Journal of the American Chemical Society
Article
(18) (a) Heppekausen, J.; Stade, R.; Goddard, R.; Furstner, A. J. Am.
A.; Liepins, V.; Poree
́
, F.-H.; Gilmour, R.; Laurich, D.; Beaufils, F.;
̈
Chem. Soc. 2010, 132, 11045−11057. (b) Persich, P.; Llaveria, J.;
Tamiya, M. Chem.Eur. J. 2009, 15, 3983−4010.
(40) (a) Smith, N. D.; Mancuso, J.; Lautens, M. Chem. Rev. 2000,
100, 3257−3282. (b) Trost, B. M.; Ball, Z. T. Synthesis 2005, 853−
887.
Lhermet, R.; de Haro, T.; Stade, R.; Kondoh, A.; Furstner, A. Chem.
̈
Eur. J. 2013, 19, 13047−13058. (c) Lhermet, R.; Furstner, A. Chem.
̈
Eur. J. 2014, 20, 13188−13193.
(19) Hoover, J. M.; Steves, J. E.; Stahl, S. S. Nat. Protoc. 2012, 7,
1161−1166.
(41) Nicolaou, K. C.; Jiang, X.; Lindsay-Scott, P. J.; Corbu, A.;
Yamashiro, S.; Bacconi, A.; Fowler, V. M. Angew. Chem., Int. Ed. 2011,
50, 1139−1144.
(20) Baker, R.; Castro, J. L. J. Chem. Soc., Perkin Trans. 1 1990, 47−
65.
(42) For other examples, see: (a) Neuhaus, C. M.; Liniger, M.;
Stieger, M.; Altmann, K.-H. Angew. Chem., Int. Ed. 2013, 52, 5866−
(21) (a) Abiko, A.; Liu, J.-F.; Masamune, S. J. Am. Chem. Soc. 1997,
119, 2586−2587. (b) Inoue, T.; Liu, J.-F.; Buske, D. C.; Abiko, A. J.
Org. Chem. 2002, 67, 5250−5256. (c) see also: Menche, D.; Hassfeld,
J.; Li, J.; Mayer, K.; Rudolph, S. J. Org. Chem. 2009, 74, 7220−7229.
(22) (a) Bonini, C.; Chiummiento, L.; Videtta, V. Synlett 2005,
3067−3070. (b) Bonini, C.; Chiummiento, L.; Videtta, V. Synlett 2006,
2079−2082.
5870. (b) Brewitz, L.; Llaveria, J.; Yada, A.; Furstner, A. Chem.Eur. J.
̈
2013, 19, 4532−4537.
(43) Model studies suggested that deiodination is as fast as or faster
than alkyne semireduction.
(44) Furstner, A.; Funel, J.-A.; Tremblay, M.; Bouchez, L. C.;
̈
Nevado, C.; Waser, M.; Ackerstaff, J.; Stimson, C. C. Chem. Commun.
2008, 2873−2875.
(23) (a) Micoine, K.; Furstner, A. J. Am. Chem. Soc. 2010, 132,
̈
(45) The individual components of this system had previously been
used separately, cf.: (a) Allred, G. D.; Liebeskind, L. S. J. Am. Chem.
Soc. 1996, 118, 2748−2749. (b) Srogl, J.; Allred, G. D.; Liebeskind, L.
S. J. Am. Chem. Soc. 1997, 119, 12376−12377.
14064−14066. (b) Micoine, K.; Persich, P.; Llaveria, J.; Lam, M.-H.;
Maderna, A.; Loganzo, F.; Furstner, A. Chem.Eur. J. 2013, 19,
̈
7370−7383.
(24) Northrup, A. B.; MacMillan, D. W. C. J. Am. Chem. Soc. 2002,
124, 6798−6799.
(46) These conditions have been widely used by us and others in
advanced syntheses; for pertinent applications, see refs 6, 7a, b, 8b, 39,
52b, 56 and the following: (a) Furstner, A.; Ackerstaff, J. Chem.
