Vicinal Stereocenters Research Articles

Catalytic asymmetric formal total syntheses of (+)- and (-)-cycloclavine.

We report an expeditious catalytic asymmetric approach to clavine alkaloids via a key Heck cyclization. This reaction sets the formation of vicinal stereocenters with excellent diastereoselectivity. Utilizing the aforementioned strategy, the formal total synthesis of cycloclavine (1) has been achieved via another key late-stage ester-aminolysis of 6.

Ir/Zn Dual Catalysis: Enantioselective and Diastereodivergent α-Allylation of Unprotected α-Hydroxy Indanones.

A one-step enantioselective and diastereodivergent α-allylation of unprotected α-hydroxy indanones has been developed using an Ir/Zn dual catalyst system; no additional base is required. The cyclic tertiary α-hydroxyketones containing vicinal stereocenters can be synthesized with excellent enantioselectivity (up to >99% ee) and good diastereoselectivity (up to 12:1 dr). By a simple choice of the appropriate chiral metal catalyst combination, all four product stereoisomers could be obtained from the same starting materials and under identical conditions.

Iron-Catalyzed Asymmetric Haloazidation of α,β-Unsaturated Ketones: Construction of Organic Azides with Two Vicinal Stereocenters.

Organic azides play important roles in synthetic chemistry, chemical biology, drug discovery, and material science. Azido-functionalization of alkenes is one of the most efficient procedures for rapid introduction of azide group into organic compounds. But only a few examples have been documented in the catalytic asymmetric version of the azidation of alkenes. Herein, we report an unprecedented highly diastereo- and enantioselective bromoazidation of α,β-unsaturated ketones catalyzed by chiral N,N'-dioxide/Fe(OTf)2 complexes. An array of aryl, heteroaryl, and alkyl substituted α,β-unsaturated ketones were transformed to the corresponding α-bromo-β-azido ketones in high yields with excellent diastereo- and enantioselectivities. The catalytic system was also applicable for chloroazidation and iodoazidation of chalcone. Kinetic studies and some control experiments suggested that the reaction might proceed via a 1,4-addition/halogenation pathway.

Total Syntheses of Pyroclavine, Festuclavine, Lysergol, and Isolysergol via a Catalytic Asymmetric Nitro-Michael Reaction.

A catalytic enantioselective construction of vicinal stereocenters is reported. The reaction takes advantage of thiourea-catalyzed intramolecular nitronate addition onto α,β-unsaturated ester to afford exceptional levels of enantioselectivity (up to 97 % ee) with moderate diastereoselectivity (up to 4:1). Using this method, a cross-conjugated ester was synthesized in few steps, from which a 6-endo-trig cyclisation led to the formation of all required functionalities for total syntheses of ergot alkaloids. The strategy not only offers first total syntheses of ergot alkaloids, festuclavine (1 c), and pyroclavine (1 e), and but also an efficient and general approach to other congeners such as, lysergol (1 b), and isolysergol (1 d).

Enantioselective Synthesis of Pyrrolidines with Vicinal Stereocenters

Enantioselective Synthesis of Pyrrolidines with Vicinal Stereocenters

Control of Vicinal Stereocenters through Nickel-Catalyzed Alkyl-Alkyl Cross-Coupling.

Vicinal stereocenters are found in many natural and unnatural compounds. Although metal-catalyzed cross-coupling reactions of unactivated alkyl electrophiles are emerging as a powerful tool in organic synthesis, there have been virtually no reports of processes that generate, much less control, vicinal stereocenters. In this investigation, we establish that a chiral nickel catalyst can mediate doubly stereoconvergent alkyl-alkyl cross-coupling, specifically, reactions of a racemic pyrrolidine-derived nucleophile with cyclic alkyl halides (as mixtures of stereoisomers) to produce vicinal stereocenters with very good stereoselectivity.

