Diego Savoia

Catalytic asymmetric syntheses of secondary alcohols using cis-1-amino-2-indanols as chiral ligands

Abstract Both enantiomers of cis-1-amino-2-indanols (1a,b) have been used as chiral ligands in the catalytic asymmetric reduction of ketones with BH3·SMe2 affording secondary alcohols with enantiomeric excesses up to 95%. Furthermore, some N,N-diakyl derivatives of 1a,b catalyzed the enantioselective addition of diethylzinc to aldehydes.

Diastereoselective allylation of chiral imines. Novel application of allylcopper reagents to the enantioselective synthesis of homoallyl amines

Abstract The addition of allylcopper reagents to imines derived from S-valine occurs with excellent diastereoselectivity (e.e. 98 %).

Nickel-catalyzed coupling of activated alkenes with organic halides

Abstract Alkenenickel complexes catalyze the coupling of activated olefins with aryl or vinyl halides. Substitution or conjugate-addition products are obtained depending on the activating group in the alkene and on the nature of the organic halide.

DIASTEREOSELECTIVE ADDITION OF METHYLLITHIUM AND DIMETHYLCUPRATE-BORON TRIFLUORIDE TO IMINES DERIVED FROM (S)-1-PHENYLETHYLAMINE

Abstract The reactions of dimethylcuprate-boron trifluoride reagents with the imines derived from (S)-1-phenylethylamine afforded the secondary amines by addition to the Si face of the imines. (S,S)-bis(1-phenylethyl)amine and (S)-1-cyclohexylethanamine were prepared with high stereoselectivity, in the latter case by a two step sequence involving the final cleavage of the auxiliary. Methyllithium attacked mainly the Si face of the imines derived from 4-pyridine carboxaldehyde and 2-methoxybenzaldehyde, but the Re face of the imines derived from 2-pyridine and 2-furan carboxaldehyde.

Highly reactive metals from potassium—graphite. Preparation and use of titanium—graphite and tin—graphite

Abstract The potassium—graphite route to active forms of metals has been extended to the preparation of titanium—graphite (TiGr) and tin—graphite (SnGr). The TiGr is used to achieve the reductive coupling of ketones to give alkenes, and SnGr is used in the preparation of diallyltin dibromide complexes which react with aldehydes to give homoallylic alcohols.

Creating Chemical Diversity in Indole Compounds by Merging Au and Ru Catalysis

Sequential dual‐metal catalyzed reactions are successfully applied to create chemical diversity in indole polycyclic alkaloids. Gold‐catalyzed intramolecular allylic alkylation of indoles with alcohols, followed by Ru‐assisted ring‐closing metathesis opens up access to a large variety of functionalized tetrahydrocarbazoles and tetrahydro‐β‐carbolines in a straightforward manner. The gold‐catalyzed alkylation allows complex molecular architectures to be realized in a highly regio‐ and stereocontrolled manner.

Asymmetric synthesis of 8-aminoindolizidine from chiral 2-pyrroleimines.

1-Allyl-2-pyrroleimines obtained from (S)-valinol and (S)-phenylglycinol underwent highly diastereoselective addition of allylmagnesium chloride, used in excess amounts, to give the corresponding secondary amines with concomitant allyl to (Z)-1-propenyl isomerization of the 1-pyrrole substituent. Transformation of the 2-amino alcohol moiety to an oxazolidinone, or its cleavage and subsequent N-protection, followed by ring-closing metathesis of the two alkene groups gave the unsaturated bicyclic compound. Full hydrogenation of the alkene function and the aromatic rings afforded the indolizidine derivative as a mixture of two or three diastereomers with a ratio which was dependent on the nature of both the N-substituent and the catalyst. The two prevalent diastereomers were isolated, and their configuration was determined by X-ray crystallographic analysis.

Reductive amination of 1,4- and 1,5-dicarbonyl compounds with (S)-valine methyl ester. Synthesis of (S)-2-phenylpyrrolidine and (S)-2-phenylpiperidine

Abstract The reductive amination of 4-phenyl-4-oxobutanal and 5-phenyl-5-oxopentanal with (S)-valine methyl ester and sodium cyanoborohydride afforded the N-substituted (S)-2-phenylpyrrolidine (88% d.e.) and (S)-2-phenylpiperidine (96% d.e.), from which the levorotatory NH cyclic amines were obtained. On the other hand, the analogous reductive amination of simple ketones, 2,5 hexanedione, and 2,6-heptanedione was poorly selective.

Diastereoselective addition of methylcopper- and diemthylcuprate-boron trifluoride reagents to (S)-(N-alkylidine)-1-phenylethylamines

Abstract The reactions of methylcopper- and diemthylcuprate-boron trifluoride reagents with aldimines derived from (S)-1-phenylethylamine afford with good diastereoselectivity (S,S)-amines from aromatic imines, but the (R,S)-amine from an aliphatic imine.

Design and synthesis of enantiopure 1-[1(S)-(2-pyridyl)alkyl]-2(R)-isopropylaziridines, new ligands for asymmetric catalysis

Abstract Enantiopure 1-(2-pyridyl)alkyl aziridines were designed as bidentate ligands for asymmetric catalysis. Their synthesis involved the addition of organometallic reagents to the imine prepared from 2-pyridinealdehyde and an enantiopure β-aminoalcohol, followed by cyclisation of the β-aminoalcohol moiety to the aziridine ring. Two such ligands (N–N)* were prepared from ( S )-valinol and converted to the complexes (η 3 -allyl)(N–N)*Pd + SbF 6 − , one of which was characterised by X-ray crystallography. Modest enantioselectivities were achieved in a representative Pd-catalysed allylic substitution reaction.