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A Study on the Allylic Substitution of (1 R ,5 R ,8 R )‐ and (1 R ,5 R ,8 S )‐8‐Hydroxy‐2‐oxabicyclo[3.3.0]oct‐6‐en‐3‐one Derivatives − Preparation of (1 S ,2 R ,3 R )‐9‐[2‐Hydroxy‐3‐(2‐hydroxyethyl)cyclopent‐4‐en‐1‐yl]‐9 H ‐adenine
Author(s) -
Johansen Steen K.,
Lundt Inge
Publication year - 2001
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 - 10.1002/1099-0690(200103)2001:6<1129::aid-ejoc1129>3.0.co;2-t
Subject(s) - chemistry , nucleophile , nucleophilic substitution , allylic rearrangement , mitsunobu reaction , moiety , stereochemistry , bicyclic molecule , substitution reaction , nucleoside , dimethyl malonate , medicinal chemistry , organic chemistry , palladium , catalysis
The palladium‐catalyzed substitution of acylated (1 R ,5 R ,8 R )‐ and (1 R ,5 R ,8 S )‐8‐hydroxy‐2‐oxabicyclo[3.3.0]oct‐6‐en‐3‐ones has been studied using a number of C‐ and N‐nucleophiles. In all cases, the exo derivatives (8 R ) were found to be more reactive than the corresponding endo derivatives (8 S ). The reaction was found to give good yields and a single product when sodium dimethyl malonate was used as the nucleophile. However, when less reactive C‐ and N‐nucleophiles were employed, the reaction gave inseparable mixtures of both C‐6 and C‐8 substituted products, thus limiting the synthetic use of the reaction with these nucleophiles. Additionally, Mitsunobu substitution of (1 R ,5 R ,8 R )‐8‐hydroxy‐2‐oxabicyclo[3.3.0]oct‐6‐en‐3‐one ( 3 ) with 6‐chloropurine, followed by reduction of the lactone moiety and treatment with liquid ammonia, gave the carbocyclic nucleoside (1 S ,2 R ,3 R )‐9‐[2‐hydroxy‐3‐(2‐hydroxyethyl)cyclopent‐4‐en‐1‐yl]‐9 H ‐adenine ( 19 ), which can be viewed as an analogue of the carbocyclic nucleoside BCA.