Transition-Metal Controlled Diastereodivergent Radical Cyclization/Azidation Cascade of 1,7-Enynes

Abstract

A strategy for achieving diastereodivergent azidations of enynes has been developed, employing azide transfer from the M-N3 complex to alkyl radicals. Following this concept, the diastereoselectivity has been switched by modulating the transition metals and the ligands. The Mn(III)-mediated radical cyclization/azidation cascade of 1,7-enynes afforded trans-fused pyrrolo[3,4-c]quinolinones, whereas the Cu(II)/bipyridine system gave cis-products.

Metal‐Catalysed Azidation of Organic Molecules

“…Selective synthesis of both cis ‐ and trans ‐pyrrolo[3,4‐ c ]quinolinones through the use of two sets of catalysts and ligand systems was reported by Wan and co‐workers . In the transformation of N ‐sulfonyl‐tethered 1,7‐enynes the Mn(OAc) 3 ‐catalysed reaction yielded the trans product with high selectivity, whereas the Cu‐catalysed system gave the cis product with high selectivity.…”

Potassium‐Persulfate‐Promoted Regioselective Azidation/Cyclization of 1,6‐Enynes

“…On the basis of these mechanistic studies and literature reports, we propose herein a plausible mechanism for this azidation cyclization in Scheme . At the beginning, an azide radical is generated by oxidation of TMSN 3 in the presence of K 2 S 2 O 8 .…”

“…In 2015, Song, Li and co‐workers demonstrated a novel azide radical mediated annulation/azidation of enynes with azido‐benziodoxolone in the presence of Cu(OAc) 2 (Scheme a) . Later, Wan group disclosed a transition‐metals (Mn‐ and Cu‐) and ligand controlled diastereodivergent radical annulation/azidation of 1,7‐enynes with TMSN 3 (Scheme b) . Although these protocols are efficient, they all used transition‐metal catalysts, such as Cu or Mn reagents.…”

“…At the beginning, an azide radical is generated by oxidation of TMSN 3 in the presence of K 2 S 2 O 8 . Subsequently, the addition of the azide radical to the alkene moiety of 1,6‐enyne 1 a provides an alkyl radical intermediate I . Further radical cyclization to the alkyne moiety furnishes the vinyl radical intermediate II .…”

“…Subsequently, the addition of the azide radical to the alkene moiety of 1,6‐enyne 1 a provides an alkyl radical intermediate I . Further radical cyclization to the alkyne moiety furnishes the vinyl radical intermediate II . Finally, intermediate II abstracts a hydrogen atom from the solvent or water to afford final product 3 a …”