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Synthesis of Substituted 1‐Alkylidenephthalanes via Lithium‐Promoted 5‐ exo ‐ dig Cyclization
Author(s) -
Bunse Paul,
Würthwein ErnstUlrich,
Wünsch Bernhard
Publication year - 2018
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201800205
Subject(s) - chemistry , regioselectivity , moiety , medicinal chemistry , methylene , orthoester , propyne , nucleophile , lithium (medication) , butyllithium , stereochemistry , organic chemistry , catalysis , medicine , endocrinology
A one‐pot synthesis of 1‐alkylidenephthalanes from 3‐(2‐bromophenyl)propyne derivatives has been developed. 3‐(2‐Bromophenyl)propynal acetals 9 and corresponding orthoester 19 were treated successively with n ‐butyllithium and various aldehydes and ketones at low temperature to obtain 1‐alkylidenephthalanes 10 and 20 with various functional groups at the exocyclic methylene moiety. Halogen‐metal exchange, nucleophilic addition to various carbonyl compounds, regioselective 5‐ exo ‐dig cyclization of the respective intermediate lithium alcoholate and hydrolysis represent the key steps in this Domino reaction. A two‐step mechanism involving at first a synchronous cyclization to form a vinyllithium intermediate and then a methoxide elimination leading to the respective 1‐methoxy allenes is suggested based on DFT‐calculations.