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Synthesis 2010(24): 4242-4250  
DOI: 10.1055/s-0030-1258301
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Lithium Naphthalenide-Induced Reductive Alkylation and Addition of Aryl- and Heteroaryl- Substituted Dialkylacetonitriles

Jing-Po Tsaoa, Ting-Yueh Tsaia, I-Chia Chenb, Hsing-Jang Liu*a, Jia-Liang Zhu*c, Sheng-Wei Tsaoc
a Department of Chemistry, National Tsing Hua University, Hsinchu 300013, Taiwan, R.O.C.
e-Mail: hjliu@mx.nthu.edu.tw;
b Department of Cosmetic Applications and Management, Cardinal Tien College of Healthcare and Management, Taipei, Taiwan, R.O.C.
c Department of Chemistry, National Dong Hwa University, Hualien 974, Taiwan, R.O.C.
Fax: +886(3)8633570; e-Mail: jlzhu@mail.ndhu.edu.tw;
Further Information

Publication History

Received 14 August 2010
Publication Date:
14 October 2010 (online)

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Abstract

Lithium naphthalenide (LN)-induced reductive alkylation/addition reactions of aryl-, pyridyl-, and 2-thienyl-substituted dialkylacetonitriles have been investigated. Upon treatment with LN in THF at -40 ˚C, both aryl and pyridyl precursors could undergo the reductive decyanation smoothly, and the in situ generated carbanions could be readily trapped by alkyl halides, ketones, aldehydes, or even oxygen to afford a wide range of functionalized aromatic derivatives bearing a newly established quaternary carbon. To effect the desired reductive alkylation of 2-thienyldialkylacetonitriles, a much lower temperature such as -100 ˚C was required. Also with these substrates, an interesting ring-opening/S-alkylation process was observed when the reductive alkylation were performed at -78 ˚C to give 1-alkylsulfanyl-1,3,4-trienes. A mechanistic discussion is given for this observation.

Key words

reductive alkylation - reductive addition - reductive decyanation - nitriles - lithium naphthalenide - aryl derivatives - heteroaryl derivatives - substituted 1,3,4-trienes

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The stereogeometry of 5b-d remains to be determined.