Control of Site of Lithiation of 3-(Aminomethyl)pyridine Derivatives

Journal Article

Smith, Keith . 2013

• نوع عمل المنشور: Research
• رابط المنشور على الويب: https://www.thieme-connect.com/ejournals/abstract/10.../s-0033-1338547
• المجلة \ الصحيفة: Synthesis
• رقم العدد: 24
• رقم الإصدار السنوي: 35
• الصفحات: 3426–3434

مستخلص المنشور

Lithiation of N-(pyridin-3-ylmethyl)pivalamide, tert-butyl N-(pyridin-3-ylmethyl)carbamate and N'-(pyridin-3-ylmethyl)-N,N-dimethylurea with three mole equivalents of t‑butyllithium in anhydrous THF at -78 °C takes place on the nitrogen and on the ring at the 4-position. The dilithium reagents thus obtained react with various electrophiles to give the corresponding substituted derivatives in high yields. On the other hand, regioselective side-chain lithiation occurs with LDA (3.3 mole equivalents) at -20 to 0 °C. A mixture of ring and side-chain substitution products is obtained with n-butyllithium as the lithium reagent. Treatment of one of the ring substituted products with trifluoroacetic anhydride in dichloromethane under reflux conditions led to formation of the corresponding 1H-pyrrolo[3,4-c]pyridine in high yield.