A new, efficient and stereoselective synthesis of tricyclic and tetracyclic compounds by samarium diiodide induced cyclisations of naphthyl-substituted arylketones--an easy access to steroid-like skeletons.
In this report, we present the application of samarium diiodide induced cyclisations of naphthyl-substituted ketones towards an easy and stereoselective access to tri- and tetracyclic-functionalised compounds. Typical naphthalene derivatives were studied to investigate the scope and limitations of this novel cyclisation process. The model substrates studied demonstrate that the samarium ketyl cyclisations are essentially restricted to the formation of six-membered rings. The diastereoselectivity of these reactions is strongly influenced by the connection of the alkyl side chain to the naphthalene core. Gamma-naphth-1-yl-substituted ketones furnished cyclisation products, such as 17 or 22-26, as single diastereomers, whereas gamma-naphth-2-yl-substituted precursors gave mixtures of diastereomers--as demonstrated by the conversion of model compound 10 into tricyclic products 18 a/18 b, or that of cyclohexanone derivative 33 into tetracyclic diastereomers 34 a/34 b. Cyclic ketones as ketyl precursors furnished steroid-like tetracyclic skeletons; however, due to the cis/cis fusion of rings B/C and C/D these products have an "unnatural" bowl-like shape. Several of the cyclisation products have been identified by X-ray analyses, which not only proved the constitutions, but also the relative configurations and the preferred conformations. Steroid analogue 23 was subjected to subsequent transformations, which demonstrate that the styrene-like double bond of such compounds can be used for further structural diversification. First attempts to synthesise related azasteroids by incorporating nitrogen atoms into the ketone moiety are also reported. Thus, pyrrolidine derivatives 44 and 47 as well as piperidine derivatives 50 and 52 were subjected to samarium diiodide induced cyclisations. The expected tetracyclic products 48, 49 a/49 b, 51 and 53 a/53 b were obtained in moderate to good yields. The stereoselectivities observed follow the rules already established for the all-carbon precursors. The resulting products, bearing a nitrogen atom in ring D, are interesting azasteroid analogues with "unnatural" configuration.
Aulenta
Francesca
F
Institut für Chemie und Biochemie, Freie Universität Berlin, Takustrasse 3, 14195 Berlin, Germany.
Berndt
Mathias
M
Brüdgam
Irene
I
Hartl
Hans
H
Sörgel
Sebastian
S
Reissig
Hans-Ulrich
HU
D000478:Alkylation; D001372:Aza Compounds / Q000737:chemistry*; D003500:Cyclization; D007454:Iodides / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry*; D047028:Macrocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D009281:Naphthalenes / Q000737:chemistry*; D009584:Nitrogen / Q000737:chemistry; D011759:Pyrrolidines / Q000737:chemistry; D012493:Samarium / Q000737:chemistry*; D013237:Stereoisomerism; D013256:Steroids / Q000737:chemistry*
D001372:Aza Compounds; D007454:Iodides; D007659:Ketones; D047028:Macrocyclic Compounds; D009281:Naphthalenes; D011759:Pyrrolidines; D013256:Steroids; C031721:naphthalene; D012493:Samarium; C409809:samarium diiodide; C032519:pyrrolidine; D009584:Nitrogen