Vicinal Quaternary Carbon Centers Research Articles

Highly diastereoselective Claisen rearrangement leading to vicinal quaternary carbons construction of oxindoles

An efficient approach to spirocyclic oxindole architecture with vicinal quaternary carbon centers is described. The reaction of 2-allyloxyindolin-3-ones with cyanomethylphosphonate at low reaction temperature proceeds smoothly with consecutive olefination, isomerization, deacylation, and anion-accelerated Claisen rearrangement to give the 3,3-disubstituted oxindoles with vicinal quaternary all-carbon centers in high yield and diastereoselectivity. The oxindoles are readily converted into more synthetically advanced spiro-products.

L-Proline-Catalyzed Asymmetric Michael Addition of 2-Oxindoles to Enones: A Convenient Access to Oxindoles with a Quaternary Stereocenter

A new organocatalytic approach for 1,4-conjugate addition of 2-oxindoles to α,β-unsaturated ketones using the combination of readily available and nonexpensive l-proline and achiral trans-2,5-dimethylpiperazine as catalytic system is provided. The reaction results in oxindole derivatives with vicinal quaternary and tertiary carbon centers in up to 99% yield and 91% ee.

Organocatalytic and Electrophilic Approach to Oxindoles with C3-Quaternary Stereocenters

A Lewis base-catalyzed asymmetric allylic alkylation of Morita-Baylis-Hillman carbonates derived from isatins has been investigated, which provides an electrophilic pathway to access oxindoles bearing C3-quaternary stereocenters. Excellent diastereoselectivity and high enantioselectivity have been obtained in the vinylogous functionalization of α,α-dicyanoolefin nucleophiles, giving multifunctional products with vicinal quaternary and tertiary chiral carbon centers.

Trapping of an Ammonium Ylide with Activated Ketones: Synthesis of β-Hydroxy-α-Amino Esters with Adjacent Quaternary Stereocenters

A novel Rh2(OAc)4-catalyzed three-component reaction of diazoacetates, anilines, and activated ketones via ammonium ylide trapping processes is reported. The reaction of isatins afforded α-amino-β-hydroxy esters bearing the 3-substituted 3-hydroxyindolin-2-one moiety with vicinal quaternary carbon centers in one step with high chemo- and diastereoselectivity. Extension of the reaction to acyclic α-keto esters afforded 2-hydroxy-2-alkyl-3-aryl-3-(phenylamino) succinates in moderate yield and diastereoselectivity.

Extending Pummerer reaction chemistry. Examination of the prospects for forming vicinal quaternary carbon centers

Pummerer chemistry applied to 2-sulfinyl indoles promotes oxidative cyclization of pendant nucleophiles to furnish C(3) spirocyclic indolenine products. Use of tetrasubstituted silyl enol ether nucleophiles in this transform yields spirocycles featuring vicinal all-carbon quaternary centers in two cases, but fails when a nearby amine can intervene.

PdII‐Catalyzed Asymmetric Addition Reactions of 1,3‐Dicarbonyl Compounds: Mannich‐Type Reactions with N‐Boc Imines and Three‐Component Aminomethylation

This paper describes catalytic asymmetric Mannich-type reactions of beta-ketoesters and malonates using chiral palladium complexes. Although readily enolizable, carbonyl compounds are attractive substrates, the use of such compounds as nucleophiles in Mannich-type reactions has not been extensively investigated. In the presence of chiral Pd aqua complexes (2.5 mol %), beta-ketoesters reacted with various N-Boc imines (Boc=tert-butoxycarbonyl) to afford the desired beta-aminocarbonyl compounds in good yield with high to excellent stereoselectivity (up to 96:4 d.r., 95-99 % ee in most cases). In these reactions, construction of highly crowded vicinal quaternary and tertiary carbon centers was achieved in one step. A chiral Pd enolate is considered to be the key intermediate. To elucidate the stereoselectivity observed in the reaction, possible transition-state models are discussed, taking into account steric and stereoelectronic effects. Furthermore, this catalytic system was applied to the Mannich-type reaction of malonates with N-Boc imine as well as one-pot classical aminomethylation of beta-ketoesters using benzylamine salt and formalin. The reactions proceeded smoothly, and the corresponding Mannich products were obtained in high yield with moderate to good enantioselectivity.

