2,2,6,6-Tetramethylpiperidin-1-yloxycarbonyl: A Protecting Group for Primary, Secondary, and Heterocyclic Amines

Abstract

The 2,2,6,6-tetramethylpiperidin-1-yloxycarbonyl (Tempoc) protecting group is readily introduced by the reaction of amines with a new acyl transfer reagent, 4nitrophenyl (2,2,6,6-tetramethylpiperidin-1-yl) carbonate (NPTC). Tempoc has a reactivity profile that complements the commonly used t-butyloxycarbonyl (Boc) and benzyloxycarbonyl (Cbz) protecting groups. Deprotection can be achieved under mild reductive conditions with in situ generated Cu(I) species or by thermolytic cleavage at 135 °C. Mechanistic studies on the deprotection of Tempoc-indole suggest a combination of ionic and radical fragmentation pathways under thermal conditions.Letter pubs.acs.org/OrgLett

HFIP in Organic Synthesis

“…A small set of tert -butyl esters was examined using HFIP whereas tert -butyl carbonates substrates were deprotected using TFE. Similarly, the thermolytic deprotection of 2,2,6,6-tetramethylpiperidin-1-yloxycarbonyl (Tempoc) group on amines and indole was reported in HFIP at 135 °C …”

Asymmetric Total Synthesis and Biological Evaluation of (+)-Cycloclavine

“…In analogy to our route to (-)-cycloclavine, 11 we selected an asymmetric rhodium-catalyzed cyclopropanation of allene with a diazopropanoate active ester, followed by an aminolysis with 4-(methylamino)but-3-en-2-one, for the assembly of the key precursor for the IMDAMC reaction. After installing the enone in the six-membered ring by a Diao-Stahl ketone dehydrogenation, 14 the thermally removable Tempoc group for amine protection 15 would be used to stabilize an aminomethyllithium reagent and favor enone 1,2addition versus lactam ring opening. The final indole ring fusion was envisioned to be accomplished by the IMDAF cycloaddition.…”

Application of Dimedone Enamines as Protecting Groups for Amines and Peptides

“…Organic synthesis has not evolved to a point where functional group protection and deprotection are not necessary for the construction of any desired organic molecules or natural products . Hence, the development of new protecting methodologies for frequently encountered functional groups, such as amines, remains to be an attractive task for organic chemists . The commonly seen carbamate protecting groups such as Boc, Cbz, and Fmoc have occupied a prominent position in amine protection.…”