Organic Letters
Letter
Scheme 1. Gold-Catalyzed Dehydrative Cyclization of Diol 3g
in the Presence of Iodine
AUTHOR INFORMATION
Corresponding Authors
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Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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Table 4. Gold-Catalyzed Dehydrative Spirocyclization of Triols 6
Financial support for our programs in green chemistry provided
by the NIH (GM 86485) to B.H.L. is warmly acknowledged with
thanks.
DEDICATION
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Dedicated with the utmost respect, admiration, and appreciation
to the memory of Professor Harry H. Wasserman, who passed
away on December 29, 2013.
REFERENCES
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a
entry
6
R1
R2
n
[Au]
time (h) 7/yield (%)
(1) (a) Lipshutz, B. H.; Ghorai, S. Aldrichimica Acta 2008, 41, 59−72.
(b) Lipshutz, B. H.; Ghorai, S. Aldrichimica Acta 2012, 45, 3−16.
(c) Lipshutz, B. H.; Isley, N. A.; Fennewald, J. C.; Slack, E. D. Angew.
Chem., Int. Ed. 2013, 52, 10952−10958.
(2) (a) Lipshutz, B. H.; Aguinaldo, G. T.; Ghorai, S.; Voigtritter, K. Org.
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1
2
3
4
5
6a
6b
6b
6b
6c
Ph
Ph
Ph
Ph
H
0
0
0
0
1
Ph3PAuCl
Ph3PAuCl
5
7a (89)
7b (11)
7b (22)
7b (46)
Me
Me
Me
Me
4
b
c
B
4
d
C
4
e
H
b
Ph3PAuCl
12
7c (64)
a
c
d
Isolated yield. B = [c-Hex2(o-biphenyl)]PAuCl. 40 °C. C = [t-Bu2-
e
(o-biphenyl)]PAuCl. 19% reisolated starting material.
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transformation, in the presence of activated molecular sieves
for scavenging water.13 Triol 6a was smoothly cyclized with
Ph3PAuCl/AgOTf in water containing 2 wt % TPGS-750-M at
room temperature over 5 h to the corresponding spirocycle 7a
(89% yield; entry 1). Under the same conditions, increased steric
hindrance at the 1- and 3-positions dramatically slowed the
conversion (triol 6b; entry 2). An increased rate of protodeaura-
tion after the initial cyclization led to formation of a complex
mixture containing unsaturated monocyclization products13a
together with the desired spirocycle 7b. With a cationic gold(I)
catalyst formed from B and AgOTf the yield of 7b could be
doubled (entry 3), but it was only after the use of precatalyst
C/AgOTf that a moderate yield of product 7b could be isolated
(46%; entry 4). The related triol 6c bearing the same steric
hindrance at the 1- and 3-positions, but with a longer carbon chain
(albeitwithoutphenyl substituents), could becyclized in64% yield
to the corresponding spirocycle 7c upon heating to 40 °C for 12 h.
In summary, acetylenic vicinal diols and amino alcohols can
be cyclodehydrated to the corresponding furans and pyrroles,
respectively, using nanoparticle technology in water. Nano-
micelles composed of the designer surfactant TPGS-750-M,
which is an item of commerce,14 enable these gold-catalyzed re-
actions to take place at ambient temperatures and in high isolated
yields. Appropriately substituted alkynes containing three hy-
droxyl residues can be converted to spirocyclic products in
the presence of a Au(I) catalyst. Further work on developing an
enantioselective version of this route to spirocycles is currently
under study.
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(9) Klumphu, P.; Lipshutz, B. H. J. Org. Chem., in press, DOI:
jo401744b.
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2011, 50, 7820−7823.
(12) (a) Gockel, B.; Krause, N. Eur. J. Org. Chem. 2010, 311−316.
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(14) Aldrich catalog numbers 733857 and 763918.
ASSOCIATED CONTENT
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Experimental procedures and data for all new compounds. This
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