Free-radical based cycloalkanol synthesis and annulation from thioacetal precursors

Abstract

A general procedure for the synthesis of diverse cyclopentanols via free-radical cyclization of unsaturated 1,3-oxathiolanes and I ,3-oxathiolan-5-ones is described. The scope of these reactions, including preliminary rate studies that indicate that the 1,3-oxathiolan-5-ones cyclize at a useful rate (I .4 X lo6 M-I S -I at 80°C), has been examined. This permits the rapid assembly, by intramolecular annulation, of various additional ring systems, including bicyclo[3.

Samarium Diiodide-Promoted Intramolecular Radical Cyclization of (η4-Diene)Fe(CO)3 Complexes Bearing Keto Side Chains

“…The chemical shift of 69.6 ppm in 13 was assigned to the tertiary alcohol carbon. The observed upfield chemical shift of 69.6 ppm demands the cis relationship of the hydroxyl group and the adjacent alkyl substituents in the five-membered ring, and the assignment is consistent with the report found in the literature . The origin of different stereochemical preferences observed for the formation of bicyclic compounds 11 and 12 and the bicyclo[4.3.0]nonanone derivative 13 was suggested as follows.…”

“…Several examples of radical cyclization of acyclic diene−iron complexes are summarized in Table (entries 6−10). The stereochemical assignments of 22 − 26 were provided by comparison of their 13 C NMR chemical shifts of the tertiary alcohol carbon with the data of cis -1,2-dialkylcyclopentanol and -cyclohexanol derivatives formed in the literature. , The assignment of the stereochemistry of 22 − 26 is consistent with the reaction pathway proposed for the cyclic precursors (entries 1 and 2, Table ). It is important to mention that the isolation of cyclohexanol derivative 26 (73.3 ppm for the tertiary carbinol center) 9 with the cis -1,2-dialkyl substituent is consistentent with the proposed reaction pathway stated in Scheme .…”

Thiols, thioethers, and related compounds as sources of C-centred radicals

“…To address this issue, the same authors investigated the generation of a-acyloxyl radicals from the related 1,3-oxathiolan-5-ones. 171,172 The precursors were easily prepared from aldehydes and ketones and b-mercaptoacetic acid. The cyclization of 1,3-oxathiolan-5-ones possessing an alkenyl side chain was achieved by slow addition of Bu 3 SnH and AIBN.…”

“…Under their reaction conditions, intermolecular trapping of the a-acyloxy radical with the allyltin reagent competes favourably with the cyclization reaction. 171,172 Keck and co-workers stressed the advantages of hemithioketals in terms of ease of preparation and stability compared to the corresponding a-haloethers in allylation reactions at the anomeric centre of glycosides (Scheme 80, eqn (a)). 176 Under modified Keck' allylation conditions, Kano and co-workers were able to access optically pure 1,2-amino alcohols from 5-(phenylthio)oxazolidin-2-ones derived from (S)-amino acids (Scheme 80, eqn (b)).…”

A Two-Step Synthesis of 3,4-Disubstituted Piperidines from Acyclic Precursors through Tetrahydropyridine Intermediates

“…9 In support of these assignments, the expected g-gauche effects were observed in the 13 C NMR resonances of the piperidine ring C3 and C4, which were deshielded in the trans-isomers relative to the more congested cis counterparts. 7,[10][11][12][13] Synthetic advantage can be also taken from the choice between two alternative reducing methods for the enamine double bond. For example, the hydride method allowed chemoselective enamine reduction in the presence of a second C=C bond (entry 5), whereas hydrogenation conditions applied to benzyl-protected enamines 9 (R 2 = Bn) resulted in both double bond reduction and debenzylation leading to formation of secondary piperidines 11 (Scheme 5).…”