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SiliCycle Inc.
2500 Parc Technologique Blvd.
Quebec City, (Quebec) G1P 4S6 Canada
1 418 874.0355
1 877 745.4292 (Toll Free North America Only)
1 418 874.0054
[email protected]
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A library of 352 complex pyran-containing macrocycles was synthesized through the use of modular fragments and rapid
solid-phase assisted parallel solution-phase techniques. A straightforward synthetic path featuring the use of Silia
Bond
reagents in a SiliCycle MiniBlock afforded the expected macrocycles in both high yield and purity.
The key steps involve an amide coupling using Silia
Bond
Carbodiimide (DCC) followed by work-up with Silia
Bond
Carbonate and
Silia
Bond
Carboxylic Acid to remove excess reagents and starting materials. An S
N
Ar reaction allowed closure of the macrocycle,
once again followed by a purification step involving Silia
Bond
Carbonate.
SiliCycle MiniBlock XT is extremely useful for complex, multi-step synthesis protocols where a variety of volumes and reaction
conditions are needed. Several steps in the synthesis described below were run at reflux and under inert conditions. Multiple
steps required different scales and a variety of reaction arrays to be used.
In this example, parallel solution-phase synthesis of a series of libraries involving the synthesis of hexahydro-1H-isoindolones
was performed exploiting a novel “tactical combination” of Cu-catalyzed three-component coupling and Diels–Alder reactions.
Three distinct libraries consisting of 24 members, 60 members, and 32 members were constructed. Additional sub libraries of
isoindolone scaffolds were prepared initially in a one-pot/two-step process and were further diversified via Pd-catalyzed Suzuki cross-coupling
reactions with boronic acids at two different diversification points.