Radical Chain Reaction of Benzenethiol with Pentynylthiol Esters: Production of Aldehydes under Stannane/Silane-Free Conditions

Abstract

The radical chain reaction of benzenethiol with accessible 4-pentynylthiol esters provides a new stannane/silane-free protocol for the production of aromatic and aliphatic aldehydes. The procedure is especially useful for the aryl and primary aldehydes, even in the presence of substituents highly sensitive to reductive conditions, and is also of some utility for the vinylic and secondary ones. The protocol is instead not applicable to the tertiary aldehydes, owing to preferential alkane-forming decarbonylation, although the tertiary ones derived from bridgehead precursors can still be usefully produced.

Key words

acyl radicals - reduction - aldehydes - benzenethiol - thiol esters

References

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13

General Procedure for the Preparation of Thiol Esters 1: To a stirred solution of 10 mmol of the appropriate acyl chloride, directly available or prepared by treatment of commercial or already known acid with SOCl₂, and DMAP (1.6 g, 13 mmol) in CH₂Cl₂ (20 mL) was slowly added, at r.t. and under a stream of nitrogen, a solution of 4-pentyne-1-thiol (1 g, 10 mmol) [7] in CH₂Cl₂ (100 mL). The resulting mixture was stirred at r.t. for an additional 1-2 h, until disappearance of the thiol reagent (TLC), then treated with Et₂O (100 mL) and eventually filtered. The organic filtrate was concentrated and the residue subjected to column chromatography. The title compounds were obtained in 60-80% yields and were characterized on the basis of ¹H NMR and ¹³C NMR spectral data. Illustrative data for S-(4-pentynyl) 4-chlorobenzenecarbothiate(1b): ¹H NMR (300 MHz, CDCl₃): δ = 1.91 (m, 2 H, CH₂), 2.01 (t, 1 H, alkynylic CH, J = 2.61 Hz), 2.34 (dt, 2 H, CH_2, J ₁ = 2.61 Hz, J ₂ = 6.95 Hz), 3.20 (t, 2 H, CH₂, J = 6.95 Hz), 7.43 (m, 2 H, aromatic CH), 7.91 (m, 2 H, aromatic CH). ¹³C NMR (75 MHz, CDCl₃): δ = 17.82 (CH₂), 28.13 (CH₂), 28.44 (CH₂), 69.50 (CH), 83.13 (C), 128.71 (CH), 129.07 (CH), 135.51 (C), 139.91 (C), 190.64 (CO).

14

General Procedure for the Reactions of Thiol Esters 1 with Benzenethiol: A benzene (20 mL) solution of PhSH (2.2 mmol) and AIBN (0.4 mmol) was added by a syringe pump over ca. 3 h to a refluxing solution of the appropriate thiol ester (2 mmol) in degassed benzene (30 mL) under a nitrogen atmosphere. The resultant mixture was refluxed for an additional 2-3 h until the virtual disappearance of the starting substrate (TLC). After cooling to r.t., the solvent was removed in vacuo and the residue subjected to chromatographic separation on silica gel by progressive elution with light petroleum/Et₂O mixtures. The aldehydes 4a-c,f-h,k, as well as the alkanes 5-7, were commercial products. The known aldehydes 4d, [15a] 4e, [15b] 4j, [15c] 4l, [15d] and 4m [15e] were characterized by ¹H NMR and ¹³C NMR spectral data. The vinyl sulfides 3a-h,j-m were generally obtained as an inseparable mixtures of the E- and Z-isomer.

17

Previous attempts to obtain 2-hexenal by photochemical homolysis of (S)-2-naphthyl-2-hexenethioate resulted in extensive formation of reduced hexanal: see ref. [11]

18

When the same azidoalkanoyl radical was generated by the method of Crich, in the presence of Bu₃SnH, the production of aldehyde 4i was totally suppressed in favor of decarbonylated and lactam product: see ref. [2]

19

1-Adamantanecarbonyl chloride is totally converted into adamantane upon radical reaction with (TMS)₃SiH at 80 °C: see ref. [9a]

20

The amount of the resulting vinyl sulfide adduct 3 was not significantly diminished when an alkanethiol such as methyl thioglycolate was used in place of benzenethiol.