Journal of the American Chemical Society
Communication
(g) Zhou, X.; Xiao, T.; Iwama, Y.; Qin, Y. Angew. Chem., Int. Ed. 2012,
51, 4909−4912. (h) Chen, X.; Duan, S.; Tao, C.; Zhai, H.; Qiu, F. G.
Nat. Commun. 2015, 6, 7204.
(5) (a) Takayama, H.; Tominaga, Y.; Kitajima, M.; Aimi, N.; Sakai, S.-i.
J. Org. Chem. 1994, 59, 4381−4385. (b) Yamada, Y.; Kitajima, M.;
Kogure, N.; Wongseripipatana, S.; Takayama, H. Tetrahedron Lett. 2009,
50, 3341−3344.
(6) (a) Beyersbergen van Henegouwen, W. G.; Fieseler, R. M.; Rutjes,
F. P. J. T.; Hiemstra, H. Angew. Chem., Int. Ed. 1999, 38, 2214−2217.
(b) Beyersbergen van Henegouwen, W. G.; Fieseler, R. M.; Rutjes, F. P.
J. T.; Hiemstra, H. J. Org. Chem. 2000, 65, 8317−8325. (c) Shimokawa,
J.; Harada, T.; Yokoshima, S.; Fukuyama, T. J. Am. Chem. Soc. 2011, 133,
17634−17637. (d) Diethelm, S.; Carreira, E. M. J. Am. Chem. Soc. 2013,
135, 8500−8503. (e) Diethelm, S.; Carreira, E. M. J. Am. Chem. Soc.
2015, 137, 6084−6096.
(21) 1-Bromo-1-propyne is reported to be highly ignitable in pure
form. See: (a) Brandsma, L.; Verkruijsse, H. D. Synthesis 1990, 984−985.
(b) Nash, B. W.; Thomas, D. A.; Warburton, W. K.; Williams, T. D. J.
Chem. Soc. 1965, 2983−2988. As an alternative, we found it
straightforward to generate the reactant in a THF solution via
LHMDS-mediated elimination from 1,1-dibromopropene, and then
procedural details.
(22) (a) Nieto-Oberhuber, C.; Lop
́
ez, S.; Munoz, M. P.; Jimenez-
́
̃
Nunez, E.; Bunuel, E.; Cardenas, D. J.; Echavarren, A. M. Chem. - Eur. J.
́
́
̃
̃
2006, 12, 1694−1702. (b) Ferrer, C.; Raducan, M.; Nevado, C.;
Claverie, C. K.; Echavarren, A. M. Tetrahedron 2007, 63, 6306−6316.
(23) Platinacyclobutadiene formation between two alkynes appears to
be the main complication in using platinum catalysts. See, Konig, A.;
̈
Bette, M.; Bruhn, C.; Steinborn, D. Eur. J. Inorg. Chem. 2012, 5881−
5885.
(7) Kim, S. Y.; Park, Y.; Chung, Y. K. Angew. Chem., Int. Ed. 2010, 49,
415−418.
(8) (a) Newcomb, E. T.; Ferreira, E. M. Org. Lett. 2013, 15, 1772−
1775. (b) Stevenson, S. M.; Newcomb, E. T.; Ferreira, E. M. Chem.
Commun. 2014, 50, 5239−5241.
erosion in diastereoselectivity with this substrate (compared to
stereospecific process (E)-5 → 4) was curious, and attempts to increase
the dr above 3.2:1 were unfruitful. Studies are underway to elucidate the
origin of this phenomenon.
(25) Hintermann, L.; Labonne, A. Synthesis 2007, 1121−1150.
(26) Mahoney, W. S.; Brestensky, D. M.; Stryker, J. M. J. Am. Chem.
Soc. 1988, 110, 291−293.
(27) (a) Boivin, J.; Callier-Dublanchet, A.-C.; Quiclet-Sire, B.; Schiano,
A.-M.; Zard, S. Z. Tetrahedron 1995, 51, 6517−6528. (b) Zard, S. Z.
Chem. Soc. Rev. 2008, 37, 1603−1618.
(28) Kikugawa, Y.; Kawase, M. Chem. Lett. 1990, 581−582.