(25) Evans, D. A.; Ng, H. P.; Clark, J. S.; Rieger, D. L. Tetrahedron
1992, 48, 2127−2142.
̈
(26) Einhorn, J.; Einhorn, C.; Ratajczak, F.; Pierre, J.-L. J. Org. Chem.
1996, 61, 7452−7454.
Commun. 2008, 2870−2872. (b) Francais, A.; Leyva, A.; Etxebarria-
Jardi, G.; Ley, S. V. Org. Lett. 2010, 12, 340−343. (c) Paley, R. S.;
Berry, K. E.; Liu, J. M.; Sanan, T. T. J. Org. Chem. 2009, 74, 1611−
1620. (d) Paterson, I.; Kan, S. B. J.; Gibson, L. J. Org. Lett. 2010, 12,
3724−3727. (e) Paterson, I.; Gibson, L. J.; Kan, S. B. J. Org. Lett. 2010,
12, 5530−5533. (f) Otero, L.; Vaz, B.; Alvarez, R.; de Lera, A. R. Chem.
Commun. 2013, 49, 5043−5045. (g) Dominguez, M.; Alvarez, S.;
Alvarez, R.; de Lera, A. R. Tetrahedron 2012, 68, 1756−1761.
(27) Evans, D. A.; Chapman, K. T.; Carreira, E. M. J. Am. Chem. Soc.
1988, 110, 3560−3578.
(28) Although we were aware that MOM-cleavage can be
troublesome in the presence of acid-labile functionality, the choice
of this slim protecting group was dictated by the fact that neither a
TIPS nor a PMB-group could be efficiently attached to the C.7-OH at
this stage.
(h) Muller, S.; Mayer, T.; Sasse, F.; Maier, M. E. Org. Lett. 2011, 13,
̈
(29) Model studies showed that carbamate formation by
monoacylation of macrocyclic C7/C9-diol derivatives results in poor
selectivity and favors the undesired isomer, cf. ref 7; for a possible
solution, though not high yielding, see ref 6.
3940−3943. (i) Paley, R. S.; Laupheimer, M. C.; Erskine, N. A. K.;
Rablen, P. R.; Pike, R. D.; Jones, J. S. Org. Lett. 2011, 13, 58−61.
́
(j) Francais, A.; Leyva-Perez, A.; Etxebarria-Jardi, G.; Pena, J.; Ley, S.
V. Chem.Eur. J. 2011, 17, 329−343. (k) Renata, H.; Zhou, Q.;
(30) Kuwajima, I.; Doi, Y. Tetrahedron Lett. 1972, 12, 1163−1166.
(31) An alternative purely organocatalytic approach was studied but
found not to be competitive with this auxiliary-based tactics. In our
hands, the proline-catalyzed anti-aldol reaction of propionaldehyde
invariably gave a modest diastereoselectivity when performed on a >1
g scale (2:1 rather than 4:1, as described in ref 24), and all attempts at
converting the crude product into the corresponding methyl ester by a
triazolium-catalyzed aldehyde oxidation/esterification met with poor
results according to the procedure described in Brooks, E. M.; Chan,
A.; Phillips, E. M.; Scheidt, K. Tetrahedron 2009, 65, 3102−3109.
(32) Uno, B. E.; Gillis, E. P.; Burke, M. D. Tetrahedron 2009, 65,
3130−3138.
Baran, P. S. Science 2013, 339, 59−63.
(47) Boland, W.; Schroer, N.; Sieler, C.; Feigel, M. Helv. Chim. Acta
1987, 70, 1025−1040.
(48) For other instructive cases, see: (a) Hickmann, V.; Kondoh, A.;
Gabor, B.; Alcarazo, M.; Furstner, A. J. Am. Chem. Soc. 2011, 133,
̈
13471−13480. (b) Chaladaj, W.; Corbet, M.; Furstner, A. Angew.
