A synthesis of (+/-)-sparteine

(+/-)-Sparteine has been synthesised with stereochemistry controlled in such a way as to make the route amenable to an efficient synthesis of either enantiomer.     

A synthesis of (+/-)-sparteine

In a synthesis of racemic sparteine, Diels-Alder reaction between dimethyl bromomesaconate 14 and dicyclopentenyl 4, followed by cyclopropane formation, set up the stereochemistry at C-1 and C-5 as S and R, respectively, in a meso intermediate 8. The stereochemistry at C-2 and C-4 was then secured by a moderately diastereoselective protonation of the bis-enolate 17 derived from the diester 8 by reductive cleavage with lithium in liquid ammonia. The C=C in the racemic diester 19 was ozonolysed and the diketone converted by Beckmann rearrangement into the bis-lactam . Reduction of the bis-lactam with lithium aluminium hydride and intramolecular nucleophilic displacement gave racemic sparteine 1. Some ideas for making this synthesis amenable to a synthesis of enantiomerically enriched sparteine are presented.     

Enantioselective organocatalytic Michael addition reactions between N-heterocycles and nitroolefins

[reaction: see text] A method for Michael addition of N-heterocycles to nitroolefins has been developed. The process is promoted by a cinchona alkaloid derivative to give Michael adducts in moderate to high enantioselectivities.     

Enantioselective nitroaldol (Henry) reaction using copper(II) complexes of (-)-sparteine

The dichloro[(-)-sparteine-N,N']copper(II) complex provides Henry adducts with high enantioselectivities (73-97% ee) in Henry reaction between nitromethane and various aldehydes.     

Concise asymmetric synthesis of (-)-sparteine

A six-step asymmetric synthesis of natural (-)-sparteine from ethyl 7-iodohept-2-enoate is reported, involving a connective Michael addition of an amino ester-derived enolate to an alpha,beta-unsaturated amino ester.     

Asymmetric alkylation of diphenylmethane derivatives using (−)-sparteine

Alkylation of 2-oxygenated diphenylmethane derivatives using sec-butyllithium and (−)-sparteine gave enantiomeric excesses of up to 60% with allyl bromide but alkylations with methyl electrophiles were poorly selective. When compounds with a free hydroxy in the 2-position were alkylated the selectivity was reversed.     

A formal total synthesis of (+/-)-cephalotaxine using sequential N-acyliminium ion reactions

[reaction: see text] Novel synthesis of cephalotaxine 1 based on tertiary N-acyliminium ion chemistry starting from alkynylamide 2 was achieved. The key steps include the preparation of pyrroloisoquinoline 4 from alkynylamide 2, the ring expansion of pyrroloisoquinoline 4 to pyrrolobenzazepine 12, and the construction of cyclopentapyrrolobenzazepine ring system 6, all of which are derived from N-acyliminium ion intermediates.     

Enantioselective catalysis by metal complexes. 5. Asymmetric hydrosilylation using the phosphine complex [Rh(COD)Cl]2/(S)-Phephos

The complex [Rh(COD)Cl]₂/(S)-Phephos is demonstrated to be highly active and enantioselective in model hydrosilylation of acetophenone by diphenylsilane. The enantioselectivity increases as the reaction temperature increases. This allows the reaction to be carried out at acetophenone/Rh ratios up to 20,000. A mathematical model of the reaction using Rh/(S)-Phephos is constructed.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 9, pp. 1951–1955, September, 1990.     

The crystal structures of the chiral alkyllithium bases [n-BuLi.(-)-sparteine]2 and [Et2O.(i-PrLi)2.(-)-sparteine

The crystal structures of the two chiral alkyllithium bases [n-BuLi.(-)-sparteine]2 (1) and [Et2O.(i-PrLi)2.(-)-sparteine] (2) have been determined. For compound 1, a symmetric dimer is observed in the solid state, with two (-)-sparteine ligands coordinating to the lithium centers. Because of steric reasons, compound 2 crystallizes as an unsymmetric dimer with the four methyl groups pointing away from the sterically demanding (-)-sparteine ligand. Compound 2 contains one four-coordinate lithium center [coordinated to (-)-sparteine] and one three-coordinate lithium center (coordinated to Et2O). As a result of this arrangement, significantly different Li-C distances are found in the central four-membered ring of compound 2.     

Asymmetric Catalysis. Part 149 [1]. Synthesis of New Chiral Tridentate Ligands for Enantioselective Catalysis

Summary. The synthesis of new chiral tridentate ligands is reported which coordinate transition metals in a meridional way. The ligands contain a pyridine ring, an oxazoline ring, and a strongly coordinating diphenylphosphanyl group. The methionine-derived ligand forms a copper complex, which has been studied by X-ray crystallography. The new ligands were tested in models of enantioselective catalyses, such as hydrogenation of ketopantolactone, hydrosilylation of acetophenone, and transfer hydrogenation of acetophenone.X-ray structure analysesReceived March 4, 2003; accepted March 4, 2003 Published online August 18, 2003     

Enantioselective carbanion cyclization of 5-alkenyl carbamates induced by asymmetric lithiation with s-butyllithium/(−)-sparteine system

Treatment of (E)-6-phenyl-5-hexenyl carbamates with s-BuLi/(−)-sparteine is shown to afford the trans-1,2-disubstituted cyclopentane derivatives in high % ee, along with the bicyclo[3.1.0]hexanes (bicyclization products).     

