Evidence for Atropisomerism in Polycyclic γ-Butenolides: Synthesis,Scope, and Spectroscopic Studies

Design and development of a domino cyclative approach for the synthesis of new polycyclic γ-butenolides from β-aryl-Z-enoate propargylic alcohols, through the interception of an intermediate of the Z-enoate-assisted Meyer–Schuster rearrangement, has been reported. A systematic NMR analysis of various derivatives of this class revealed and supported the potential atropisomerism associated with them. These molecules represent first examples of butenolide ring-based atropisomeric compounds in organic chemistry. The synthetic process involves a synchronous construction of both rings with concurrent creation of the potential stereogenic rotational axis.     

Catalytic,Asymmetric Synthesis of Phosphonic γ‐(Hydroxyalkyl)butenolides with Contiguous Quaternary and Tertiary Stereogenic Centers

A procedure that enables high yielding access to phosphonic γ‐(hydroxyalkyl)butenolides with excellent regio‐, diastereo‐ and enantiocontrol is reported. The simultaneous construction of up to two adjacent quaternary stereogenic centers by a catalytic asymmetric vinylogous Mukaiyama aldol reaction unites biologically and medicinally relevant entities, namely α‐hydroxy phosphonates and γ‐(hydroxyalkyl)butenolides. This is achieved by utilizing a readily available chiral copper‐sulfoximine catalyst showing a broad functional group tolerance for both the electrophilic and nucleophilic reactants. A discussion about potential factors affecting the observed level of enantioselectivity, which stems from the enantiopure sulfoximine ligand, is also included.     

First Synthesis of Mosquito Larvicidal Butenolides I and II

ＩｎｔｒｏｄｕｃｔｉｏｎＶｅｒｙｒｅｃｅｎｔｌｙ ,ｔｗｏｎｅｗｍｏｓｑｕｉｔｏｌａｒｖｉｃｉｄａｌｂｕｔｅｎｏ ｌｉｄｅｓＩ (1)ａｎｄＩＩ (2 )ｗｅｒｅｉｓｏｌａｔｅｄｂｙＫａｒｕｎａｒａｔｎｅｅｔａｌ.1ｆｒｏｍｔｈｅｌｅａｖｅｓｏｆａｌｌｔｈｒｅｅｓｐｅｃｉｅｓｏｆＨｏｒｔｏｎｉａ (ｆａｍ ｉｌｙＭｏｎｉｍｉａｃｅａｅ) (Ｈ .ａｎｇｕｓｔｉｆｏｌｉａ ,Ｈ .ｆｌｏｒｉｂｕｎｄａａｎｄＨ .ｏｖａｌｉｆｏｌｉａ) .Ｂｏｔｈｂｕｔｅｎｏｌｉｄｅｓｅｘｈｉｂｉｔｅｄｍｏｓｑｕｉｔｏｌａｒ ｖｉｃｉｄａｌａｃｔ…     

A facile approach to spirocyclic butenolides through cascade cyclization/oxidative cleavage reactions of (Z)-enynols catalyzed by gold under dioxygen atmosphere

A facile approach for the syntheses of spirocyclic butenolides through cascade cyclization/oxidative cleavage reactions of (Z)-enynols bearing cyclic substituents at the C-1 position catalyzed by gold under dioxygen atmosphere has been developed. A variety of substituted butenolides was constructed in a regioselective manner from suitably substituted (Z)-2-en-4-yn-1-ols. (Z)-Enynols substituted both at C2 and C3-position afforded the spirocyclic butenolides in moderate to good yields, C-2 unsubstituted (Z)-enynols afforded the products in moderate yields, and the C-3 unsubstituted (Z)-enynols afforded the desired products in low yields.     

Regio- and stereoselective preparation of γ-alkylidenebutenolides or α-pyrones using a Stille reaction and palladium-catalysed oxacyclisation sequence

Synthesis of butenolides or α-pyrones from substituted tributylstannyl acetylides is highly dependant on the nature of the acetylide.     

Stereoselective syntheses of dihydroxerulin and xerulinic acid, anti-hypocholesterolemic dyes from the fungus Xerula melanotricha

The title compounds 2 and 3, which are inhibitors of the biosynthesis of cholesterol, were synthesized in a convergent and perfectly stereoselective manner. In the key step, bromobutenolide 6 (obtained from levulinic acid in two steps) was coupled with either of the novel bis(stannanes) trans,cis,trans-35 or trans,trans,trans-35 [each accessible from 3-(tributylstannyl)allyl alcohol (17) in four steps], giving gamma-alkylidenebutenolide trans,trans,trans-32. This compound was coupled with iododiyne 42 or the bromoenediynoate 44 leading to dihydroxerulin (2) and to the (trimethylsilylethyl)ester 45 of xerulinic acid, respectively. Deprotection of the latter provided totally synthetic xerulinic acid (3) for the first time.     

Domino Reactions with Fluorinated Five-membered Heterocycles – Syntheses of Trifluoromethyl Substituted Butenolides and γ-Ketoacids

Summary. A new approach to trifluoromethyl substituted butenolides and their thioanalogues is described starting from 2-fluoro-3-trifluoromethylfurans and -thiophenes, respectively. The reaction sequence includes three steps – nucleophilic displacement reaction, Claisen, and finally Cope rearrangement – which can be run as domino reaction. A modification of the domino reaction (transesterification instead of Cope rearrangement) provides a concise access to α-trifluoromethyl-γ-ketoacids.     

Direct Enantioselective Vinylogous Mannich Reaction of Ketimines with γ‐Butenolide by Using Cinchona Alkaloid Amide/Zinc(II) Catalysts

A direct enantioselective vinylogous Mannich reaction of ketimines with γ‐butenolide has been developed. Good yields and enantioselectivities were observed for the reaction of various ketimines by using a cinchona alkaloid amide/Zn(OTf)₂ catalyst and Et₃N. Both enantiomers of the products could be obtained by using pseudoenantiomeric chiral catalysts.