Regioselective ring openings in the 3,5-dioxa-8-azabicyclo[5.2.0]nonane ring system

Zsuzsanna Sánta,Pál Kolonits,József Nagy,József Nyitrai,Ramaiah Muthyala

doi:10.3998/ark.5550190.0009.302

Abstract

In order to distinguish primary and secondary hydroxyl groups in the presence of a β-lactam moiety benzylidene acetal protection and reductive cleavage were used. When the reductive ring opening was carried out using diisobutylaluminium hydride, the benzylidene acetal group remained intact, while the β-lactam was reduced to the corresponding β-amino alcohol. The acetal cleavage with sodium cyanoborohydride was successful, resulting mainly in a β-lactam compound bearing the benzyloxy group on the secondary carbon atom.

Highlights

In the course of our work in the synthesis of 2-iso-oxacephems, we faced the problem of distinguishing between primary and secondary hydroxyl groups with an appropriate protecting group strategy.[1]
We needed a compound having a protecting group (G), which is stable to acids and mild bases, on the secondary O, but contains a free primary hydroxyl group, which can be mesylated to give 2 (Scheme 1, PMP = p-methoxyphenyl)
This compound bears the acetoxy group on the primary carbon atom, presumably due to a transacetylation reaction occurring because of the spatial proximity of the two hydroxyl groups (Scheme 2).[1]

Summary

Introduction

In the course of our work in the synthesis of 2-iso-oxacephems, we faced the problem of distinguishing between primary and secondary hydroxyl groups with an appropriate protecting group strategy.[1]. It is reported that its regioselective reductive cleavage can be accomplished with DIBALH or alane (LAH/AlCl3) to give the free hydroxyl group in the less hindered position and the benzyl ether moiety in the more hindered position (Scheme 3).[2] The reaction was carried out at -78 °C, resulting in the same main compound with a much better yield and fewer minor products.

Results

Conclusion