Bicyclo[m.n.k]alkane Building Blocks as Promising Benzene and Cycloalkane Isosteres: Multigram Synthesis, Physicochemical and Structural Characterization

14 November 2023, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


Electrophilic double bond functionalization – intramolecular enolate alkylation sequence was used to obtain a series of bridged and fused bicyclo[m.n.k]alkane derivatives (i.e., bicyclo[4.1.1]octanes, bicyclo[2.2.1]heptanes, bicyclo[3.2.1]octanes, bicyclo[3.1.0]hexanes, and bicyclo[4.2.0]heptanes). The scope and limitations of the method were established, and applicability to the multigram synthesis of target bicyclic compounds was illustrated. Using the developed protocols, over 50 mono- and bifunctional building blocks relevant to medicinal chemistry were prepared. The synthesized compounds are promising isosteres of benzene and cycloalkane rings, which is confirmed by their physicochemical and structural characterization (pKa, LogP, and exit vector parameters (EVP)). Rules of thumb for the upcoming isosteric replacement studies were proposed.


Bicyclic compounds
Saturated compounds
Enolate alkylation


Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.
Comment number 1, Oleksandr Grygorenko: Jan 13, 2024, 13:42

The final version was published in Chemistry - A European Journal: