Palladium(0)-catalyzed coupling-cyclization reaction of polymer-supported aryl iodides with 1,2-allenyl carboxylic acids. Solid-phase parallel synthesis of butenolides.
In this contribution, we constructed a library of butenolides with 77 members by parallel synthesis strategy on Merrifield resin. Sixteen 2,3-allenoic acids and 12 polymer-bound aryl iodides were combined to react with each other, and then the polymer-supported products were cleaved to release butenolide derivatives. The reactions with alkyl-substituted 2,3-allenoic acids in acetonitrile afforded the corresponding products in high yields and high purities, whereas those with aryl-substituted acids in acetonitrile failed. After some reaction conditions were screened, the solid-phase reactions with aryl-substituted 2,3-allenoic acids were realized in toluene, and the products are of good purities albeit in slightly low yields. In the benzyl ether linkage, a new cleavage model was found. By adding 6 equiv of acetyl bromide, we can get single (5-oxo-2,5-dihydrofuran-3-yl)benzyl bromide other than the corresponding benzyl acetate. To further increase the diversities, a dihydropyran (DHP) linker was introduced into our combinatorial synthesis of butenolides. By reversing the addition sequence of 2,3-allenoic acids and organic base, we realized the solid-phase cyclization reaction of polymer-bound aryl iodides with the THP linkage in moderate yields and good purities. Now the library of butenolides includes (5-oxo-2,5-dihydrofuran-3-yl)benzoic acids, -aryl acetates, -benzyl bromides, -benzyl alcohols, and -phenols, which are difficult to synthesize with conventional solution methods.
Ma
Shengming
S
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, P. R. China.
Duan
Dehui
D
Wang
Yizhong
Y
D015107:4-Butyrolactone / Q000031:analogs & derivatives; D002264:Carboxylic Acids / Q000737:chemistry; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D003432:Cross-Linking Reagents / Q000737:chemistry; D003500:Cyclization; D004987:Ethers / Q000737:chemistry; D005663:Furans / Q000138:chemical synthesis*; D006847:Hydrocarbons, Iodinated / Q000737:chemistry; D010165:Palladium / Q000737:chemistry; D012117:Resins, Synthetic / Q000737:chemistry
D002264:Carboxylic Acids; D003432:Cross-Linking Reagents; D004987:Ethers; D005663:Furans; D006847:Hydrocarbons, Iodinated; D012117:Resins, Synthetic; D010165:Palladium; C004511:butenolide; D015107:4-Butyrolactone