The development of sulfamates as latent directed metalation groups. Total synthesis of schumanniophytine. Divergent synthesis of substituted chromone 3- and 8-carboxamides.

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Date
2007-12-04T19:14:51Z
Authors
Macklin, Todd Kristopher
Keyword
Organic Chemistry , Directed Ortho Metalation
Abstract
N,N-Diethyl-O-sulfamate (OSO2NEt2) has been established as a new directed metalation group (DMG). Its similarity to the established O-carbamate DMG has prompted investigation into its potential as a partner in transition metal-catalyzed cross coupling reactions with aryl organometallics with the intention to develop a new route to contiguously substituted aromatics. Furthermore, aryne formation of ortho-magnesiated O-sulfamates at higher temperatures can be trapped with furan to afford cycloaddition products having substitution patterns difficult to prepare by similar methods. Schumanniophytine is a structurally interesting alkaloid possessing anti-viral activity. Thus far, only a single synthesis has been reported which proceeds in poor yield and offers little opportunity for the synthesis of structurally diverse schumanniophytine derivatives. Herein we report the total synthesis of schumanniophytine by a directed ortho metalation (DoM) – cross coupling strategy using a key directed remote metalation (DreM) step. The synthesis proceeds in 10 steps with 24% overall yield, offering plenty of opportunity for structural variation. Naturally abundant chromone derivatives contain an array of biological activities. The ability to prepare differentially substituted chromones in a rapid manner is of great interest in medicinal chemistry. Reported is a general and divergent synthesis of chromone carboxamides, from easily prepared 2-but-2-ynoyl aryl O-carbamates. The reaction proceeds by carbamoyl translocation and anionic Fries rearrangement followed by Michael addition of the initially generated cumulenolate for which evidence is provided. Further metalation and borylation reactions of the synthesized compounds allow the regioselective construction of polysubstituted chromones.
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