α‑Quaternary Proline Derivatives by Intramolecular Diastereoselective Arylation of <i>N</i>‑Carboxamido Proline Ester Enolates

Pyrrolidine-2-carboxylate esters substituted in the 3-, 4- or 5-positions were converted to their <i>N</i>′-aryl urea derivatives. Deprotonation at the 2-position to form a potassium enolate led to migration of the <i>N</i>′-aryl substituent to the 2 position of the pyrrolidine ring, followed by cyclization of the resulting urea to give bicyclic α-aryl hydantoin derivatives of substituted prolines. Depending on the substitution pattern of the starting material, high diastereoselectivity was observed in the aryl migration, allowing formation of the products in enantiomerically enriched form, despite the intermediacy of a planar enolate. The hydrolysis of the bicyclic hydantoins under basic conditions gave a range of enantiopure and enantioenriched quaternary α-aryl proline derivatives

Tertiary Alcohols by Tandem β-Carbolithiation and N→C Aryl Migration in Enol Carbamates

Enol carbamates (<i>O</i>-vinylcarbamates) derived from aromatic or α,β-unsaturated compounds and bearing an <i>N</i>-aryl substituent undergo carbolithiation by nucleophilic attack at the (nominally nucleophilic) β position of the enol double bond. The resulting carbamate-stabilized allylic, propargylic, or benzylic organolithium rearranges with N→C migration of the N-aryl substituent, creating a quaternary carbon α to O. The products may be readily hydrolyzed to yield multiply branched tertiary alcohols in a one-pot tandem reaction, effectively a polarity-reversed nucleophilic β-alkylation–electrophilic α-arylation of an enol equivalent

Spirocyclic Dihydropyridines by Electrophile-Induced Dearomatizing Cyclization of N‑Alkenyl Pyridinecarboxamides

On treatment with acylating or sulfonylating agents, <i>N</i>-alkenyl pyridine carboxamides (<i>N</i>-pyridinecarbonyl enamines) undergo a dearomatizing cyclization initiated by pyridine acylation and followed by intramolecular trapping of the resulting pyridinium cation. The products are spirocyclic dihydropyridines which may be further elaborated to spirocyclic heterocycles with drug-like features

Spirocyclic Dihydropyridines by Electrophile-Induced Dearomatizing Cyclization of N‑Alkenyl Pyridinecarboxamides

On treatment with acylating or sulfonylating agents, <i>N</i>-alkenyl pyridine carboxamides (<i>N</i>-pyridinecarbonyl enamines) undergo a dearomatizing cyclization initiated by pyridine acylation and followed by intramolecular trapping of the resulting pyridinium cation. The products are spirocyclic dihydropyridines which may be further elaborated to spirocyclic heterocycles with drug-like features

Structural Influences in Lithium Pentadienylsilane Complexes

Structurally characterized lithium pentadienyls are very rare. We report the molecular structures of two lithium pentadienyls, [(pmdeta)­Li­{1-(R₃Si)­C₅H₆}] (<b>3</b>) and [(pmdeta)­Li­{1,5-(R₃Si)₂C₅H₅}] (<b>4</b>) (R₃Si = Me₂(NMe₂)­Si, pmdeta = <i>N</i>,<i>N</i>,<i>N</i>′,<i>N</i>″,<i>N</i>″-pentamethyldiethylenetriamine). In <b>3</b>, the pentadienyl carbons adopt an η³ coordination mode, whereas in <b>4</b> η¹ coordination is found. The origins of the different coordination modes are discussed

Structural Influences in Lithium Pentadienylsilane Complexes

Structurally characterized lithium pentadienyls are very rare. We report the molecular structures of two lithium pentadienyls, [(pmdeta)­Li­{1-(R₃Si)­C₅H₆}] (<b>3</b>) and [(pmdeta)­Li­{1,5-(R₃Si)₂C₅H₅}] (<b>4</b>) (R₃Si = Me₂(NMe₂)­Si, pmdeta = <i>N</i>,<i>N</i>,<i>N</i>′,<i>N</i>″,<i>N</i>″-pentamethyldiethylenetriamine). In <b>3</b>, the pentadienyl carbons adopt an η³ coordination mode, whereas in <b>4</b> η¹ coordination is found. The origins of the different coordination modes are discussed

Tertiary Thiols from Allylic Thiocarbamates by Tandem Enantioselective [3,3]-Sigmatropic Rearrangement and Stereospecific Arylation

The synthesis of tertiary thiols in enantiomerically enriched form is accomplished by lithiation of enantiomerically enriched <i>N</i>-aryl allylic thiocarbamates. Formation of an allyllithium derivative promotes intramolecular N to C aryl migration to the position α to sulfur, generally with good stereospecificity. The substrates may themselves be obtained by Pd-catalyzed enantioselective [3,3]-sigmatropic rearrangement of <i>N</i>-aryl <i>O</i>-allyl thiocarbamates. Solvolysis of the product thiocarbamates yields tertiary thiols, which may be converted to sulfide derivatives

Manipulating the Diastereoselectivity of Ortholithiation in Planar Chiral Ferrocenes

The sense of asymmetric ortholithiation directed by a chiral oxazoline may be inverted simply by the choice of achiral ligand. Comparison of results with a number of ferrocenyl oxazoline derivatives suggests that lithiation takes place by coordination to the oxazoline nitrogen irrespective of the ligand used

Synthesis of 1‑Arylcycloalkenamines by Intramolecular Arylation of Lithiated Ureas

The deprotonation of <i>N</i>′-arylurea derivatives of cyclohexenamines by alkyllithiums leads to migration of the <i>N</i>′-aryl substituent from N′ to the allylic position α to N via rearrangement of a urea-stabilised allyllithium intermediate. The product ureas may be solvolysed to reveal 1-arylcyclohexenamines

Palladium Catalyzed C‑Arylation of Amino Acid Derived Hydantoins

Palladium­(II) trifluoroacetate (5 mol %) catalyzes the C-arylation of <i>N,N</i>-disubstituted hydantoins by aryl iodides in good yield. The reaction proceeds through base-promoted enolization of the amino acid derived hydantoins, and the resulting 5,5-disubstituted hydantoins may be deprotected at one or both N atoms to yield biologically active structures or alternatively hydrolyzed to the parent α-aryl α-amino acids. The reaction is successful with a variety of parent amino acids and a range of electron-rich and electron-poor aryl iodides