A General, Diastereoselective Synthesis of Highly Functionalized Bicyclo[n.3.1]alkane Systems Based on an Anionic Domino Reaction of α‐Nitrocycloalkanones

Abstract

Keywords: Bicyclic compounds / Domino reactions / Michael addition / Aldol reactions / DiastereoselectivityThe base-promoted Michael-aldol anionic domino reactions of cyclic α-nitro ketones and α,β-unsaturated aldehydes afforded bicyclo[n.3.1]alkanone systems of seven different ring sizes (n = 3-9), normally in excellent yields. This can be considered the first general method for the synthesis of this type of carbocycle. Furthermore, up to four stereocentres are generated, three of which are contiguous and include a function-

Michael Additions in Aqueous Media: “On‐Water” and “In‐Water” Processes from α‐Nitro Ketones and Their Anions

“…[14] Although these reactions often exhibit significant rate enhancements relative to similar reactions in organic solvents, they have received relatively little synthetic attention outside of a few specialized fields. These are a very important class of synthetic intermediates [19] and have been employed as precursors to a wide variety of pharmacologically valuable compounds including ω-nitroalcohols and spiroketals, [20] β-nitroalcohols, [21] bridged macrolactones, [22] bicyclo-[n.3.1]alkanes [23] and their benzoand naphtho-fused derivatives, [24] indanes [25] and macrocarbocycles. [15] To the best of our knowledge, there is only one example of an uncatalysed "on-water" Michael reaction, consisting of the dehydrogenative coupling between indoles and benzoquinone, a very reactive Michael acceptor, [16] although some aza-Michael "on-water" reactions are also known.…”

A systematic 1H‐ and 13C‐NMR spectral analysis of bicyclo[n.3.1]alkanone systems: Determination of the relative configuration of the stereogenic centres and conformation of the six‐membered ring

“…The conformational and configurational conclusions outlined above agree with X‐ray diffraction data previously obtained for compounds 11 and 18 …”

“…While the NMR‐based structural study of derivatives of the bicyclo[3.2.1]alkane system has been described in the literature, to our knowledge, there is no account of the systematic application of these methods to the study of a full series of bicyclo[n.3.1]alkane derivatives, with varying values of n , probably owing to the lack of a general synthetic access to these systems. We describe here the study by 1 H‐, 13 C‐, and 2D‐NMR techniques of compounds 2a ‐ 18 , obtained from α‐nitrocyclalkanones 1 by our previously published method, and the application of spectral data to their conformational and configurational assignment. The minor diastereomers 2b and 19 were also studied for comparison purposes (Figure ).…”

Synthesis of a D Ring‐Functionalized Derivative of the Epiwelwistatin Tetracyclic Core

“…Compound A would be obtained by C‐2 oxidation of the corresponding indole B . The preparation of these intermediates would result from the generation of the bicyclic system through an anionic domino process that combines individual Michael and aldol steps14,15 to generate the desired tetracyclic system that starts from compound C . Finally, these materials should be available by the ring‐expansion of D , which is a known compound that has been employed as the starting material for the synthesis of ergot alkaloids and is known as Kornfeld's ketone (see Scheme ).…”