Total Synthesis of (±)-Cytisine

Abstract

[reaction:see text] The nicotine partial agonist cytisine was prepared in five steps featuring an "in situ" Stille or Suzuki biaryl pyridine coupling. Differentiation of the pyridyl rings was accomplished via selective benzylation and then reduction of a pyridinium ring. The penultimate diazabicyclo[3.3.1]nonane intermediate was obtained with high diastereoselectivity. A similar sequence has been employed for the synthesis of novel derivative 9-methoxycytisine.

A General and Efficient Method for the Suzuki–Miyaura Coupling of 2‐Pyridyl Nucleophiles

“…[9] Although 2-pyridylborates have been used in SuzukiMiyaura reactions, the cross-coupling processes result in only poor to modest yields of the desired biaryl product. [12] However, when lithium triisopropyl 2-pyridylborate (A) was employed as the nucleophile, the desired product could be obtained in 85 % yield with 100 % conversion of the aryl halide (Table 1, entry 5). Although A is not yet commercially available, it is stable under an argon atmosphere for up to a month, and it can be prepared in near quantitative yield from 2-bromopyridine by lithium-halogen exchange and immediate in situ quenching of the resulting anion with triisopropylborate.…”

Indolizidine and quinolizidine alkaloids

“…96 After reduction of the alkyne and removal of the THP protecting group, the alcohol 212 was treated with methanesulfonyl chloride. 97 Remarkably, the coupled product 219 could be isolated in 40-50% yields, with only traces of the homo-coupled bipyridyl product from 218, and none at all from 217. b New alkaloids (tentative).…”

Versatile tools in the construction of substituted 2,2′-bipyridines—cross-coupling reactions with tin, zinc and boron compounds

“…132 In 2000 a total synthesis of (AE)-cytisine has been reported, where the authors prepared a 2-pyridylboronate in situ for a subsequent cross-coupling reaction with a 3-pyridyl bromide, yielding a 2,3 0 -bipyridine. 133 Since then efforts have been made to prepare significantly more stable 2-pyridylboron precursor compounds that can be efficiently used in cross-coupling reactions. A compilation of synthesised compounds is displayed in Scheme 22.…”