Direkte, Bor-vermittelte N-Funktionalisierung von Nitroverbindungen

  • Direct, boron-mediated N-functionalization of nitro compounds

Eckert, Raphael; Niggemann, Meike (Thesis advisor); Patureau, Frédéric (Thesis advisor)

Aachen : RWTH Aachen University (2021)
Dissertation / PhD Thesis

Dissertation, RWTH Aachen University, 2021

Abstract

The direct use of nitro groups to synthesize amines is a more step economic alternative to traditional functionalization strategies and has received increased attention in recent years. The biggest limitation in this field is the absence of a transition-metal catalyzed cross-coupling. Hence, a stereoselective C–N-coupling to introduce the nitro group’s nitrogen atom into an organic scaffold has not been reported, yet. In addition, the nitro group has been coupled mostly with nucleophiles. Reductive couplings are rare and restricted to aromatic nitro groups. Ultimately, the diboron-mediated electrophilic amination developed in the Niggemann group offers direct access to a variety of aminoboranes which were formerly hard or impossible to synthesize. These are interesting synthetic scaffolds for the difunctionalization of double and triple bonds.In this doctoral thesis these starting points were addressed to advance the field of direct nitro functionalization:1)It was shown that aminoboranes synthesized by the protocol of Niggemann et al. can be used for an aminoboration of triple bonds. 2)Based on the diboron-mediated functionalization of nitro groups the reductive coupling of nitro compounds with organo halides was expanded to the important class of aliphatic nitro compounds. This was possible in a catalyst-free fashion by utilizing a nitrenoid intermediate which was confirmed in mechanistic studies. 3)The first Cu-catalyzed coupling of a nitro group was realized using an allylic nucleophile for the first time in a C–N coupling. The excellent selectivity for the highest substituted carbon derives from an inverted ligand field in the key complex. In the future this new reaction possibly enables the stereoselective coupling of a nitro group with a C-nucleophile. The conducted studies showed that – esp. in the reductive coupling and the Cu-catalyzed reaction – that boron as a diboronic reductant and in boronic acid derivatives as substrates can play a crucial role in stabilizing the nitro reduction cascade. Thereby it contributes to tolerating aliphatic nitro compounds. This makes boronic acid derivates excellent substrates in direct nitro funcitonalizations.

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