Selective Acetalization in Pyridine: A Sustainable 5'-O-(2-Methoxypropyl) Protecting Group in the Synthesis of
Verneri Saari1, Aino Eerola1, Mikko Ora1
1Department of Chemistry, University of Turku, 20500 Turku, Finland.
Abstract:
A mixture of 2-methoxypropene and an acid catalyst in pyridine results in an efficient 5'-O-(methoxyisopropyl) (MIP) acetalization of nucleosides, including 2'-deoxy, 2'-OH, 2'-O-methyl, 2'-O-methoxyethyl (MOE) and 2'-F-variants, in 44-77% isolated yields. For the reaction mechanism, we propose a pyridinium 2-methoxyprop-2-yl preassociation complex, which improves regioselectivity for the primary (5'-OH) over secondary (2'-OH and 3'-OH) hydroxy groups. The developed protocol makes the 5'-O-MIP-acetal an attractive protecting group for the sustainable synthesis of nucleosides and oligonucleotides in solution.
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