Stereodivergent organocatalytic intramolecular michael addition/ lactonization for the asymmetric synthesis of substituted dihydrobenzofurans and tetrahydrofurans

The authors thank the Royal Society for a University Research Fellowship (A.D.S.), the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007–2013), ERC Grant Agreement No. 279850 (A.D.L.H. and J.E.T.), and the EPSRC (DTA studentship to D.B.) for funding.A stereodivergent asymmetric Lewis base catalyzed Michael addition/lactonization of enone acids into substituted dihydrobenzofuran and tetrahydrofuran derivatives is reported. Commercially available (S)-(-)-tetramisole hydrochloride gives products with high syn diastereoselectivity in excellent enantioselectivity (up to 99:1 d.r. , 99% ee), whereas using a cinchona alkaloid derived catalyst gives the corresponding anti-diastereoisomers as the major product (up to 10:90 d.r., 99% ee). You can have it both ways! A stereodivergent asymmetric Lewis base catalyzed Michael addition/lactonization of enone acids into substituted dihydrobenzofuran and tetrahydrofuran derivatives is reported, giving products with high d.r. and ee (see scheme).Publisher PDFPeer reviewe

Synthesis of di-, tri-, and tetrasubstituted pyridines from (phenylthio)carboxylic acids and 2-[aryl(tosylimino)methyl]acrylates

We thank the Royal Society (ADS), Syngenta/EPSRC (DGS), and the EPSRC National Mass Spectrometry Facility at Swansea University.An isothiourea-catalyzed Michael addition–lactamization followed by the sulfide oxidation–elimination/N- to O-sulfonyl transfer sequence for the formation of 2,3,5- and 2,3-substituted pyridine 6-tosylates from (phenylthio)acetic acids and α,β-unsaturated ketimines is described. Incorporation of the valuable 2-sulfonate group allows derivatization to a range of di-, tri-, and tetrasubstituted pyridines.PostprintPeer reviewe

Asymmetric Michael Addition-Lactonization of Carboxylic Acids

A highly efficient asymmetric intra- and intermolecular Michael addition-lactonization of a variety of enone acids, arylacetic acids, and α-keto-β,γ-unsaturated esters using chiral isothioureas as catalysts was reported. The combination of an activating agent and the catalyst was crucial to generate an efficient catalytic cycle. To further demonstrate the utility of this process, the authors performed a simple derivatization of the products to obtain indene carboxylates in good yields and high enantioselectivities

Telescoped Synthesis of Stereodefined Pyrrolidines

Telescoped and one-pot olefination/asymmetric functionalization approaches to disubstituted pyrrolidines (dr up to 99:1, up to 99% ee) have been developed using commercially available tetramisole (0.1 to 5 mol %). Using OTMS-quinidine as the Lewis base gives preferential access to an <i>anti</i>-configured pyrrolidine in high enantioselectivity

6-exo-trig Michael addition-lactonizations for catalytic enantioselective chromenone synthesis

The authors thank the EPSRC Centre for Doctoral Training in Critical Resource Catalysis (CRITICAT, grant code EP/L016419/1, RMNP) for funding.The European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013) ERC Grant Agreement No. 279850 is also acknowledged. ADS thanks the Royal Society for a Wolfson Research Merit AwardThe catalytic enantioselective 6-exo-trig Michael addition-lactonization of enone-acid substrates to form cis-chromenones with high diastereo- and enantiocontrol was developed using the commercially available isothiourea tetramisole. An acidic workup proved necessary to minimize product epimerization and maximize product er, providing cis-chromenones in excellent yield, and with excellent diastereo- and enantioselectivity.Publisher PDFPeer reviewe

Structure-enantioselectivity effects in 3,4-dihydropyrimido[2,1-b]-benzothiazole-based isothioureas as enantioselective acylation catalysts

The catalytic activity and enantioselectivity in the kinetic resolution of (+/-)-1-naphthylethanol with a range of structurally related 3,4-dihydropyrimido[2,1-b]benzothiazole-based catalysts is examined. Of the isothiourea catalysts screened, (2S,3R)-2-phenyl-3-isopropyl substitution proved optimal, giving good levels of selectivity in the kinetic resolution of a number of secondary alcohols (S values up to &gt; 100 at similar to 50% conversion). Low catalyst loadings (0.10-0.25 mol%) of the optimal isothiourea can be used to generate enantiopure alcohols (&gt;99% ee) in good yields.</p