Abstract
This account provides an overview, in varying depth, of our research into diverse aspects of acetylene chemistry over the last three decades. Initial studies with acetylenic natural products (Wyerone, Crepenynic Acid) were followed several years later with synthetically oriented projects. These involved enediyne mimics of natural products (Taxamycins) and unusual selenium dioxide oxidations of α-alkynyl ethers. Helical acetylenic cyclophanes (Revolvenynes) were synthesized by sequential palladium- and copper-mediated reactions, which set the precedent for later research. Related cyclophanes as potential intermediates for buckminsterfullerene (C60) are discussed. Helical carbocyclic liquid crystalline and heterocyclic (copper-free and complexed) cyclophanes were also prepared. A very strained 153.5° triple bond was discovered which reacted with cyclohexadiene to form the bicyclic adduct in situ and extruded ethylene to generate a new cyclophane with an annulated benzene ring attached. In situ desilylation-dimerization sequences are described and a table is presented for guidance to predict the preferred product from competing intra- and intermolecular copper-mediated coupling pathways. The synthetic details for two different helical, π-stacked C60 cyclophane families with para and meta bonded caps and different structural motifs are presented (Scheme
[13 14 1
1 Acetylene Natural Products (Wyerone, Crepenynic Acid)
2 Enediynes (Taxamycins)
3 Acetylenic Cyclophanes
3.1 Revolvenynes
3.2 Enediynes for C60?
3.3 Carbocycles
3.4 Heterocycles
3.5 C60 Carbocycles
3.6 Termini Separation
4 Allenophanes
5 π-Conjugated Boranes
6 Propargyl Alcohols (Magnesium-Mediated Carbometallations)
7 Buckminsterfullerene (Revisited)
8 Conclusion
Key words
enediyne - acetylene - palladium - copper - cyclophanes - propargyl alcohols - magnesium - C60
References 1 I have taken Peter at his word and this account is not a comprehensive review but a personal journey through the forest of organic chemistry. I apologize for only passing credit to the chemical literature and the discoveries of others that made our work possible.
2a Fallis AG.
Can. J. Chem.
1984,
62:
183
2b Fallis AG.
Lu YF.
Adv. Cycloaddit.
1993,
3:
1
2c Fallis AG.
Pure Appl. Chem.
1997,
69:
495
2d Fallis AG.
Acc. Chem. Res.
1999,
32:
464
2e Fallis AG.
Brinza I.
Tetrahedron
1997,
53:
17543
2f Fallis AG.
Forgione P.
Tetrahedron
2001,
57:
5899
3 Dewick PM.
Medicinal Natural Products. A Biosynthetic Approach
2nd ed.:
J. Wiley and Sons;
Chichester:
2002.
p.48-49
4 I later learned that his wife apparently preferred the bustle and bright lights of London to the pastoral scholarly life of Cambridge!
5 Fawcett CH.
Spencer DM.
Wain RL.
Fallis AG.
Jones ERH.
Lequan M.
Page CB.
Thaller V.
Shubrook DC.
Whitham PM.
J. Chem. Soc. C
1968,
2455
6a Fallis AG.
Jones ERH.
Thaller V.
J. Chem. Soc., Chem. Commun.
1969,
924
6b Fallis AG.
Hearn MTW.
Jones ERH.
Thaller V.
Turner JL.
J. Chem. Soc., Perkin Trans. 1
1973,
743
7 Birkenbach L.
Gonbeau J.
Chem Ber.
1934,
67:
1420
8 Cadiot P.
Chodkiewicz W. In Chemistry of Acetylenes
Viehe HJ.
M. Dekker;
New York, NY:
1969.
p.616
9 Reed DW.
Polichuk DR.
Buist PH.
Ambrose SJ.
Sasata RJ.
Savile CK.
Ross ARS.
Covello PS.
J. Am. Chem. Soc.
2003,
125:
10635
10a Lu YF.
Fallis AG.
Tetrahedron Lett.
1993,
34:
3367
10b Lu Y.-F.
Fallis AG.
Can. J. Chem.
1995,
73:
2239
11 Shea KJ.
Gilman JW.
Haffner CD.
Dougherty TK.
J. Am. Chem. Soc.
1986,
108:
4953
12a Nicolaou KC.
Claiborne CF.
Nantermet PG.
Couladouros EA.