Control of Vicinal Stereocenters through Nickel‐Catalyzed Alkyl–Alkyl Cross‐Coupling

AbstractVicinal stereocenters are found in many natural and unnatural compounds. Although metal‐catalyzed cross‐coupling reactions of unactivated alkyl electrophiles are emerging as a powerful tool in organic synthesis, there have been virtually no reports of processes that generate, much less control, vicinal stereocenters. In this investigation, we establish that a chiral nickel catalyst can mediate doubly stereoconvergent alkyl–alkyl cross‐coupling, specifically, reactions of a racemic pyrrolidine‐derived nucleophile with cyclic alkyl halides (as mixtures of stereoisomers) to produce vicinal stereocenters with very good stereoselectivity.

Ir/PTC cooperatively catalyzed asymmetric umpolung allylation of α-imino ester enabled synthesis of α-quaternary amino acid derivatives bearing two vicinal stereocenters.

A novel Ir/PTC (phase-transfer catalyst) cooperatively catalyzed asymmetric umpolung allylation of simple α-imino esters is developed and it provides facile access to α-quaternary amino acid derivatives bearing two vicinal stereocenters. Both the metal catalyst and the phase-transfer catalyst are crucial for this methodology. The reaction features good yields, high diastereo- and enantio-selectivities, ease of scale-up to gram scale and further transformation of the products (e.g. to quaternary proline analogues with multi stereocenters).

Palladium-Catalyzed Enantioselective Heck Alkenylation of Trisubstituted Allylic Alkenols: A Redox-Relay Strategy to Construct Vicinal Stereocenters.

An enantioselective, redox-relay Heck alkenylation of trisubstituted allylic alkenol substrates has been developed. This process enables the construction of vicinal stereocenters in high diastereo- and enantioselectivity and allows the formation of enolizable α-carbonyl methyl-substituted stereocenters with no observed epimerization under the reported reaction conditions.

Expedient and modular access to 2-azabicyclic architectures by iron-catalyzed dehydrative coupling of alcohol-bearing allylic lactams.

A high-yielding, cost-effective, modular and environmentally benign approach to [5,5]- or [6,5]-2-azabicyclic architectures bearing vicinal stereocenters, by Fe-catalyzed intramolecular dehydrative coupling of readily affordable alcohol-bearing allylic lactams is presented.

Diastereoselective Synthesis of γ-Substituted 2-Butenolides via (CDC)-Rh-Catalyzed Intermolecular Hydroalkylation of Dienes with Silyloxyfurans.

Catalytic intermolecular hydroalkylation of dienes with silyloxyfuran nucleophiles is reported. Reactions are catalyzed by 5 mol % of a (CDC)-Rh complex and proceed in up to 87% yield and 6:1 dr (syn/anti) to provide allylic butenolides bearing vicinal stereocenters. Reactions proceed with terminal aryl and alkyl dienes and with modified silyl enol ether nucleophiles including a thiophenone variant. Utility of the products is demonstrated in the synthesis of a polypropionate anti,syn-stereotriad.

Diastereoselective Pd(II)-Catalyzed sp3 C-H Arylation Followed by Ring Opening of Cyclopropanecarboxamides: Construction of anti β-Acyloxy Carboxamide Derivatives.

The diastereoselective Pd(OAc)2-catalyzed, bidentate ligand-directed sp3 C-H activation/arylation followed by ring opening of cyclopropanecarboxamides, which were assembled from cyclopropanecarbonyl chlorides and bidentate ligands (e.g., 8-aminoquinoline and 2-(methylthio)aniline), has been investigated. The treatment of various cyclopropanecarboxamides with excess amounts of aryl iodides in the presence of the Pd(OAc)2 catalyst, AgOAc and AcOH directly afforded the corresponding multiple β-C-H arylated open-chain carboxamides (anti β-acyloxy amides). This method has led to the construction of several anti β-acyloxy amides that possess vicinal stereocenters with a high degree of stereocontrol with the formation of a new C-O bond and three new C-C bonds. A plausible mechanism for the formation of multiple β-C-H arylated open-chain carboxamides from the Pd-catalyzed, bidentate ligand-directed β-C-H arylation and the ring opening of cyclopropanecarboxamides is proposed based on several control experiments. The observed diastereoselectivity and anti stereochemistry of the β-acyloxy amides were ascertained based on X-ray structural analysis of representative β-acyloxy amides.

