Abstract
A method for the synthesis of substituted cycloalkanes was developed using diols and secondary alcohols or ketones via a cascade hydrogen borrowing sequence. A non-noble and air-stable manganese catalyst (2 mol %) was used to perform this transformation. Various substituted 1,5-pentanediols (3-4 equiv) and substituted secondary alcohols (1 equiv) were investigated to prepare a collection of substituted cyclohexanes in a diastereoselective fashion. Similarly, cyclopentane, cyclohexane, and cycloheptane rings were constructed from substituted 1,4-butanediol, 1,5-pentanediol, and 1,6-hexanediol, and sterically hindered ketones following a (4 + 1), (5 + 1), and (6 + 1) strategy, respectively. This reaction provides an atom economic methodology to construct two C-C bonds at a single carbon center generating high-value cycloalkanes from readily available alcohols as feedstock using an earth-abundant metal catalyst.
Highlights
Cycloalkanes are ubiquitous structural motifs in natural products, pharmaceuticals, or materials.[1]
Cycloisomerization followed by hydrogenation can be considered as a possible synthetic route.[11]. These strategies require the dedicated synthesis of very specific starting materials containing the functional groups in perfect arrangement to allow for the cyclization step
Akhtar and co-workers reported the synthesis of substituted cyclohexanes using sterically hindered 1-(2,3,4,5,6pentamethylphenyl)ethanone and diols applying a noblemetal iridium catalyst.[15]
Summary
While the reaction with 1-phenyethanol 2a resulted in alcohol 4a as product (Table 1, entry 11), the coupling of sterically more hindered 1-mesitylethanol 8 with 1,5-pentanediol 3a resulted in the selective formation of ketone 9 as product with 37% isolated yield (Scheme 2). Proposed Reaction Sequence and the Role of the Mn-Catalyst for the Synthesis of Substituted Cycloalkanes from Diols and Secondary Alcohols rationalized assuming that ketone 5b is formed from 8 as intermediate, but the C O group in the product cannot be rehydrogenated due to steric hindrance.
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