Oxa‐Michael–Michael Reaction of MBH Alcohol and 2‐Arylidene‐1,3‐indanedione: Regioselective Formal [4+2] Cycloaddition towards Tetrahydrospiropyran Scaffolds

• Published in: European journal of organic chemistry Vol. 2019; no. 12; pp. 2234 - 2242
• Main Authors: Gudise, Veera Babu, Settipalli, Poorna Chandrasekhar, Reddy, Eeda Koti, Anwar, Shaik
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 31.03.2019; Wiley Subscription Services, Inc
• Subjects: Alcohol; Ambiphilicity; Aromatic compounds; Cesium; Chemical bonds; Chemistry; Chemistry, Organic; Cycloaddition; C–C coupling; Derivatives; Michael reaction; Nucleophilic addition; Organic chemistry; Physical Sciences; Regioselectivity; Science & Technology; Spiro compounds; Substrates; C-C coupling; ANNULATION STRATEGY; ASYMMETRIC-SYNTHESIS; CASCADE REACTIONS; ENANTIOSELECTIVE SYNTHESIS; Ambiphilicity; BAYLIS-HILLMAN REACTION; 2-ARYLIDENEINDANE-1,3-DIONES; Cycloaddition; DIASTEREOSELECTIVE SYNTHESIS; STEREOSELECTIVE-SYNTHESIS; DERIVATIVES; Spiro compounds; NITROALKENES; Nucleophilic addition
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201801709

A regioselective formal [4+2] cycloaddition reaction of nitrostyrene derived MBH alcohol and 2‐arylidene‐1,3‐indanedione resulted in functionalized tetrahydrospiropyran derivatives with excellent chemical yields (up to 93 %). The reaction tolerated various electron rich and electron deficient substituents on the aryl group of 2‐arylidene‐1,3‐indanedione as well as MBH alcohol. The utility of MBH alcohol as an ambident substrate, which is performing the dual role of nucleophile and electrophile with 2‐arylidene‐1,3‐indanediones was successfully demonstrated for 20 derivatives. A single isomer was obtained exclusively in all the products via cascade process which followed an oxa‐Michael–Michael addition sequence using cesium carbonate as base. Control experiments were carried out to understand the mechanistic details of the reaction. These experiments prove that the reaction undergoes a stepwise pathway rather than a concerted mechanism. Functionalized tetrahydrospiropyran derivatives can be easily accessed regioselectively by the use of nitrostyrene derived MBH alcohols and 2‐arylidene‐1,3‐indanediones in high chemical yields (up to 93 % yield). The synthetic utility of MBH alcohol as an ambiphilic substrate towards the synthesis of spirocyclic skeletons is noteworthy.