2] cycloaddition of saccharin-derived ketimines and α-methyl allenoate to afford the corresponding six-membered N-heterocycles in high yields and excellent regioselectivities with up to 93% ee.

Enantioselective one-pot synthesis of ring-fused tetrahydroquinolines via aerobic oxidation and 1,5-hydride transfer/cyclization sequences.

Enantioselective organocatalytic synthesis of tetrahydroquinolines has been achieved via an aerobic oxidation and a 1,5-hydride transfer/cyclization sequence. The feature of this research is a one-pot transformation of 3-arylprop-2-en-1-ol derivatives into tetrahydroquinolines using a Ru(VII)-catalyzed aerobic oxidation and highly efficient internal redox reactions. The synthetically useful ring-fused tetrahydroquinoline derivatives are obtained in moderate yields and high levels of enantioselectivity.

ChemInform Abstract: Catalytic Asymmetric One‐Pot Synthesis of α‐Methylene‐γ‐lactams.

Abstract An organocatalytic enantioselective synthesis of α-methylene-γ-lactams has been developed. The reaction between protected 2-aminomalonates and Morita–Baylis–Hillman carbonates is catalyzed by chiral Lewis bases to afford the corresponding lactams in excellent yields and moderate to good enantioselectivities, after work-up.

ChemInform Abstract: Enantioselective Organocatalytic Synthesis of α‐Cyclopropylphosphonates Through a Domino Michael Addition/Intramolecular Alkylation Reaction.

An organocatalytic domino reaction consisting of Michael addition/intramolecular alkylation between α,β-unsaturated aldehydes and bromophosphonoacetates was developed. Highly functionalised cyclopropylphosphonates containing three chiral centres, one of them quaternary, were obtained with good diastereoselectivities of up to 83:17 and very high enantioselectivities of up to 99 %.

ChemInform Abstract: Enantioselective Organocatalytic Synthesis of Sulfur‐Containing Spirocyclic Compounds.

AbstractTwo different enantioselective organocatalytic cascade reactions to form new sulfur‐containing spirocyclic scaffolds are described.

ChemInform Abstract: Organocatalytic Enantioselective Synthesis of 2,3‐Allenoates by Intermolecular Addition of Nitroalkanes to Activated Enynes.

AbstractThis is the first efficient intermolecular addition of nitroalkanes to activated enynes affording the title compounds under mild conditions.

From racemic to enantioselective total synthesis of trigonoliimines via development of an organocatalytic enantioselective Michael addition of α-aryl-α-isocyanoacetate to vinyl phenyl selenone.

Trigonoliimines are hexacyclic bisindole alkaloids isolated recently by Hao and co-workers. A synthesis of (±)-trigonoliimine B was accomplished in seven steps from simple starting materials featuring the Bischler-Napieralski reaction for closing the seven-membered ring with concomitant formation of an exoimine. Sulfolane was found to be the solvent of choice for this unprecedented transformation. An organocatalytic enantioselective synthesis of α,α'-disubstituted α-amino acids was subsequently developed using methyl α-aryl-α-isocyanoacetates as glycine templates and vinyl phenyl selenone as a Michael acceptor. Using one of this Michael adducts as a starting material, total synthesis of both (+)- and (-)-trigonoliimine A was subsequently realized.

ChemInform Abstract: Enantioselective Sulfonation of Enones with Sulfonyl Imines by Cooperative N‐Heterocyclic‐Carbene/Thiourea/Tertiary‐Amine Multicatalysis.

AbstractThis is the first organocatalytic enantioselective synthesis of β‐sulfonyl ketones.

Organocatalytic Enantioselective Multicomponent Synthesis of Pyrrolopiperazines

AbstractThe first organocatalytic multicomponent synthesis of enantioenriched pyrrolopiperazines is reported. These biologically relevant fused tricyclic products were obtained under catalytic iminium activation through a reaction sequence involving an enantioselective Michael addition followed by an iminium ion trapping via Pictet–Spengler cyclization (MAPS sequence). Substantial possibilities for variation on the three reaction partners [β‐keto ester, enal and N‐(2‐aminoethyl)pyrrole] along with excellent enantioselectivities are the highlights of the present transformation.magnified image

Organocatalytic cascade reactions: diversity-oriented synthesis for the construction of hydroisoquinoline scaffolds.

