Radical Cyclizations of Acylgermanes. New Reagent Equivalents of the Carbonyl Radical Acceptor Synthon

Abstract

An in depth study of the capability of acylgermanes to function as acceptors in radical cyclizations is reported. Radicals add to acylgermanes, and rapid fragmentation of the resulting α-germylalkoxy radicals provides ketones and germyl radicals. The germyl radicals in turn propagate the chain by addition or abstraction, so the reaction occurs by a unimolecular chain transfer (UMCT) process. In contrast, acylsilanes also function as radical acceptors, but they do not participate in UMCT processes because a “radical-Brook” rearrangement intervenes. Cyclizations in 5-exo and 6-exo modes show good to excellent scope, and rate constants for cyclization can be varied over 2 orders of magnitude by changing the germanium substituents. Acyltriarylgermanes are among the best radical acceptors yet identified, and this quality makes them superior reagent equivalents of the carbonyl radical acceptor synthon. Parent cyclizations in the 4-exo and 7-exo modes fail. Attempted 3-exo cyclization results in a 1,2-acyl shift, which can be conducted alone or in tandem with a subsequent cyclization to the rearranged acylgermane. The results provide a foundation for future synthetic applications of radical cyclizations to acylgermanes.

Chemistry of β-(Acyloxy)alkyl and β-(Phosphatoxy)alkyl Radicals and Related Species: Radical and Radical Ionic Migrations and Fragmentations of Carbon−Oxygen Bonds

“…No correlation was found with any of the σ • scales examined. The reaction coefficient of 2.1 versus σ p is very high for a radical reaction and strongly supports the notion that the (phosphatoxy)alkyl migration proceeds via transition states with substantial polar character, polarized in the way shown To gain an insight into the extent of polarization of the acyloxy shift, Beckwith and Duggan determined the rates of rearrangement of three p-substituted phenylpropyl butyrate derived radicals (438-440) and the related 441, generated from the corresponding bromides, by means of the stannane clock method ( Table 2, entries [16][17][18][19][20][21][22][23][24]. 164 At 75°C in benzene, a Hammett correlation with the substituent constant σ p + was obtained, giving a reaction coefficient of F ) -0.71.…”

“…Solvent effects on the rearrangement rate of the unsubstituted phenylbutanoate radical (438) were also examined. The results of experiments with six solvents that spanned a broad spectrum of polarities showed a clear dependence of the ester migration rate on solvent polarity ( Table 2, entries [16][17][18][19][20][21]. Correlation of the rates with the solvent polarity parameter E T 173 gave a slope of 0.024, again indicating a mild but discernible polarization in the transition state for the butyrate shift.…”

“…As this was not the case ( Table 5, entries 15 and 16), this pathway could be eliminated. Corroborating evidence is drawn from the rearrangements of the stereochemically labeled probes 224, 228, 230, and 233 for which the spectrum of products (Table 5, entries [17][18][19][20] was inconsistent with a phosphoranyl radical undergoing pseudorotation.…”

“…However, recent work suggests that this might not be the case. [13][14][15] It is only relatively recently that comparable intramolecular additions of alkyl radicals to acylgermanes [16][17][18][19] and acyl selenides, sulfides, 20 and sulfones 21,22 have been described. These reactions result in the expulsion of germyl, selenyl, thiyl, or sulfonyl radicals, respectively.…”

A Palladium/Light System Combined with Hanztsch Ester: Radical Vinylation of Alkyl Iodides with Vinyl Bromides

“…(2), Scheme 2]. [8,9] If key radicals speciesa re generated from alkyl halides, the leaving BrC has to be converted to an alkyl radical in order to sustain the radical chain. Currently,aseries of vinylation reactions by radical addition/fragmentation sequences are known, using vinyltins, [10] vinyl sulfides, [11] vinyl sulfones, [12] nitroalkenes, [13] vinylindiums, [14] vinylgalliums, [14b] vinyl chlorides, [15] and vinyl bromides.…”