C O M M U N I C A T I O N S
Table 2. S-N Addition of Sulfinamides to Arynesa
Scheme 2
Scheme 3
produce intermediate B. Intermediate B can then undergo intra-
molecular nucleophilic attack on the carbonyl carbon (or sulfinyl
group) to generate the unstable four-membered ring intermediate
C, which readily undergoes ring opening and protonation to afford
the final C-N insertion product.
To obtain further evidence to support our mechanism, we allowed
N-(2-iodophenyl)-N-phenyltrifluoroacetamide to react with n-BuLi
at a low temperature to generate intermediate B. Subsequent
rearrangement should afford the anticipated ketone. Indeed, we
obtained the desired ketone in a 45% yield (Scheme 3).
In summary, we have developed an efficient, mild, transition-
metal-free method for the intermolecular C-N addition of amides
and S-N addition of sulfinamides to arynes. Insertion products,
such as those produced herein, should prove useful in the prepara-
tion of Efavirenz derivatives11 and for the molecular recognition
of anions.12 A variety of functional groups are compatible with the
reaction conditions. Further studies on the reaction mechanism and
the scope of this process are in progress.
a Reaction conditions: 0.5 mmol of sulfinamide, 1.5 equiv of aryne
precursor, and 1.8 equiv of TBAF in 5.0 mL of THF at room temperature
for 30 min. b Isolated yield. c Employed with 1.0 equiv of 1a. d The reaction
is messy when CsF was employed as the base in MeCN.
(TBAF) as the fluoride source, instead of CsF, and THF as the
solvent, we were able to obtain the desired insertion product in an
80% yield in 30 min at room temperature (Table 2, entry 1).
The scope of this chemistry has been examined (Table 2). All
trifluoromethanesulfinamides work well with our standard aryne
precursors to afford the corresponding S-N insertion products in
high yields. Again, substrates with electron-donating or electron-
withdrawing groups afford high yields (entries 2 and 3). An
interesting thiazole derivative also afforded a high yield of aryne
insertion product (entry 4). Once again, these sulfinamides react
with the aryne precursors 1c and 1d to produce the corresponding
insertion products in good yields (entries 5 and 6). More interest-
ingly, the reaction of a substrate bearing both a trifluoroacetamide
and a trifluoromethanesulfinamide group afforded only the S-N
insertion product in a good yield, leaving the trifluoroacetamide
group untouched (entry 7). An N-alkyl sulfinamide has also been
shown to undergo this insertion chemistry, although the yield is a
little lower (entry 8).
As part of our mechanistic studies, we allowed N-phenylacet-
amide, N-phenyltrichloroacetamide, N-phenyltrichloromethane-
sulfinamide, and N-methyl-N-phenyltrifluoroacetamide to react with
the benzyne precursor 1a and CsF. No insertion products were
detected in any of these reactions, even when adding an additional
base, such as DBU. The presence of the CF3 moiety is clearly
critical to the success of this insertion chemistry, presumably
because this strong electron-withdrawing group increases the acidity
of the amide and also increases the electrophilicity of the carbonyl
carbon of the amide and the sulfinyl sulfur atom of the sulfinamide.
On the basis of our results, we propose the reaction mechanism
shown in Path A (Scheme 2), although we cannot rule out Path B.
Fluoride anion can both react with silylaryl triflate 1a to generate
benzyne and also act as a base to abstract the hydrogen on the
amide nitrogen to afford anion A, which can attack the benzyne to
Acknowledgment. We gratefully acknowledge the National
Science Foundation for support of this research.
Supporting Information Available: Detailed experimental pro-
cedure, and X-ray diffraction and characterization data for all previously
unknown products. This material is available free of charge via the
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