8-Iodonaphthalene-1-carbaldehyde: A Versatile Building Block for Diversity-Oriented Synthesis.
The scarcely studied 8-halonaphthalene-1-carbaldehyde structure has been converted into the corresponding Ellman’s imine and subjected to several transformations, thus achieving an assorted library of polycyclic carbo- and heterocycles. The potential of this scaffold for Diversity-Oriented Synthesis has been shown. Most of these skeletons are unprecedented and, therefore, cover unexplored regions of the chemical space.
ChemInform Abstract: Asymmetric Allylation/Ring Closing Metathesis: One-Pot Synthesis of Benzo-Fused Cyclic Homoallylic Amines. Application to the Formal Synthesis of Sertraline Derivatives.
A stepwise process consisting of asymmetric allylation of imines of type (I) and following ring-closing metathesis of the resulting dienes (III) is developed to synthesize cyclic homoallylic amines.
ChemInform Abstract: Intramolecular Michael Reaction of tert-Butylsulfinyl Ketimines: Asymmetric Synthesis of 3-Substituted Indanones.
The reaction proceeds in the presence of the Ruppert—Prakash reagent (Tms-CF3) with either TBAT or TBAF as a base.
Base-Dependent Stereodivergent Intramolecular Aza-Michael Reaction: Asymmetric Synthesis of 1,3-Disubstituted Isoindolines
The nucleophilic addition (A(N)) / intramolecular aza-Michael reaction (IMAMR) process on Ellman's tert-butylsulfinyl imines, bearing a Michael acceptor in the ortho position, is studied. This reaction affords 1,3-disubstituted isoindolines with a wide range of substituents in good yields and diastereoselectivities. Interestingly, careful choice of the base for the aza-Michael step allows either the cis or the trans diastereoisomers to be exclusively obtained. This stereodivergent cyclization has enabled the synthesis of C2-symmetric bisacetate-substituted isoindolines. In addition, bisacetate isoindolines bearing two well-differentiated ester moieties are also noteworthy because they may a…
ChemInform Abstract: Asymmetric Synthesis of Fluorinated Isoindolinones Through Palladium-Catalyzed Carbonylative Amination of Enantioenriched Benzylic Carbamates.
The asymmetric synthesis of fluorinated isoindolinones has been achieved by a palladium-catalyzed aminocarbonylation reaction of the corresponding α-fluoroalkyl o-iodobenzylamines. A base-mediated anti β-hydride elimination process was suggested to explain the partial erosion of the optical purity observed in some cases. This mechanistic rationale enabled the minimization of this partial racemization by fine-tuning the pKa of the base.
Asymmetric Synthesis of Fluorinated Isoindolinones through Palladium-Catalyzed Carbonylative Amination of Enantioenriched Benzylic Carbamates
The asymmetric synthesis of fluorinated isoindolinones has been achieved by a palladium-catalyzed aminocarbonylation reaction of the corresponding -fluoroalkyl o-iodobenzylamines. A base-mediated anti -hydride elimination process was suggested to explain the partial erosion of the optical purity observed in some cases. This mechanistic rationale enabled the minimization of this partial racemization by fine-tuning the pK(a) of the base.
Relay Catalysis: Enantioselective Synthesis of Cyclic Benzo-Fused Homoallylic Alcohols by Chiral BrOnsted Acid-Catalyzed Allylboration/Ring Closing Metathesis
Six- and seven-membered benzo-fused cyclic homoallylic alcohols can be readily synthesized by a tandem chiral BrOnsted acid-catalyzed allyl (crotyl)boration/ring closing metathesis sequence performed under orthogonal relay catalysis conditions. Excellent enantio- and diastereoselectivities are obtained in most of the cases. In addition, the parent crotylboration/RCM process is also described. The required substrates, ortho-vinylbenzaldehydes, are readily available in one step from commercially available starting materials. Both catalysts and reactants are also available from commercial suppliers. The reaction shows broad functional group compatibility and is also suitable for heteroaromatic…
Asymmetric Allylation/Ring Closing Metathesis: One-Pot Synthesis of Benzo-fused Cyclic Homoallylic Amines. Application to the Formal Synthesis of Sertraline Derivatives
A one-pot asymmetric allylation/ring closing metathesis (RCM) sequence for the synthesis of cyclic homoallylic amines has been developed. A library of six- and seven-membered benzo-fused products has been synthesized in good yields and complete diastereoselectivity. The new methodology has been applied to the formal syntheses of the antidepressant Sertraline and the epimeric Norsertraline. The methodology is amenable for the synthesis of analogs.
Intramolecular Michael reaction of tert-butylsulfinyl ketimines: asymmetric synthesis of 3-substituted indanones.
Aromatic tert-butylsulfinyl ketimines bearing a suitable Michael acceptor at the ortho position readily undergo an intramolecular conjugate addition achieving indanone derivatives in good yields and complete diastereoselectivity.
ChemInform Abstract: Base-Dependent Stereodivergent Intramolecular Aza-Michael Reaction: Asymmetric Synthesis of 1,3-Disubstituted Isoindolines.
For the reaction of the compounds (I) the careful choice of the base allows the exclusive formation of either cis or trans diastereoisomer with the exception of the trihalogenates (Ie) and (If), which afford the cis-products regardless of the base used.
CCDC 935857: Experimental Crystal Structure Determination
Related Article: Santos Fustero, Lidia Herrera, Ruben Lázaro, Elsa Rodríguez, Miguel A. Maestro, Natalia Mateu, Pablo Barrio|2013|Chem.-Eur.J.|19|11776|doi:10.1002/chem.201301591