̈
Chem., Int. Ed. 2012, 51, 6929−6933. (c) Hoffmeister, L.; Persich, P.;
Furstner, A. Chem.Eur. J. 2014, 20, 4396−4402. (d) Willwacher, J.;
̈
Furstner, A. Angew. Chem., Int. Ed. 2014, 53, 4217−4221. (e) Guy, A.;
̈
Oger, C.; Heppekausen, J.; Signorini, C.; De Felice, C.; Furstner, A.;
̈
Durand, T.; Galano, J.-M. Chem.Eur. J. 2014, 20, 6374−6380.
(49) Furstner, A. Science 2013, 341, 1229713.
̈
(33) Wu, T. R.; Shen, L.; Chong, J. M. Org. Lett. 2004, 6, 2701−
2704.
(50) 11/CH2Cl2 is known to be incompatible with free alcohols, see
ref 16.
(34) (a) Lou, S.; Moquist, P. N.; Schaus, S. E. J. Am. Chem. Soc. 2006,
128, 12660−12661. (b) Barnett, D. S.; Moquist, P. N.; Schaus, S. E.
Angew. Chem., Int. Ed. 2009, 48, 8679−8682.
(35) (a) Barnett, D. S.; Schaus, S. E. Org. Lett. 2011, 13, 4020−4023.
(b) For a review on asymmetric ketone propargylation, see:
Wisniewska, H. M.; Jarvo, E. R. J. Org. Chem. 2013, 78, 11629−11639.
(36) However, the reaction may not be general because attempted
asymmetric propargylations of ethyl or tert-butyl 3-oxo-butanoate led
to complex mixtures.
(51) Schrock, R. R. Chem. Rev. 2002, 102, 145−179.
(52) (a) Gebauer, K.; Furstner, A. Angew. Chem., Int. Ed. 2014, 53,
̈
6393−6396. (b) Valot, G.; Regens, C. S.; O’Malley, D. P.; Godineau,
E.; Takikawa, H.; Furstner, A. Angew. Chem., Int. Ed. 2013, 52, 9534−
̈
9538.
̌
́
(53) Kocovsky, P. Tetrahedron Lett. 1986, 27, 5521−5524.
(54) (a) Guindon, Y.; Morris, H. E.; Yoakim, C. Tetrahedron Lett.
1983, 24, 3969−3972. (b) Guidon, Y.; Yoakim, C.; Morton, H. E. J.
Org. Chem. 1984, 49, 3912−3920.
(37) Grayson, M. N.; Goodman, J. M. J. Org. Chem. 2013, 78, 8796−
8801.
(55) (a) Wilson, R. M.; Danishefsky, S. J. J. Org. Chem. 2006, 71,
8329−8351. (b) Wilson, R. M.; Danishefsky, S. J. Angew. Chem., Int.
Ed. 2010, 49, 6032−6056. (c) Szpilman, A. M.; Carreira, E. M. Angew.
(38) Farina, V.; Krishnamurthy, V.; Scott, W. J. Org. React. 1997, 50,
1−652.
Chem., Int. Ed. 2010, 49, 9592−9628. (d) Furstner, A. Isr. J. Chem.
̈
(39) For pertinent examples, see: (a) Gagnepain, J.; Moulin, E.;
Furstner, A. Chem.Eur. J. 2011, 17, 6964−6972. (b) Furstner, A.;
2011, 51, 329−345. (e) Wach, J.-Y.; Gademann, K. Synlett 2012, 23,
163−170.
̈
̈
Bouchez, L. C.; Funel, J.-A.; Liepins, V.; Poree
́
, F.-H.; Gilmour, R.;
(56) This conformational detail is reminiscent of the solution
structure of iejimalide B, in which an E,E-configured 1,3-diene also
forms a “wall” perpendicular to the plane of the macrocycle of this
Beaufils, F.; Laurich, D.; Tamiya, M. Angew. Chem., Int. Ed. 2007, 46,
9265−9270. (c) Furstner, A.; Bouchez, L. C.; Morency, L.; Funel, J.-
̈
J
dx.doi.org/10.1021/ja508846g | J. Am. Chem. Soc. XXXX, XXX, XXX−XXX