Condensation of laterally lithiated o-methyl and o-ethyl benzamides with imines mediated by (-)-sparteine. Enantioselective synthesis of tetrahydroisoquinolin-1-ones

The first asymmetric synthesis of tetrahydroisoquinolin-1-ones using a (-)-sparteine-mediated lateral metalation-imine addition sequence to furnish 3-phenyl tetrahydroisoquinolinones 3a with enantioselectivities up to 81% ee is described (Scheme 4). For amide 7b, imine addition products 10 and 11 have been obtained with high diastereoselectivities (91-97% de) and enantioselectivities (91-98% ee) (Scheme 8).     

Asymmetric synthesis of 6-alkyl- and 6-arylpiperidin-2-ones. Enantioselective synthesis of (S)-(+)-coniine

A variety of diolefinic hydrazides (1) have been assembled in a highly diastereoselective manner by addition of allyllithium to chiral SAMP hydrazones followed by N-acylation with acryloyl chloride. Substrates 1 undergo ring-closing metathesis to give the cyclic enehydrazides (5) which can be easily converted into virtually enantiopure 6-alkyl- or 6-arylpiperidin-2-ones (7). The versatility of this hydrazone addition-RCM protocol has been further exemplified by the conversion of the unsaturated heterocycle 5b into the piperidine alkaloid (S)-(+)-coniine.     

Enantioselective synthesis of (-)-pentalenene

A short, enantioselective synthesis of (-)-pentalenene is described. Catalytic enantioselective cyclopropenation with (R,R)-Rh2(OAc)(DPTI)3 was used to set the absolute stereochemistry, and an intramolecular Pauson-Khand reaction of the resulting cyclopropenyne was used to establish the quaternary center.     

Enantioselective synthesis of (-)-paeonilide

The first enantioselective synthesis of (-)-paeonilide is reported. Starting from inexpensive furan-3-carboxylic acid the targeted monoterpene was obtained in 12 steps via an asymmetric cyclopropanation-lactonization cascade and a stereoselective side chain insertion at an acetal-like position.     

Enantioselective synthesis of allylic alcohols by the sequential aminoxylation-olefination reactions of aldehydes under ambient conditions

A novel, highly enantioselective synthesis of O-amino-substituted allylic alcohols by the sequential asymmetric alpha-aminoxylation/Wadsworth-Emmons-Horner olefination reactions of aldehydes is presented.     

Enantioselective Catalysis. Part 156 [1]. Ruthenium Procatalysts and 2-Pyridinealdehyde/( S)- NOBIN-Derived Cocatalysts in the Transfer Hydrogenation of Acetophenone with 2-Propanol

Several ruthenium procatalysts were tested in the transfer hydrogenation of acetophenone with 2-propanol using the chiral imine ligand (S)-2-(2-pyridinylmethyleneamino)-2-hydroxy-1,1-binaphthyl and the corresponding amine (S)-2-(2-pyridinylmethylamino)-2-hydroxy-1,1-binaphthyl. Ru(PPh ₃)₃Cl₂ was the best procatalyst. Its triphenylphosphane ligands were crucial for the catalytic activity and take part in the chirality transfer. Triphenylphosphane removing reagents such as copper(I) chloride, TEMPO, or TMAO improved the catalytic performance to enantioselectivities up to 99% ee. The findings led to a mechanistic proposal including dissociation equilibria of triphenylphosphane and chelate ring opening of the tridentate chiral binaphthyl ligand. New ligands with an additional chiral center were synthesized and tested as cocatalysts. The nature of catalytically active intermediates was examined by MS and NMR spectroscopy.     

Enantioselective synthesis of (-)-codeine and (-)-morphine

A new synthetic strategy for the synthesis of the opiate and amaryllidaceae alkaloids emerges employing a Pd-catalyzed asymmetric allylic alkylation to set the stereochemistry. The pivotal tricyclic intermediate is available in six steps from 2-bromovanillin and the monoester of methyl 6-hydroxycyclohexene-1-carboxylate, the latter available from glutaraldehyde and the Emmons-Wadsworth-Horner phosphate reagent. This intermediate requires only two steps to convert to (-)-galanthamine. Using a Heck vinylation, we found that the fourth ring of codeine/morphine is formed. The final ring formation involves a novel visible light-promoted hydroamination. Thus, six steps are required to convert the pivotal tricyclic intermediate into codeine, which has been demethylated in high yield to morphine.     

Ligand effects in the synthesis of N-heterocycles by intramolecular Heck reactions

Chemo- and regioselectivity of intramolecular Heck reactions are dependent on the type of ligand employed. Six- to eight-membered benzolactams are produced in good yields using PPh3 as ligand. In contrast, a biaryl coupling occurred preferentially under ligandless conditions to form a dihydrophenanthridine product. Conformations of the seven- and eight-membered benzolactams in the solid state were examined by X-ray crystallography.