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Synthesis and Conformational Studies of Regio‐ and Conformational Isomers Derived from O ‐Benzylation of Tetrahydroxy[3.1.3.1]metacyclophanes
Author(s) -
Yamato Takehiko,
Saruwatari Yoshiyuki,
Yasumatsu Masashi,
Ide Seiji
Publication year - 1998
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/(sici)1099-0690(199802)1998:2<309::aid-ejoc309>3.0.co;2-6
Subject(s) - chemistry , regioselectivity , bromide , benzyl bromide , conformational isomerism , tetra , yield (engineering) , medicinal chemistry , structural isomer , cyclophane , stereochemistry , organic chemistry , crystal structure , catalysis , molecule , materials science , metallurgy
Regioselective O ‐benzylations of [3.1.3.1]metacyclophanes with intraannular OH groups are described. O ‐Benzylation of 6,13,22,29‐tetra‐ tert ‐butyl‐9,16,25,32‐tetrahydroxyy[3.1.3.1]metacyclophane 1 with 2 equiv. of benzyl bromide in the presence of Na 2 CO 3 leads to exclusive formation of the monosubstituted product 3 . In contrast, use of K 2 CO 3 as the base leads to di‐ O ‐substitution, resulting in the disubstituted product, distal ‐ 4 , as the major product, along with some 1,2‐ proximal ‐ 4 , in spite of using a large excess of benzyl bromide. Under the same reaction conditions in the presence of Cs 2 CO 3 , a mixture of two conformers of the tetra‐ O ‐benzylated product 2 in a ratio of 80:20 ( cone ‐ 2 ‐1,4‐ alternate ‐ 2 ) is obtained in 83% yield. Thus, the alkali metal cation plays not only an important role with regard to the regioselectivity, but also in determining the number of O ‐benzylations that occur, as a consequence of the template effect. Regioselective syntheses of dimethoxy‐ and trimethoxy[3.1.3.1]metacyclophanes are accomplished by a protection‐deprotection strategy, using the benzyl residues as protecting groups. The 1 H‐NMR spectra of these macrocyclic metacyclophanes are also discussed.