Organic Chemistry: Current Research
Open Access
ISSN: 2161-0401
+44 1478 350008
ISSN: 2161-0401
+44 1478 350008
Hidefumi Nakatsuji and Yoo Tanabe
Kwansei Gakuen University, Japan
Scientific Tracks Abstracts: Organic Chem Curr Res
The stereo-controlled preparation of ubiquitous (E)- and (Z)-?±,?²-unsaturated esters 1 is pivotal in organic syntheses, because of their wide distribution in natural products, pharmaceuticals, and supramolecules as key structural building blocks. Consistent with our continued interest in finding a methodology directed towards natural product synthesis and process chemistry, we have developed parallel and practical methods for the stereocomplementary preparation of both of â??multiâ?-substituted (E)- and (Z)-1 from readily available ?²-oxoesters 2 and 2â??. The present protocol is composed of sequential (E)- and (Z)-stereocomplementary enol tosylations and stereoretentive cross-coupling reactions (Types I and II). The salient advantageous features are as follows. (i) Various ?²-keto or ?±-formyl esters 2 and 2â?? are practically available using bases-promoted and Ti-Claisen condensations. (ii) Both (E)- and (Z)- enol tosylates 3 and 3â?? derived from respective 2 and 2â?? are prepared in (E)- and (Z)-stereocomplementary manner by using accessible, robust, and bench-top handling TsClâ??N-methylimidazole (NMI) or TsClâ??Me2(CH2)nNMe2 (n=2, 6) reagents. NMI or Me2(CH2) nNMe2 is a key potential activator for the sulfonylation. A careful 1H NMR monitoring experiment (â??40?ºC in CD3CN) revealed that TsCl coupled with NMI or TMEDA formed active N-sulfonylammonium intermediates. (iii) High and consistent substrategenerality (>100 examples: Suzuki-Miyaura, Negishi, Sonogashira, Kochi-F?¼rstner) is demonstrated. (iv) The parallel syntheses of (E)- and (Z)-1 and 1â?? are performed by using a pair of 2 and 2â??. (v) The obtained (E)- and (Z)-?±,?²-unsaturated ester scaffolds can be transformed into various (E)- and (Z)-stereodefined known and novel olefins. To demonstrate the utility of the present method, expeditious the first â??parallelâ? syntheses of all four (E)- and (Z)-Zimelidines 4 (5 steps, 33% and 45% overall yield, 80% and 82% average yield) and Tamoxifens 5 (8 steps, 58% and 57% overall yield, 93% and 84% average yield), which are highly representative olefin motifs of pharmaceuticals, was accomplished.
Hidefumi Nakatsuji received his BS degree (2005) and his PhD degree (2010) from Kwansei Gakuin University under the direction of Professor Yoo Tanabe. He moved to Nagoya University (Professor Kazuaki Ishihara’s group) and studied as JSPS Post-doctoral Fellowship and CREST Project Researcher until 2014. He was promoted as an Assistant Professor of the Tanabe’s group. His research interests are development of chiral phosphine and phosphine oxide organocatalysts for a MCR type cyclization and of condensation reactions for cost-effective reactions directed for process chemistry.
Email: nakatsuji@kwansei.ac.jp