Creation of general stereochemistry by an optically active trisubstituted cubic carbon skeleton

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K19120
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Organic chemistry and related fields
• Research Institution: Kyoto University
• Principal Investigator: MATSUBARA Seijiro 京都大学, 工学研究科, 教授 (90190496)
• Project Period (FY): 2017-06-30 – 2019-03-31
• Keywords: キュバン / 立体選択的 / ファーマコフォア / 有機亜鉛 / サイト選択的 / 電荷シフト結合

Outline of Final Research Achievements

The iodine-metal exchange reaction on cubane was examined using various lithium organozincates. Among these, the dianionic zincate gave the best results. The resulting cubyl metal species could be converted into various cubane derivatives via addition reactions with electrophiles, such as an organohalide or aldehyde. The potential functional group tolerability of organozincates lends this protocol to the synthesis of polyfunctionalized cubane derivatives. Thus obtained 4-deuteriocubane-N,N-diisopropylcarboxamide with the bulky N-bromoamide reported by Alexanian, gave 4-deuterio-3,5-dibromocubane-N,N-diisopropylcarboxamide in 70% yield. This selective formation of the prochiral dibromide provided a route to the preparation of a chiral cubane by selective functionalization of a C-Br bond with the dianionic zincate. We found a route to prepare 1,3,5-trisubstituted cubanes.

Free Research Field

有機合成化学

Academic Significance and Societal Importance of the Research Achievements

複数の官能基が分子骨格に位置・立体選択的に配置された分子は，生理活性や有機分子触媒としての能力を示すことが多い。しかし，そのような多置換の分子の合成は，例えば直鎖炭素骨格に三つの官能基を置換した場合でも光学異性体を含めると８つの立体異性体があり，その選択的合成は困難が伴う。本研究では，高い対称性を有するキュバンに注目した。このことは，立体選択的合成上非常に有利になる。このようなCubaneは，新規な薬品の基本骨格としての可能性が大きい。