Noncovalent solid-phase organic synthesis explained

Noncovalent solid-phase organic synthesis or NC-SPOS is a form of Solid-phase synthesis whereby the organic substrate is bonded to the solid phase not by a covalent bond but by other chemical interactions. This bond may consist of an induced dipole interaction between a hydrophobic matrix and a hydrophobic anchor. As long as the reaction medium is hydrophilic (polar) in nature the anchor will remain on the solid phase. Switching to a nonpolar solvent releases the organic substrate containing the anchor.

In one experimental setup[1] the hydrophobic matrix is RP silica gel (C18) and the anchor is acridone. Acridone is N-alkylated and the terminal alkene group is converted into an aldehyde by ozonolysis. This compound is bonded to RP silica gel and this system is subjected to a tandem sequence of organic reactions. The first reaction is a Barbier reaction with propargylic bromide in water (green chemistry) and the second reaction is a Sonogashira coupling. Substrates may vary in these sequences and in this way a chemical library of new compounds can be realized.

References

  1. Porzelle A, Fessner WD . 2005 . Reversible Substrate Anchoring: NC-SPOS as a Sustainable Approach to Solid-Supported Organic Synthesis . . 44 . 30 . 4724–4728 . 10.1002/anie.200462278 . https://archive.today/20110812231642/http://www3.interscience.wiley.com/cgi-bin/abstract/110544202/ABSTRACT . dead . 2011-08-12 . 2006-09-26 . abstract . 15968704. free .