Pyrrolidinones chiral

S-(-)-5-HEPTYL-2-PYRROLIDINONE. CHIRAL BICYCLIC LACTAMS AS TEMPLATES FOR PYRROLIDINES AND PYRROLIDINONES (2-Pyrrolldlnone, 5-heptyl-, (S)-)... 

Recently, Akiyama et al. reported an enantiocontrolled [3+2] cycloaddition of chirally modified Fischer alkenylcarbene complexes 180 with aldimines 181 under Lewis-acid catalysis (Sn(OTf)2) to afford enantiomerically pure 1,2,5-trisubstituted 3-alkoxypyrrolines 182 (Scheme 40) [121]. The mode of formation of these products 182 was proposed to be a [4+2] cycloaddition, with the complexes 180 acting as a 1-metalla- 1,3-diene with subsequent reductive elimination. Upon hydrolysis under acidic conditions, the enol ethers give the enantiomerically pure 3-pyrrolidinones 183 (Table 9). 

Scheme 40 Synthesis of enantiomerically pure 1,2,5-trisubstituted 3-pyrrolidinones 183 from chirally modified 1-alkoxypropenylidene complexes 180 and aldimines [121]. For further details see Table 9...

The reaction of alkenylcarbene complexes and imines in the presence of a Lewis acid generates pyrroline derivatives as a result of a [3C+2S] cyclisation process [76]. This reaction has been extended to an asymmetric version by the use of chiral alkenylcarbene complexes derived from several chiral alcohols. However, the best results are found when (-)-8-phenylmenthol-derived complexes are used and catalytic amounts of Sn(OTf)2 are added to the reaction. In these conditions high levels of trans/cis selectivity are achieved and the hydrolysis of the major tram diastereoisomers allows the preparation of optically pure 2,5-disubstituted-3-pyrrolidinone derivatives (Scheme 29). 

Several chiral ligands have been developed for use with the rhodium catalysts, among them are pyrrolidinones and imidazolidinones.207 For example, the lactamate of pyroglutamic acid gives enantioselective cyclopropanation reactions. 

Substituted 3-hydroxy-2-pyrrolidinones were synthesised via 1,3-DC reactions of furfuryl nitrones with acrylates and subsequent intramolecular cyclisation after N-0 bond reduction. Addition of iV-acryloyl-(2/()-bomane-10,2-sultam to Z-nitrone 83 gave the endo/exo cycloadducts in 85 15 ratio with complete stereoface discrimination <00JOC1590>. The 1,3-DC of pyrroline A-oxide to chiral pentenoates using (-)-/rans-2-phenylcyclohexanol and (-)-8-phenylmenthol as chiral auxiliaries occurred with moderate stereocontrol (39% de and 57% de, respectively) and opposite sense of diastereoselectivity <00EJO3595>. The... 

Optically active iV-unprotected-2-pyrrolidinones 194 were obtained from selenocarboxylate or allylamine via radical cyclization and subsequent one-step cleavage of the C-O and C-N bond of the inseparable mixture of the two bicyclic oxyoxazolidinones 192 and 193 with -Bu4NF. The initial radical reaction is highly stereoselective. Products were obtained with ee up to 90%. The mandelic acid 195, which served as the chiral auxiliary in this method, was recovered with no loss of optical activity (Equation 33) <2003T6291>. 

Bicyclic alkaloids. Nagao et al. have developed a general synthesis of chiral bicyclic alkaloids with a nitrogen atom at the ring juncture, such as pyrrolizidines [5.5], quinolizidines [6.6], and indolizidines [6.5], based on a highly diastereose-lective alkylation of 3-a>-chloroacyl-(4S)-isopropyl-l,3-thiazolidine-2-thiones (1, m = 1,2) with 5-acetoxy-2-pyrrolidinone (2, n = 1) or 6-acetoxy-2-piperidinone (2, n = 2). Thus the tin enolate of 1 (m = 1), prepared with Sn(OTf) and N-... 

S(-)-5-n-Heptylpyrrolidinone. Chiral Bicyclic Lactams as Templates to Pyrrolidines and Pyrrolidinones. 

Fig. 15.2 Immobilized chiral dirhodium(ll) pyrrolidinone-carboxylates and their application to intramolecular cyciopropanation of allyl diazoacetate [40].

