A. E. Garst et al. / Tetrahedron Letters 54 (2013) 459–461
461
Next, the tandem reaction was assessed for scope and limitation
employing this simple two-step, one-pot procedure. Using propar-
gyl alcohol 2 as the model substrate, thiols of differing electronic
and structural configuration were screened for reactivity. The rear-
rangement reaction was followed by TLC and, after the propargyl
alcohol was consumed, 1.2 equiv of the thiol was added to the
reaction solution at room temperature. The reaction was readily
extended to a variety of electron-rich and electron-deficient thio-
phenol derivatives (Table 2, entries 1–6). Reaction time for the con-
jugate addition step ranged from 6–12 h for the thiophenol
derivatives. These tandem reactions yielded the b-sulfanyl ketones
in good to excellent yields (79–95%). In contrast, the additions of
benzyl mercaptan and dodecanethiol were very sluggish (37 h
and 22 h respectively) and led to the formation of 6g and 6h in
modest yields. Further optimization of the addition steps for these
thiols proved unsuccessful.
Next, we focused our attention on exploring the breadth of prop-
argyl alcohols that would undergo the rearrangement-conjugated
addition reaction sequence. For these reactions, 4-chlorothiophenol
was used as the model thiol. Propargyl alcohols bearing electron-
rich (Table 3, entries 1 and 2) and electron deficient (entries 3
and 4) aryl groups performed well under the standard reaction
conditions providing the corresponding b-sulfanyl ketones in
82–91% yield. The reaction times for the rearrangements were
relatively consistent and took 1.5–2 h. However, electronic config-
uration of the resultant enones had a noticeable effect on the rate
of thiol addition. The conjugate addition of 4-chlorothiophenol to
electron-rich substrates was considerably faster, 1.5–2 h for 7a
and 7b, as compared to 12–22 h for electron-deficient substrates
7c and 7d. Thiophenyl and indenyl substituted b-sulfanyl ketones
were obtained in good yield, 71% and 82% respectively, from the
rearrangement of propargyl alcohols 7e and 7f and subsequent con-
jugate additions. While these heteroaromatic substrates performed
well, the 3-furanyl propargyl alcohol 7g proved to be a challenging
substrate yielding 35% of the corresponding product. The low yield
is attributed to a moderately successful rearrangement. Analysis
of the rearrangement step of the reaction by TLC revealed a number
of decomposition products. Attempts to isolate and identify these
compounds were unsuccessful.
In summary, we have developed a practical method for a one-
pot tandem rearrangement and conjugate addition reaction. The
reaction allows for a range of b-sulfanyl ketones from propargyl
alcohols. Elaboration of these reactions are currently underway
in our laboratories and will be reported in due time.
Acknowledgments
We gratefully acknowledge the University of Richmond, the
Thomas F. and Kate Miller Jeffress Memorial Trust, and Research
Corporation for financial support.
Supplementary data
Supplementary data associated with this article can be found, in
11.047. These data include MOL files and InChiKeys of the most
important compounds described in this article.
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