The organocatalytic enantioselective synthesis of highly functionalized hydroisoquinolines by trienamine-mediated [4+2]-cycloaddition/nucleophilic ring-closing reaction cascade sequence of cyanoacrylamides with 2,4-dienals is presented. The corresponding cycloadducts are formed in high yields and excellent stereoselectivities. Moreover, a series of transformations demonstrate the synthetic application of the obtained hydroisoquinolines.

Enantioselective Organocatalytic Synthesis of α‐Cyclopropylphosphonates through a Domino Michael Addition/Intramolecular Alkylation Reaction

AbstractAn organocatalytic domino reaction consisting of Michael addition/intramolecular alkylation between α,β‐unsaturated aldehydes and bromophosphonoacetates was developed. Highly functionalised cyclopropylphosphonates containing three chiral centres, one of them quaternary, were obtained with good diastereoselectivities of up to 83:17 and very high enantioselectivities of up to 99 %.

Organocatalytic Enantioselective Synthesis of 2,3-Allenoates by Intermolecular Addition of Nitroalkanes to Activated Enynes

The first efficient intermolecular addition of nitroalkanes to activated enynes for asymmetric synthesis of 2,3-allenoates is described. It is a new addition to the limited available strategies for catalytic asymmetric synthesis of allenoates. Enabled by a new bifunctional catalyst, a range of trisubstituted allenoates can be obtained in excellent chemical and optical purity. These allenoate products with a pendant 2-nitroethyl α-substituent are useful chiral building blocks.

Catalytic asymmetric one-pot synthesis of α-methylene-γ-lactams

An organocatalytic enantioselective synthesis of α-methylene-γ-lactams has been developed. The reaction between protected 2-aminomalonates and Morita–Baylis–Hillman carbonates is catalyzed by chiral Lewis bases to afford the corresponding lactams in excellent yields and moderate to good enantioselectivities, after work-up.

Enantioselective Organocatalytic Synthesis of Sulfur‐Containing Spirocyclic Compounds

AbstractTwo different enantioselective organocatalytic cascade reactions to form new sulfur‐containing spirocyclic scaffolds are described. In the first approach, benzothiophen‐2‐one and enals react in the presence of a secondary amine catalyst through a Michael/Michael/Aldol sequence to afford the final spiro‐cyclohexene carbaldehydes in good yields (up to 68 %) and with excellent selectivities [20:1 diastereomeric ratio (dr), up to 99 % ee]. In the second approach, the double Michael addition of benzothiophen‐2‐one to aromatic dienones with primary amine catalysis produces the corresponding spiro‐cyclohexanones in good yields (up to 76 %) and with moderate‐to‐high selectivities (up to 12:1 dr, up to 90 % ee). Moreover, the use of N‐phenylrhodanine as the bis‐nucleophile for these reactions also allowed the formation of the corresponding spirocyclic adducts.

ChemInform Abstract: Organocatalytic Enantioselective Synthesis of 2,3‐Dihydropyridazines

Abstractby reaction of hydrazone (I) with unsaturated aldehydes (II)

Organocatalytic enantioselective synthesis of 1,3,5-polyols by means of iterative asymmetric epoxidation: their application to the total synthesis of polyrhacitide A

We have developed a pragmatic route to the stereogenic skipped 1,3,5-polyols. The strategic transformation includes an organocatalytic enantioselective asymmetric epoxidation, which is either syn- or anti-selective as genesis of chirality and successive SN2 opening reaction by an appropriate functionalized nucleophile, followed by hydroboration/oxidation to generate stereoisomers in good yield. The critical intermediate generated en route to this process is employed in the total synthesis of polyrhacitide A.