Organocatalyzed Michael–Michael Cascade Reaction: Asymmetric Synthesis of Polysubstituted Chromans

Abstract

An enantioselective cascade Michael-Michael reaction between chalcones enolates and nitromethane catalyzed by a bifunctional thiourea is developed. This reaction provides a mild but efficient approach to chiral benzopyrans bearing three consecutive stereocenters in high yields with excellent stereoselectivities, and the benzopyrans can be easily transformed to the corresponding tricyclic product.

Recent Progress in Organocatalytic Asymmetric Domino Transformations

“…[185] Luo,X u, and co-workers utilized ortho-disubstituted enolates 486 andn itromethane (487)a st he substrates in an asymmetric domino double Michaelreaction catalyzed by ah ydroquinine-derived thiourea catalyst 489.A ss hown in Scheme 125,t he corresponding chroman derivatives 488 were obtained in high yieldsand stereoselectivities. [186] An asymmetric domino sulfa-Michael/Michael addition involving thiosalicylates 490 andn itroalkene enoates 491 catalyzed by squaramide 494 was realized by Du and co-workers for the synthesis of chiral chromans (Scheme 126). [187] Thea uthors also isolated the intermediate thia-Michael addition product 492 and further transformedi tt o493 under the optimized reaction conditions.S ince both anti-492 and syn-492 producedt he same stereoisomer of 493,t he authors proposedasulfa-Michael/retro-sulfa-Michael/sulfaMichael/Michael reactionp rocess that involved ad ynamic kinetic resolution to explain the experimental results (Scheme 126).…”

“…[186] As shown in Scheme 150, ortho-functionalized aromatic dienones 577 was reacted with nitromethane (487) under the catalysis of the hydroquinidine-derived thiourea catalyst 579 to produce the indane derivatives 578 in good to high yields and stereoselectivities. [222] Thee nantiomers of 578 could be simply obtainedi n similars tereoselectivities by using the hydroquininederivedc atalyst 489 (a pseudo-enantiomer of 579).…”

One-Pot Multicomponent Synthesis of Highly Functionalised Piperidines from Aromatic Aldehydes, Cyanoacetates, Nitromethane and Ammonium Acetate

“…Subsequently, the residues were added with water (15 mL) and were extracted with dichloromethane (3 × 15 mL), the organic phase was washed with water and brine, dried over anhydrous sodium sulfate. The crude products were purified by flash chromatography (silica gel, EtOAc/hexanes, 1 / 2) to give products 2a-i and 3a-g. 4, 8, 159.6, 159.5, 129.7, 128.8, 128.7, 124.3, 115.6, 114.2, 114.0, 113.6, 90.6, 65.4, 64.5, 62.6, 60.5, 55.1, 50.8, 13.6;IR (KBr, cm -1 ): 3191, 3078, 2948, 2838, 2256, 1695, 1613, 1551, 1574, 1454, 1421, 1343, 1256 H,5.73;N,7.70. Found: C,66.22;H,5.60;N,4, 4, 161.7, 159.4, 159.2, 158.9, 154.9, 136.0, 133.8, 132.5, 130.0, 129.7, 129.3, 123.0, 119.9, 119.7, 115.0, 114.1, 113.9, 113.7, 102.6, 89.9, 65.8, 64.7, 62.3, 59.3, 55.2, 55.1, 55.0, 51.2, 13.3;IR (KBr, cm -1 ): 3019, 2953, 2854, 2216, 1728, 1643, 1608, 1382, 1273 ,5.73;N,7.70.…”

“…The crude products were purified by flash chromatography (silica gel, EtOAc/hexanes, 1 / 2) to give products 2a-i and 3a-g. 4, 8, 159.6, 159.5, 129.7, 128.8, 128.7, 124.3, 115.6, 114.2, 114.0, 113.6, 90.6, 65.4, 64.5, 62.6, 60.5, 55.1, 50.8, 13.6;IR (KBr, cm -1 ): 3191, 3078, 2948, 2838, 2256, 1695, 1613, 1551, 1574, 1454, 1421, 1343, 1256 H,5.73;N,7.70. Found: C,66.22;H,5.60;N,4, 4, 161.7, 159.4, 159.2, 158.9, 154.9, 136.0, 133.8, 132.5, 130.0, 129.7, 129.3, 123.0, 119.9, 119.7, 115.0, 114.1, 113.9, 113.7, 102.6, 89.9, 65.8, 64.7, 62.3, 59.3, 55.2, 55.1, 55.0, 51.2, 13.3;IR (KBr, cm -1 ): 3019, 2953, 2854, 2216, 1728, 1643, 1608, 1382, 1273 ,5.73;N,7.70. Found: C,66.24;H,5.62;N,4, 164.70, 154.93, 144.41, 138.6, 138.2, 134.7, 130.0(2C), 129.9(2C), 129.4(2C), 129.2(2C), 128.8(2C), 127.4(2C), 115.…”

“…Found: C,66.22;H,5.60;N,4, 4, 161.7, 159.4, 159.2, 158.9, 154.9, 136.0, 133.8, 132.5, 130.0, 129.7, 129.3, 123.0, 119.9, 119.7, 115.0, 114.1, 113.9, 113.7, 102.6, 89.9, 65.8, 64.7, 62.3, 59.3, 55.2, 55.1, 55.0, 51.2, 13.3;IR (KBr, cm -1 ): 3019, 2953, 2854, 2216, 1728, 1643, 1608, 1382, 1273 ,5.73;N,7.70. Found: C,66.24;H,5.62;N,4, 164.70, 154.93, 144.41, 138.6, 138.2, 134.7, 130.0(2C), 129.9(2C), 129.4(2C), 129.2(2C), 128.8(2C), 127.4(2C), 115. 8,101.1,90.5,65.6,64.8,62.8,62.2,51.0,21.3,20.6,20.5,13.5;IR (KBr, …”