Pyrrolidinones with a chiral C-5 atom have been prepared in a very simple, one-pot synthesis, by treatment of TV-alkoxycarbamoyl y-amino a,/J-unsaturated carboxylates with Mg in methanol (equation 168)602. The products are formed in 87-95% yield, with high optical purity (96-99% ee). Since this y-lactam is very important, as an intermediate and target in the synthesis of natural products, this simple reaction is a very useful addition to the synthetic chemist s arsenal. Most other preparations of this target usually lead to racemic mixtures603-606. 

The Shibasaki cychzation of mc.vo-cyclohexa-1,4-dienes in the presence of a chiral palladium complex and silver carbonate in l-methyl-2-pyrrolidinone is probably the first example of an enantioselective Heck reaction (Scheme 10.34).60 The enantiomeric excess could be slightly improved by replacing the chiral phosphine ligand BINAP with the corresponding less coordinating arsine ligand, as well as replacing silver carbonate with silver phosphate.61,62... 

Chiral bicyclic lactams are excellent precursors to a wide variety of chiral, non-racemic carbocycles including cyclopentenones, cyclohexenones, cyclopropanes, indanones, naphthalenones, and asymmetric keto acids.3 Recently they have been applied to the synthesis of chiral, non-racemic pyrrolidines and pyrroiidinones,4 that are medicinally and synthetically important molecules.5 The three-step procedure described here provides an efficient route (overall yield 46%) to (S)-5-heptyl-2-pyrrolidinone of high enantiomeric purity. The scheme below illustrates this reaction. 

Shibasaki and co-workers used (R)-BINAP as a chiral ligand for the enantioselective Heck cyclization of prochiral vinyl iodide 5.11 to cz5-decalin 5.12. Silver carbonate was used as a base and N-methyl-2-pyrrolidinone (NMP) as a solvent. 

Enantiomerically pure 2-azetidinones are applied to the asymmetric synthesis of nonracemic 2-piperidones. This is a novel application of 2-azetidinones <03T6445>. Because 2-azetidinones are valued as antibacterials and chiral building blocks for amino acids, peptides and 2-pyrrolidinones, they are readily accessible for application to this transformation. 

Optically active adducts were obtained in the presence of catalytic amounts of a chiral Lewis acid. For example, the reaction of A -benzylhydroxylamine and pyrrolidinone cinnamate 565 catalysed by Mg(C104)2 in the presence of the bisoxazoline ligand 503 gave the isoxazolidinone 566 in 80% yield and 96% ee (Scheme 137) <20000L3393>. 

A new convenient procedure for the chiral alkylation of 5-acetoxy-2-pyrrolidinone (91) and 6-acetoxy-2-piperidinone (92) has been developed. This procedure should be useful for an extremely short chiral synthesis of the bicyclic alkaloids involving pyrrolizidine, indolizidine, and quinolizidine skeletons (88JA289). 

Thus, highly diastereoselective alkylation with the chiral tin(II) enolates 90 can readily proceed regardless of the ring size of the cyclic acylimines prepared in situ. The stereochemical outcome can be rationalized by a unified six-membered transition state 99. This can be supported by the experimental fact that the same chiral alkylation of lVl-methyl-5-acetoxy-2-pyrrolidinone with tin(II) enolate of 3-acetyl-(4S)-isopropyl-l,3-thiazolidine-2-thione (40b) gave a diastereomeric mixture of 5-alkylated products in 1 1 ratio. 

Davies, S. G., Doisneau, G. J. M., Prodger, J. C., Sanganee, H. J. Synthesis of 5-substituted-3,3-dimethyl-2-pyrrolidinones quat chiral auxiliaries. Tetrahedron Lett. 1994, 35, 2369-2372. 

Amides bearing chirality at the a-position are available from the chiral pyrrolidinone 13 through iV-acylation, alkylation, and aminolysis. Pseudoephedrine has been developed into a practical chiral auxiliary for the synthesis of a-branched carboxylic acids (and other... 

The first example of the AHR was reported in 1989, and involved the conversion of the pro chiral vinyl iodides 12a-c into the chiral decalin systems 13a-c, as shown in Scheme 3 [24]. The reaction conditions (dipolar aprotic solvent and presence of silver salts), while similar to those of a previously reported non-enantioselec-tive method [16], differ crucially in respect of the choice of chiral ligand and of solvent - very low or negligible ee s were obtained using THE, MeCN, or DMSO, with the preferred solvent being N-methyl-2-pyrrolidinone (NMP). Similarly, the widely used chiral phosphine ligands BPPM [ 1 -tert-butoxycarbonyl-4-diphe-... 

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