Cyclopenta[b]thiophene-alkyloxazolines: new nitrogen–sulfur hybrid ligands and their use in asymmetric palladium-catalyzed allylic alkylation
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Introduction
The search for new ligands in asymmetric catalysis is a field of continuing interest. To facilitate practical applications, new ligands should be easy to prepare from simple and easily accessible starting materials. In this context the use of nitrogen and sulfur containing ligands is growing. Recent reports have shown that these compounds are suitable for many types of catalysis.1 Among chiral moieties containing nitrogen, oxazolines have several advantages as sources of chirality, the principal being that they are readily accessible from homochiral amino alcohols and have proven to be effective catalysts in a variety of reactions.2 The use of a second different heteroatom binding site to induce electronic bias in the intermediate catalyst–substrate complex has been reported so far, often with sulfur being used for this purpose. Whereas the thioeter moiety has been frequently used,3 thiophene has only occasionally been employed,4 although there are reports of thiophene functioning as either η1 or η5 ligands.5 High stability and fairly good accessibility from the chiral pool, highlight some beneficial aspects of ligands based on sulfur and nitrogen when compared with phosphines. Furthermore the thiophene–oxazoline combination in ligands for asymmetric catalysis has for the most part been largely overlooked.6
Herein we report the synthesis of novel bidentate ligands (Fig. 1) with two stereogenic centres with an oxazoline moiety linked to a rigid cyclopenta[b]thiophene,5,6,-dihydro backbone in which the sulfur atom is part of a strong π-donor structure.
The first promising results with these chiral ligands for the enantioselective palladium-catalyzed allylic substitution are also described.
Section snippets
Synthesis of the ligands
The different cyclopenta[b]thiophene-alkyloxazolines (CPTOx’s) have been synthesized following classical synthetic procedures for oxazolines. The 5-methyl-4,5-dihydro-4H-cyclopenta[b]thiophen-6-one was prepared using the one-pot reaction developed by Meth-Cohn and Gronowitz.7 Under treatment of this ketone with MeI and KOH in the presence of catalytic amounts of 18-crown-ether the 5,5 dimethyl derivative 1 was isolated in 91% yield. For the synthesis of racemic carboxylic acid rac-4, 1 was
Conclusions
We have prepared four new bidentate S–N ligands with multiple stereogenic elements and with (S)-oxazoline and (6R)- or (6S)-cyclopenta[b]thiophene moieties as homochiral cores. The ligands, available in five simple synthetic steps in good yields and fairly large amounts, were stable and reusable. They were tested in Pd-catalyzed asymmetric allylic alkylation, reaching in all cases almost quantitative yields of the alkylation product and up to 74% ee. With these ligands the observation that the
Experimental
Melting points (uncorrected) were determined with a Büchi melting point apparatus. 1H NMR and 13C NMR spectra were recorded using CDCl3 solutions at 300, 400 and 600 MHz for 1H and 75.46, 100.6 and 150.92 MHz for 13C. Chemical shifts (δ) are reported in ppm relative to CHCl3 (δ=7.26 for 1H and δ=77.0 for 13C or 7.24 and 128.0 ppm for C6D6). J values are given in Hz. 1H NMR and 13C NMR spectral assignments were made by DEPT, gCOSY and gHSQC experiments. IR spectra were recorded on a Perkin–Elmer
Acknowledgements
We acknowledge financial support by the National Project ‘Stereoselezione in Sintesi Organica. Metodologie ed Applicazioni’ 2002–2003 and by the RTN project ‘Design, Analysis and Computation for Catalytic Organic Reactions’ (contract HPRN-CT-2001-00172).
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Cited by (13)
Chiral sulfur-containing ligands for asymmetric catalysis
2007, TetrahedronCitation Excerpt :This latter process has attracted considerable attention, because of the mild reaction conditions and the high functional-group tolerance that the zinc reagents offer.108 The enantioselective version of the 1,4-addition of Grignard reagents to α,β-unsaturated carbonyl compounds has been less studied in recent years, but extensively developed in the past, using different mono- and bidentate chiral ligands such as monodentate thiosugars,109 heterobidentate S,N-ligands,110 oxazoline arenethiolates,111 S,O-ligands112 and S,P-ligands.113 Other chiral N,S-donor ligands, derived from l-proline and (S)-phenylglycine, have been used in the copper-catalysed conjugate addition of MeLi to enones.114
Chapter 5.1 Five-membered ring systems: thiophenes and Se/Te analogues
2005, Progress in Heterocyclic ChemistryCitation Excerpt :Thienyl end-capped 2,5-(arylethynyl)thiophenes have been included in a study on the fluorescent properties of a group of related structures <04TL7061>. In addition, new fluorescent 2-(2’,2’-bithienyl)-1,3-benzothiazoles have been synthesized and evaluated <04TL2825>. Further advances in the field of thiophene containing compounds for potential use in electronic or optical devices include synthesis of 117 together with a related system and their oriented assembly between two gold electrodes for control of electron transport <04AG(E)4471>, and synthesis and studies of the new chromophore 118, which displayed large molecular hyperpolarizability, useful for photonic switching at frequencies over 100 GHz <04JOC8239>.
Chapter 5.7 Five-membered ring systems: with O & N atoms
2005, Progress in Heterocyclic ChemistryCitation Excerpt :Novel C2 symmetric chiral bis(oxazoline) ligands have been also synthesized. Derivatives 150, bearing a dibenzo[a,c]cycloheptadiene skeleton and a hydroxyalkyl group on the oxazoline rings, were applied in the catalytic asymmetric addition of diethylzinc to aromatic aldehydes (up to 96% ee) <04TA119>, while new xanthene (XaBOX) ligands 151 were evaluated in 1,3-DC reactions of nitrones with 3-crotonoyl-2-oxazolidinone in the presence of Mn(II) or Mg(II) perchlorate (92-98% de; 91-98% ee for the endo adduct) <04TL2121>. A new class of substituted o-alkoxyaryl bis(oxazoline) ligands 152 have been introduced providing the highest enantioselectivities (up to 98% ee) yet reported for copper(II)-catalyzed asymmetric dienolsilane aldol addition to pyruvate and glyoxylate esters <04OL4097>.