Diversity-oriented synthesis and solid-phase organic synthesis under controlled microwave heating.
Diversity-oriented organic synthesis (DOS) and solid-phase organic synthesis (SPOS) are proven technologies for generating small molecule libraries for chemical genetics studies. Integration of controlled microwave heating with DOS and SPOS not only speeds up the library preparation process but also offers unique opportunities in tackling issues which are hardly addressed by thermal heating. Microwave-assisted synthesis is illustrated for (a) highly regioselective Wittig olefination of cycloalkanones by accurate regulation of temperature; (b) tandem Wittig-IMDA sequence toward stereochemical diversity of gamma-butyrolactones; (c) one-pot alkylation-amidation approach toward appendage diversity through use of building blocks; and (d) one-pot U-4CR-annulation strategy toward skeletal diversity via careful reaction design. Microwave-assisted solid-phase organic synthesis (MASPOS) is highlighted by incorporating with split-pool combinatorial synthesis (SPCS) of indole sulfonamides via a key on-resin Cu(II)- or Pd(II)-catalyzed heteroannulation under microwave heating. Design and fabrication of a novel diglycine-derived catlinker are described and its role in facilitating on-resin reaction is evaluated. A traceless synthesis of indole sulfonamides via microwave-assisted Cu(II)-catalyzed heteroannulation of the catlinker-tethered substrates is also given.
Dai
Wei-Min
WM
Laboratory of Asymmetric Catalysis and Synthesis, Department of Chemistry, Zhejiang University, Hangzhou, China. chdai@zju.edu.cn
Shi
Jianyu
J
D015107:4-Butyrolactone / Q000138:chemical synthesis; D000475:Alkenes / Q000737:chemistry; D000478:Alkylation; D000577:Amides / Q000737:chemistry; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D006361:Heating; D006571:Heterocyclic Compounds / Q000138:chemical synthesis; D007211:Indoles / Q000138:chemical synthesis; D007659:Ketones / Q000737:chemistry; D008670:Metals / Q000737:chemistry; D008872:Microwaves; D008956:Models, Chemical; D009930:Organic Chemicals / Q000138:chemical synthesis*; D012117:Resins, Synthetic / Q000737:chemistry; D013449:Sulfonamides / Q000138:chemical synthesis
D000475:Alkenes; D000577:Amides; D006571:Heterocyclic Compounds; D007211:Indoles; D007659:Ketones; D008670:Metals; D009930:Organic Chemicals; D012117:Resins, Synthetic; D013449:Sulfonamides; D015107:4-Butyrolactone