Concise and Highly Stereoselective Synthesis of β,β-Disubstituted α,β-Unsaturated Esters

Minoru Ozeki; Mizuki Tsuda; Serina Yamanouchi; Momoe Yamakawa; Kanako Fukuda; Hirotaka Sasa; Takuya Matsumoto; Aya Niki; Maaya Nobata; Takashi Shigeta; Tetsuya Kajimoto; Kenji Arimitsu; Shinzo Hosoi; Hiroki Iwasaki; Naoto Kojima; Ikuo Kawasaki

doi:10.1248/cpb.c24-00751

Note

Concise and Highly Stereoselective Synthesis of β,β-Disubstituted α,β-Unsaturated Esters

Minoru Ozeki , Mizuki Tsuda, Serina Yamanouchi, Momoe Yamakawa, Kanako Fukuda, Hirotaka Sasa, Takuya Matsumoto, Aya Niki, Maaya Nobata, Takashi Shigeta, Tetsuya Kajimoto, Kenji Arimitsu, Shinzo Hosoi, Hiroki Iwasaki, Naoto Kojima, Ikuo Kawasaki

Author information

Minoru Ozeki Corresponding author
Faculty of Pharmaceutical Sciences, Mukogawa Women’s University, 11–68 Koshien Kyuban-cho, Nishinomiya, Hyogo 663–8179, Japan
Mizuki Tsuda
Faculty of Pharmaceutical Sciences, Mukogawa Women’s University, 11–68 Koshien Kyuban-cho, Nishinomiya, Hyogo 663–8179, Japan
Serina Yamanouchi
Faculty of Pharmaceutical Sciences, Mukogawa Women’s University, 11–68 Koshien Kyuban-cho, Nishinomiya, Hyogo 663–8179, Japan
Momoe Yamakawa
Faculty of Pharmaceutical Sciences, Mukogawa Women’s University, 11–68 Koshien Kyuban-cho, Nishinomiya, Hyogo 663–8179, Japan
Kanako Fukuda
Faculty of Pharmaceutical Sciences, Mukogawa Women’s University, 11–68 Koshien Kyuban-cho, Nishinomiya, Hyogo 663–8179, Japan
Hirotaka Sasa
Faculty of Pharmaceutical Sciences, Mukogawa Women’s University, 11–68 Koshien Kyuban-cho, Nishinomiya, Hyogo 663–8179, Japan
Takuya Matsumoto
Faculty of Pharmaceutical Sciences, Mukogawa Women’s University, 11–68 Koshien Kyuban-cho, Nishinomiya, Hyogo 663–8179, Japan
Aya Niki
Faculty of Pharmaceutical Sciences, Mukogawa Women’s University, 11–68 Koshien Kyuban-cho, Nishinomiya, Hyogo 663–8179, Japan
Maaya Nobata
Faculty of Pharmaceutical Sciences, Mukogawa Women’s University, 11–68 Koshien Kyuban-cho, Nishinomiya, Hyogo 663–8179, Japan
Takashi Shigeta
School of Food and Nutritional Sciences, University of Shizuoka, 52–1 Yada, Suruga-ku, Shizuoka 422–8526, Japan
Tetsuya Kajimoto
College of Pharmaceutical Sciences, Ritsumeikan University, 1–1–1 Noji-higashi, Kusatsu, Shiga 525–8577, Japan
Kenji Arimitsu
Faculty of Pharmacy, Osaka Ohtani University, 3–11–1 Nishikiori-kita, Tondabayashi, Osaka 584–8540, Japan
Shinzo Hosoi
Kyoto Pharmaceutical University, 1 Shichono-cho, Misasagi, Yamashina-ku, Kyoto 607–8414, Japan
Hiroki Iwasaki
Kyoto Pharmaceutical University, 1 Shichono-cho, Misasagi, Yamashina-ku, Kyoto 607–8414, Japan
Naoto Kojima
Faculty of Pharmaceutical Sciences, Nagasaki International University, 2825–7 Huis Ten Bosch Machi, Sasebo, Nagasaki 859–3298, Japan
Ikuo Kawasaki Corresponding author
Faculty of Pharmaceutical Sciences, Mukogawa Women’s University, 11–68 Koshien Kyuban-cho, Nishinomiya, Hyogo 663–8179, Japan

Keywords: stereoselective synthesis, β,β-disubstituted α,β-unsaturated ester, aldol reaction, acetylation reaction, elimination reaction

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Supplementary material

2025 Volume 73 Issue 3 Pages 264-267

DOI https://doi.org/10.1248/cpb.c24-00751

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Abstract

Building on our previously reported techniques, we developed a concise and highly stereoselective synthesis method for β,β-disubstituted α,β-unsaturated esters. This synthesis comprises 3 reactions: the aldol reaction of acetic ester derivatives with ketones, the acetylation of tert-alcohols, and an elimination reaction utilizing 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). During the acetylation process, acetic anhydride and 4-dimethylaminopyridine (DMAP) facilitated the smooth acetylation of bulky tert-alcohols; however, employing DBU as a base reduced the yields. Additionally, the removal of excess DMAP effectively suppressed the formation of unwanted byproducts during the elimination step.

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