(29) Wasa, M.; Yu, J.-Q. J. Am. Chem. Soc. 2008, 130, 14058−14059.
(30) The diastereomeric mixture was purified at this stage.
(9) For select examples utilizing π-acid activation as key and/or late-
stage steps in target-oriented syntheses, see: (a) Kozak, J. A.; Dake, G. R.
Angew. Chem., Int. Ed. 2008, 47, 4221−4223. (b) Trost, B. M.; Dong, G.
Nature 2008, 456, 485−488. (c) Zhou, Q.; Chen, X.; Ma, D. Angew.
Chem., Int. Ed. 2010, 49, 3513−3516. (d) Molawi, K.; Delpont, N.;
Echavarren, A. M. Angew. Chem., Int. Ed. 2010, 49, 3517−3519.
(e) Michels, T. D.; Dowling, M. S.; Vanderwal, C. D. Angew. Chem., Int.
Ed. 2012, 51, 7572−7576. (f) Valot, G.; Regens, C. S.; O’Malley, D. P.;
Godineau, E.; Takikawa, H.; Furstner, A. Angew. Chem., Int. Ed. 2013, 52,
̈
9534−9538. (g) Lu, Z.; Li, Y.; Deng, J.; Li, A. Nat. Chem. 2013, 5, 679−
684. (h) Bian, Z.; Marvin, C. C.; Martin, S. F. J. Am. Chem. Soc. 2013,
135, 10886−10889. (i) Kong, K.; Enquist, J. A., Jr.; McCallum, M. E.;
Smith, G. M.; Matsumaru, T.; Menhaji-Klotz, E.; Wood, J. L. J. Am.
Chem. Soc. 2013, 135, 10890−10893.
(10) Zhao, L.; Lu, X.; Xu, W. J. Org. Chem. 2005, 70, 4059−4063.
(11) Konning, D.; Hiller, W.; Christmann, M. Org. Lett. 2012, 14,
̈
5258−5261.
(12) Geirsson, J. K. F.; Njardarson, J. T. Tetrahedron Lett. 1994, 35,
9071−9072.
(13) (a) Dugave, C.; Demange, L. Chem. Rev. 2003, 103, 2475−2532.
(b) Methot, J. L.; Roush, W. R. Adv. Synth. Catal. 2004, 346, 1035−
1050.
(14) This protocol allowed removal of the Pt catalyst prior to the Cope
rearrangement. The presence of the catalyst appeared to be detrimental
to the rearrangement of cyclopropane (E)-5.
(15) The relative stereochemistry of triene 13 is unconfirmed but is
drawn in the likely configuration, based on prior reports of 1,5-
homodienyl hydrogen migrations. See: (a) Pegg, G. G.; Meehan, G. V.
Aust. J. Chem. 1990, 43, 1009−1017. (b) Nakamura, E.; Kubota, K.;
Isaka, M. J. Org. Chem. 1992, 57, 5809−5810. (c) Loncharich, R. J.;
Houk, K. N. J. Am. Chem. Soc. 1988, 110, 2089−2092.
(16) In ref 7, only arene-substituted alkynes were investigated, where
this competitive migration would not be observed.
(17) There is some ambiguity in the mechanism of trans-to-cis
isomerization. See, Kruger, S.; Gaich, T. Beilstein J. Org. Chem. 2014, 10,
̈
163−193.
(18) (a) Using the ethyl ketone itself as the alkyne substituent was
problematic for the catalytic cycloisomerization for two main reasons:
(1) the alkyne electron deficiency rendered it more challenging for
catalytic activation, and (2) the alkyne polarization would induce C−C
bond formation at the undesired β position. (b) The n-propyl group was
chosen as the alkyne substituent originally, anticipating we could
convert it to an ethyl ketone via allylic oxidation at a later point.
(19) This aldehyde is synthesized in two steps from (Z)-but-2-ene-1,4-
diol and propargyl bromide in 70% yield following the procedure
(20) For a recent general review on the synthesis of 1,3-diynes, see, Shi,
W.; Lei, A. Tetrahedron Lett. 2014, 55, 2763−2772.
D
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX