Asymmetric synthesis of 2-substituted cyclic amines

Cyanomethylenetributylphosphorane-mediated ring closure for the asymmetric synthesis of 2-substituted cyclic amines such as azetidines, pyrrolidines and a piperidine is reported. The desired stereochemistry at the 2-position was fixed using (S)-tert-butyl sulfinamide as a chiral auxiliary.     

Asymmetric hydrogenation for the synthesis of 2-substituted chiral morpholines

Asymmetric hydrogenation of unsaturated morpholines has been developed by using a bisphosphine-rhodium catalyst bearing a large bite angle. With this approach, a variety of 2-substituted chiral morpholines could be obtained in quantitative yields and with excellent enantioselectivities (up to 99% ee). The hydrogenated products could be transformed into key intermediates for bioactive compounds.

2-Substituted chiral morpholines were synthesized via a newly developed asymmetric hydrogenation of dehydromorpholines catalyzed by a bisphosphine–rhodium complex bearing a large bite angle.     

Asymmetric synthesis of cis-2-substituted cyclohexanamines with high optical purity

Asymmetric reductive amination of racemic 2-substituted cyclohexanones (R= methyl, ethyl, phenyl, benzyl) using optically active 1-phenyl-ethylamines yields optically active cis-cyclohexanamines.     

Asymmetric synthesis of 1,2-disubstituted cycloalkanecarboxaldehydes. procedures for the highly stereoselective preparation of cis- and trans-isomer

Procedures for the asymmetric synthesis of 1,2-disubstituted cycloalkanecarboxaldehydes ($\text{7}$) having assymetric tertiary and quaternary carbon atoms in vicinal positions from the corresponding cycloalkenecarboxaldehydes ($\text{2}$) in high diastereomeric and enantiomeric purities are described.     

Diastereoselective and enantioselective synthesis of 1,2-disubstituted cycloalkanecarboxaldehydes

A highly useful method for diastereoselective and enantioselective synthesis of trans- and cis-1,2-disubstituted cycloalkanecarboxaldehydes (trans- and cis-10), useful chiral synthons having asymmetric tertiary and quaternary carbon atoms in vicinal positions in their rings, is devised starting from cycloalkenecarboxal-dehydes (5) t-Leucine t-butyl ester (2, R=Bu^t), a highly effective chiral auxiliary reagent in the present method, can be recovered for recycling without any loss of optical purity Some mechanistic explanations on the stereochemical courses of the reactions are presented     

Asymmetric synthesis of 2-substituted butane-1,4-diols by hydrogenation of homochiral fumaramide derivatives

Diastereoselective hydrogenation of homochiral fumaramides 1 derived from (2R)-Oppolzer’s sultam was observed by analysis of the ¹H NMR spectra of the succinamide mixtures with de’s of 77–88%. Reduction of these succinamides using LiAlH₄ gave the corresponding (2S)-butane-1,4-diols and established that addition of hydrogen takes place selectively on the re-face of fumaramides 1. The stereoselectivity was confirmed by estimating the ee’s from the ¹⁹F NMR spectra of the Mosher’s diesters of the diols. This methodology was applied to the synthesis of selected pyrrolidine natural products in homochiral form.     

Asymmetric synthesis of 5-substituted pyrrolidinones via a chiral N-acyliminium equivalent

5-Substituted pyrrolidinones 5 were synthesized in good yields and with fair to good diastereoselectivities from the chiral non-racemic oxazolopyrrolidinone 4. Various nucleophiles including cuprates, silanes and phosphites were used. The chiral induction is thought to arise from a chelated N-acyliminium species.     

New synthesis of 2-substituted resorcinols

By aromatization of 2-methyl-, 2-benzyl- and 2-acetyl-2-chloro-1,3-cyclohexanedione in dimethylforamide-hydrogen chloride 25%, respectively 2-methyl-, 2-benzyl and 2-acetylresorcinol were obtained in high yields.     

Bismuth-catalyzed synthesis of 2-substituted quinazolinones

The bismuth-catalyzed oxidative condensation of aldehydes with 2-aminobenzamide under aerobic conditions is reported using ethanol as the solvent. Good to excellent isolated yields (68–95%) of the corresponding 2-substituted quinazolinones were obtained under mild reaction conditions with excellent functional group tolerance. The quinazolinones were further functionalized to afford N-allylated quinazolinones, 2-aminopyridine derivatives, and annulated polyheterocyclic compounds via transition-metal catalyzed reactions.     

Enantioselective synthesis of 2-substituted cyclobutanones

[formula: see text] An enantioselective synthesis of 2-substituted cyclobutanones has been achieved by sequential application of the titanium-mediated cyclopropanation of alpha-hydroxy esters and the pinacol-type rearrangement of the resulting alpha-hydroxycyclopropylcarbinols.     

Photochemical synthesis of 2-substituted benzothiazoles

The photochemical reaction of 1 -indolethiocarbanilides 1 , di- and tri-substituted thioureas 3–5 and 4,4 -di-methyl-2,6-dioxothiocyclohexanecarboxanilides 9 affording the respective benzothiazoles are described.     

Asymmetric synthesis of 3-substituted isoindolinones: application to the total synthesis of (+)-lennoxamine

An anionic chiral auxiliary mediated asymmetric alkylation of carbamate 2 provides 3-substituted isoindolinones 4 in high ee. This methodology was used in the first asymmetric synthesis of (+)-lennoxamine.     

Facile synthesis of 2-substituted cyclopentenones

An efficient synthesis of 2-substituted cyclopentenones is reported. Key reactions are the cylopropanation of 2,2-dimethyl-3(2H)-furanone and subsequent conversion to the title compounds by oxidative fragmentation.     

Asymmetric synthesis of β-substituted Baylis-Hillman products via lithium amide conjugate addition

A three-step protocol for the asymmetric synthesis of a range of β-substituted Baylis-Hillman products has been developed. This procedure involves the diastereoselective conjugate addition of lithium (R)-N-methyl-N-(α-methylbenzyl)amide to an α,β-unsaturated ester to generate an N-protected β-amino ester in high de. Subsequent asymmetric aldol reaction via deprotonation with LDA, transmetallation with B(OMe)₃ and addition of an aldehyde gives a range of syn-aldol products in moderate to high de. Purification of the syn-aldol products to homogeneity followed by tandem N-oxidation and Cope elimination gives the desired β-substituted Baylis-Hillman products in good yield and high de and ee.     

Asymmetric synthesis of 4-substituted prolines as conformationally constrained amino acid analogues

Treatment of readily available chiral building block 1 with (2R)-2,3-O-isopropylideneglyceraldehyde (5) provides a new route for asymmetric synthesis of 2,4-disubstituted pyrrolidines. Several proline-amino acid chimeras: proline-leucine, proline-lysine, proline-arginine and proline-glutamic acid, are synthesized in highly diastereomerically pure forms.     

Asymmetric synthesis of cis-5-substituted pyrrolidine 2-phosphonates using metal carbenoid NH insertion and delta-amino beta-ketophosphonates

Cis-5-substituted pyrrolidine phosphonates, proline surrogates, are prepared by a highly stereoselective intramolecular metal carbenoid N-H insertion from a sulfinimine-derived delta-amino alpha-diazo beta-ketophosphonate. [reaction: see text]     

RETRACTED: Asymmetric synthesis of highly enantioenriched 2-substituted piperidines and 6-substituted piperidine-2-ones by a combination enantioselective hydrazone allylation with ring closing metathesis

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy).This article has been retracted at the request of the corresponding author. The corresponding author prepared a series of cinchonine derivatives and found that the structure of PCA, which was a major compound, was mistakenly assigned. The synthetic routes, physical and spectroscopic data for the products are valid. As a result the corresponding author withdraws this publication.     

Asymmetric synthesis of a 3,4-substituted pyrrolidine by l-proline catalyzed direct enolexo aldolization

The asymmetric synthesis of a 3,4-substituted N-tosyl pyrrolidine has been achieved by using l-proline catalyzed 5-enolexo aldolization with high enantio and diastereoselectivity.