A convenient synthesis of cyclopentanones via rhodium(I)-catalyzed intramolecular hydroacylation of unsaturated aldehydes

Abstract

The rhodium(I)-catalyzed intramolecular hydroacylation of unsaturated aldehydes has been investigated. Three useful new catalyst systems have been developed. The catalysts are prepared by the addition of 2 equiv of tri-p-tolylphosphine, tri-p-anisylphosphine, or tris(p-dimethylaminophenyl)phosphine to chlorobis(cyclooctene)rhodium(l) in ethylene-saturated methylene chloride. 4,5-Unsaturated aldehydes afford good yields of substituted cyclopentanones. However, alkyl substitution in either the 2 or the 5 position substantially reduces the yield of ketone. Disubstitution in the 2 position gives rise to ethyl ketones instead. This procedure provides a valuable new route to spirocyclic and fused bicyclic ketones, but is not applicable to the synthesis of ketones of ring size other than five. Furthermore, it is tolerant of almost all important organic functionality except amines.

The synthesis and characterization of 3,3-disubstituted pent-4-enals and their 2,2-(trimethylenedithio)pent-4-enal precursors, including the X-ray crystal structure of (R)-3-ethyl-3-phenyl-2,2-(trimethylenedithio)pent-4-enal

“…Both E and Z isomers are present in 3a-3c, the isomer ratio being dictated by the usual steric interactions (see experimental section). Reaction [2] also proceeds smoothly at room temperatures and good yields of 4a-4c are obtained after ca. 5 days.…”

“…This feature makes 2-formyl-l,3-dithiane the thioacetal of choice in these reactions, as considerable difficulty was experienced in the purification of the liquid products derived from bis(-ethy1thio)acetal (these reactions were not pursued). From unsuccessful attempts to obtain other compounds of series 4, we have discerned two features associated with reactions [l] and [2] which limit their synthetic generality and that of Scheme 1 as a whole. Firstly, the use of ketones with bulky substitutents (e.g.…”

“…Secondly, the use of ketones with two aryl substituents (e.g. R = Ph, R' = p-MeOC6H4) enhances, following reaction [2], the rapid rearrangement of the series 4 product according to eq. [4].…”

“…Two methods have been reported (2) for the preparation of such compounds and the 2,3-disubstituted analogues. One method, of somewhat limited scope for synthesis of the 3,3-compounds, involves the conjugate addition of vinylcuprate(1) reagents to a,P-unsaturated aldehydes.…”

Diastereomers of the insect repellent 3-acetyl-2-(2′,6′-dimethyl-5′-heptenyl)oxazolidine. Isolation by high pressure liquid chromatography and characterization by 13C nuclear magnetic resonance spectroscopy

“…5-Methyl-4-hexenal was prepared from 2-methyl-3-buten-2-01 as described in the literature (18)(19)(20). This aldehyde (2.2 g, 0.02 mol) was reacted with ethanolamine (2.69 g, 0.044 mol) and acetic anhydride (4.5 g, 0.044 mol) as described for the preparation of 1.…”