Practical Total Syntheses of Acromelic Acids A and B.

Practical total syntheses of acromelic acids A (1) and B (2), which were scarce natural products isolated from toxic mushroom by Shirahama and Matsumoto, were accomplished in 13 (36% total yield) and 17 steps (6.9% total yield), respectively, from 2,6-dichloropyridine (8). Beginning with regioselective transformation of symmetric 8 by either ortho-lithiation or bromination, nitroalkenes 15 and 16 were provided. Stereoselective construction of the vicinal stereocenters at the C-3, 4 positions of 1 and 2 was performed by a Ni-catalyzed asymmetric conjugate addition of α-ketoesters to the nitroalkenes. Construction of the pyrrolidine ring was accomplished in a single operation via a sequence consisting of reduction of the nitro group, intramolecular condensation with the ketone, and reduction of the resulting ketimine.

Enantio- and diastereoselective polymerization: asymmetric allylic alkylation catalyzed by a planar-chiral Cp′Ru complex

In this study, we examined the regio-, diastereo-, and enantioselective polymerization using asymmetric allylic alkylation catalyzed by a planar-chiral cyclopentadienyl-ruthenium (Cp′Ru) complex ((S)-1).

ChemInform Abstract: Trapping of Carbolithiation‐Derived Tertiary Benzylic α‐Lithio Piperidines with Carbon Electrophiles: Controlling the Formation of α‐Amino Quaternary and Vicinal Stereocenters.

AbstractThe carbolithiation of 2‐aryl N‐Boc‐piperidines (I) followed by quenching with MeOH gives rise to 3‐alkylated trans‐products with high diastereoselectivity.

Synthesis of the C13–C29 fragment of leiodolide A: allylic asymmetric induction on the stereochemical course of iodolactonization

A stereocontrolled synthesis of the C13–C29 segment of leiodolide A is described. This natural product was isolated from the deep-water marine sponge Leiodermatium. A highly selective Stille cross-coupling was employed to assemble the (Z,E)-diene bearing the C15 allylic alcohol, which was followed by iodolactonization to introduce C16–C17 vicinal stereocenters. The stereochemical course of iodolactonization that is based on the solid mechanistic underpinnings arising from allylic asymmetric induction is also discussed.

ChemInform Abstract: Enantio‐ and Diastereoselective Asymmetric Allylic Alkylation Catalyzed by a Planar‐Chiral Cyclopentadienyl Ruthenium Complex.

AbstractThe mild reaction conditions result in the formation of chiral diketones having two vicinal stereocenters.

A concise synthetic route to the stereotetrad core of the briarane diterpenoids.

A concise synthesis (under 10 steps) of the stereotetrad core of the briarane diterpenoids is reported. This approach harnesses the unique reactivity of salicylate ester derived 2,5-cyclohexadienones to quickly build complexity. In particular, a highly diastereoselective acetylide conjugate addition/β-ketoester alkylation sequence was used to set the relative configuration of the C1 (quaternary) and C10 (tertiary) vicinal stereocenters. The sterochemical outcome of the β-ketoester alkylation appears to be governed by torsional steering in the transition state.

ChemInform Abstract: Highly Diastereo‐ and Enantioselective Copper‐Catalyzed Propargylic Alkylation of Acyclic Ketone Enamines for the Construction of Two Vicinal Stereocenters.

AbstractA highly diastereo‐/enantioselective construction of two vicinal chiral centers via the copper‐catalyzed propargylic alkylation of acyclic ketone enamines with propargylic esters by using a bulky and structurally rigid tridentate ketimine P,N,N‐ligand is developed.

Trapping of carbolithiation-derived tertiary benzylic α-lithio piperidines with carbon electrophiles: Controlling the formation of α-amino quaternary and vicinal stereocenters.

The interception of carbolithiation-derived tertiary benzylic α-lithio piperidines with carbon electrophiles, under HMPA-mediated conditions, has led to the diastereoselective synthesis of vicinally functionalized piperidines bearing α-amino quaternary stereocenters.