27068-65-1Relevant articles and documents
Improved synthesis of 2,4,6-trialkylpyridines from 1,5-diketoalkanes: The total synthesis of Anibamine
Miyakoshi, Takeru,Konno, Hiroyuki
, p. 2896 - 2905 (2019)
Many pyridine syntheses have been developed to date. In this study, we focused on pyridine synthesis with 1,5-diketone derivatives and hydroxylamine. Treatment of simple 1,5-diketoalkanes and hydroxylamine in basic or acidic conditions gave aldol adducts without any pyridine compounds. However, by screening the reaction conditions, we found that acidic conditions produced via the formation of oxime intermediates derived from 1,5-diketoalkanes allowed the formation of the corresponding pyridine derivatives. This is the first example of 2,4,6-trialkylpyridine synthesis from quite simple 1,5-diketoalkanes. In order to demonstrate the utility of the reaction, we demonstrated the synthesis of pyridine derivatives and the total synthesis of a 6-substituted pyridyl-natural product, anibamine. This was achieved by following the above methodology using a reported compound as the starting material to give the product in 12% yield.
Simple and Clean Photo-induced Methylation of Heteroarenes with MeOH
Liu, Wenbo,Yang, Xiaobo,Zhou, Zhong-Zhen,Li, Chao-Jun
supporting information, p. 688 - 702 (2017/05/15)
Heteroarene methylation utilizing a cheap and safe methylation source without involving transition metals represents an important yet challenging objective. Here, a simple and clean catalyst-free protocol for the methylation of various heteroarenes (including six- and five-membered types) is described under light irradiation. This protocol employs cheap, readily available, and abundant MeOH as both the solvent and the methylation source. It was found that adding dichloromethane (DCM) as a co-solvent could significantly increase the yield of the methylation products. Heteroarenes bearing various functional groups could be methylated and tri-deuteromethylated successfully. Deuterium labeling studies suggested that the newly generated methyl group in the products consisted of two hydrogens from the methyl group and one hydrogen from the OH group in MeOH.
Alcohols as alkylating agents in heteroarene C-H functionalization
Jin, Jian,MacMillan, David W. C.
, p. 87 - 90 (2015/09/15)
Redox processes and radical intermediates are found in many biochemical processes, including deoxyribonucleotide synthesis and oxidative DNA damage. One of the core principles underlying DNA biosynthesis is the radical-mediated elimination of H2O to deoxygenate ribonucleotides, an example of 'spin-centre shift', during which an alcohol C-O bond is cleaved, resulting in a carbon-centred radical intermediate. Although spin-centre shift is a well-understood biochemical process, it is underused by the synthetic organic chemistry community. We wondered whether it would be possible to take advantage of this naturally occurring process to accomplish mild, non-traditional alkylation reactions using alcohols as radical precursors. Because conventional radical-based alkylation methods require the use of stoichiometric oxidants, increased temperatures or peroxides, a mild protocol using simple and abundant alkylating agents would have considerable use in the synthesis of diversely functionalized pharmacophores. Here we describe the development of a dual catalytic alkylation of heteroarenes, using alcohols as mild alkylating reagents. This method represents the first, to our knowledge, broadly applicable use of unactivated alcohols as latent alkylating reagents, achieved via the successful merger of photoredox and hydrogen atom transfer catalysis. The value of this multi-catalytic protocol has been demonstrated through the late-stage functionalization of the medicinal agents, fasudil and milrinone.