Palladium-catalyzed regio- and diastereo-selective allylic alkylation using 2-(diphenylphosphino)benzoic acid: construction of vicinal quaternary and tertiary carbon centers

The palladium-catalyzed regio- and diastereo-selective allylic alkylation of allyl acetates with carbon nucleophiles occurred. The stereochemistry was highly controlled by the palladium catalyst with 2-(diphenylphosphino)benzoic acid as the ligand, and vicinal quaternary and tertiary carbon centers were constructed.

Synthetic Studies on Perophoramidine and the Communesins: Construction of the Vicinal Quaternary Stereocenters.

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Synthetic Studies on Perophoramidine and the Communesins: Construction of the Vicinal Quaternary Stereocenters

An efficient synthetic strategy for installation of the two vicinal quaternary carbon centers of the communesins is reported. Key steps include the O-allylation/Claisen rearrangement of spirolactone systems, which are formed by tandem intramolecular Heck cyclization/carbonylation. Substituent and solvent effects on the stereochemical outcome of the Claisen rearrangements have been examined. The stereochemical assignment of the allyl spirolactone previously reported as 17 has now been revised to 31, which has the communesin relative configuration at the quaternary carbons. Key C-allyl spirolactone 59 bearing functional handles required for the communesin core has been constructed with a 9.8:1 diastereomer ratio.

Enantio‐ and Diastereoselective Construction of Vicinal Quaternary and Tertiary Carbon Centers by Catalytic Michael Reaction of α‐Substituted β‐Keto Esters to Cyclic Enones.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Stereocontrolled Synthesis of Angularly Substituted 1‐Azabicyclic Rings by Cationic 2‐Aza‐Cope Rearrangements.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Enantio- and diastereoselective construction of vicinal quaternary and tertiary carbon centers by catalytic Michael reaction of α-substituted β-keto esters to cyclic enones

A catalytic enantio- and diastereoselective Michael reaction was achieved to construct vicinal quaternary and tertiary carbon centers in one step. Using 5 mol % of La(O- i-Pr) 3 and 10 mol % of a new N-linked-BINOL type ligand, the reaction of α-substituted β-keto esters to cyclic enones provided the corresponding Michael adducts in up to quantitative yield with a diastereomeric ratio up to 86/14 and enantiomeric excess up to 86% for the major isomer. An alternative catalyst preparation method using La(OTf) 3 instead of La(O- i-Pr) 3 was also examined.

Stereocontrolled Synthesis of Angularly Substituted 1-Azabicyclic Rings by Cationic 2-Aza-Cope Rearrangements

A new synthesis of 1-azabicyclic molecules having angular substitution is reported. This method can be employed to prepare a range of 1-azabicylic rings, including ones containing vicinal quaternary carbon centers and three contiguous stereocenters. [structure: see text]

Enantioselective Synthesis of (‐)‐Idiospermuline.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Enantioselective synthesis of (−)-idiospermuline

The enantioselective total synthesis of the nonacyclic polypyrrolidinoindoline (−)-idiospermuline is described. Stereocontrolled formation of the vicinal quaternary carbon centers is achieved in a single step by dialkylation of an unsymmetrical prostereogenic dienolate with a tartrate-derived chiral dielectrophile. A catalyst-controlled diastereoselective Heck cyclization is employed to form the diaryl-substituted quaternary center.

Total Syntheses of (−)-Herbertenediol, (−)-Mastigophorene A, and (−)-Mastigophorene B. Combined Utility of Chiral Bicyclic Lactams and Chiral Aryl Oxazolines

A nonracemic bicyclic lactam has been used to construct a chiral cyclopentane containing vicinal quaternary carbon centers in optically pure form, which is common to all of the title compounds. An oxazoline-mediated asymmetric Ullmann coupling was then utilized to establish chirality about the biaryl axis of mastigophorenes A and B. Through the course of this synthesis, it was clearly demonstrated that smaller chiral auxiliaries lead to higher levels of atroposelection, a previously unknown phenomenon of the asymmetric Ullmann coupling.

Application of the Ester Enolate Claisen Rearrangement in the Synthesis of Amino Acids Containing Quaternary Carbon Centers.

Ester enolate Claisen rearrangement of highly substituted amino acid allylic esters 4 allows for the synthesis of sterically demanding amino acids 5 with beta-quaternary carbon centers. Because of enolate fixation by chelation, the rearrangement occurs in a highly diastereoselective fashion. The methodology is suitable not only for glycine derivatives but also for allylic esters of various amino acids. In this case amino acids with two vicinal quaternary carbon centers are created. With unsymmetrically substituted allylic esters like 4k-n the rearrangement proceeds with a high degree of diastereoselectivity.