A Silicon Tether Approach for Addition of Functionalized Radicals to Chiral α-Hydroxyhydrazones:  Diastereoselective Additions of Hydroxymethyl and Vinyl Synthons

• Published in: Journal of organic chemistry 2004-02, Vol.69 (3), p.863-875
• Main Authors: Friestad, Gregory K, Massari, Sara E
• Format: Article
• Language: English
• Subjects: Aliphatic compounds; Chemistry; Exact sciences and technology; Organic chemistry; Preparations and properties
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo035405r

Stereocontrolled additions of hydroxymethyl and vinyl groups to chiral α-hydroxyhydrazones can be achieved by radical cyclizations using bromomethyl or vinyl radical precursors tethered via a temporary silicon connection. Tin-mediated 5-exo radical cyclization of α-hydroxyhydrazones using a silicon-tethered bromomethyl group, followed by oxidative removal of the tether, provides anti-2-hydrazino 1,3-diols in good yield. Tandem thiyl radical addition−cyclization of α-hydroxyhydrazones using a silicon-tethered vinyl group, followed by treatment with potassium fluoride, affords acyclic allylic anti-hydrazino alcohols in good yield. The thiyl addition−cyclization method has been successfully extended to the use of α,β-dihydroxyhydrazones without prior protection or hydroxyl differentiation. Diastereoselection in both reaction types increases with increasing A values of the appended groups, consistent with prediction by the Beckwith−Houk model for stereocontrol in 5-hexenyl radical cyclizations.