Sorensen EJ.
J. Am. Chem. Soc.
1994,
116:
1591
12b Morihira K.
Nishimori T.
Kusama H.
Horiguchi Y.
Kuwajima I.
Tsuruo T.
Bioorg. Med. Chem. Lett.
1998,
8:
2973
12c Smil DV.
Laurent A.
Fallis AG.
Tetrahedron Lett.
2003,
44:
5129
13a Lu Y.-F.
Harwig CW.
Fallis AG.
J. Org. Chem.
1993,
58:
4202
13b Lu Y.-F.
Harwig CW.
Fallis AG.
Can. J. Chem.
1995,
73:
2253
14 Harwig CW.
Py S.
Fallis AG.
J. Org. Chem.
1997,
62:
7902
15 Crevisy C.
Beau J.-M.
Tetrahedron Lett.
1991,
32:
3171
16a Okude Y.
Hirano S.
Hiyama T.
Nozaki H.
J. Am. Chem. Soc.
1977,
99:
3175
16b Jin H.
Uenishi J.
Christ WJ.
Kishi Y.
J. Am. Chem. Soc.
1987,
109:
5644
17 Didier E.
Fouque F.
Taillepied I.
Commerçon A.
Tetrahedron Lett.
1994,
35:
2349
18 Py S.
Harwig CW.
Banerjee S.
Brown DL.
Fallis AG.
Tetrahedron Lett.
1998,
39:
6139
19 Comanita BM.
Heuft MA.
Rietveld T.
Fallis AG.
Isr. J. Chem.
2000,
40:
241
20 Romero MA.
Fallis AG.
Tetrahedron Lett.
1994,
35:
4711
21 Canada has a strategic grant program to support research in collaboration with an industrial partner, provided there is applied potential that will benefit society.
22 Rubin Y.
Parker TC.
Khan SI.
Holliman CL.
McElvany SW.
J. Am. Chem. Soc.
1996,
118:
5308
23 Collins SK.
Yap GPA.
Fallis AG.
Angew. Chem. Int. Ed.
2000,
39:
385
24 Collins SK.
Yap GPA.
Fallis AG.
Org. Lett.
2000,
2:
3185
25a Nuckolls C.
Katz TJ.
J. Am. Chem. Soc.
1998,
120:
9541
25b Nuckolls C.
Katz TJ.
Katz G.
Collings PJ.
Castellanos L.
J. Am. Chem. Soc.
1999,
121:
79
26 Collins SK.
Yapp GP.
Fallis AG.
Org. Lett.
2002,
4:
11
27a Ikegashira K.
Nishihara Y.
Hirabayashi K.
Mori A.
Hiyama T.
Chem. Commun.
1997,
1039
27b Haley MM.
Bell ML.
Brand SC.
Kimball DB.
Pak JJ.
Wan WB.
Tetrahedron Lett.
1997,
38:
7483
27c Nishihara Y.
Ikegashira K.
Mori A.
Hiyama T.
Tetrahedron Lett.
1998,
39:
4075
28 Heuft MA.
Collins SK.
Yap GPA.
Fallis AG.
Org. Lett.
2001,
3:
2883
29 Joshi HS.
Jamshidi R.
Tor Y.
Angew. Chem. Int. Ed.
1999,
38:
2722
30 Shvo Y.
Taylor EC.
Mislow K.
Raban H.
J. Am. Chem. Soc.
1967,
89:
4910
31 Heuft MA.
Fallis G.
Angew. Chem. Int. Ed.
2002,
41:
4520
32a Wu Z.
Lee S.
Moore JS.
J. Am. Chem. Soc.
1992,
114:
8730
32b Yu Z.
Kahr M.
Walker KL.
Wilkins CL.
Moore JS.
J. Am. Chem. Soc.
1994,
116:
4537
32c Moore JS.
Acc. Chem. Res.
1997,
30:
402
32d Boese R.
Matzger AJ.
Vollhardt KPC.
J. Am. Chem. Soc.
1997,
119:
2052
32e Haley MM.
Bell ML.
English JJ.
Johnson CA.
Weakley TJR.
J. Am. Chem. Soc.
1997,
119:
2956
32f Haley MM.
Brand SC.
Pak JJ.
Angew. Chem., Int. Ed. Engl.
1997,
36:
836
32g Wan WB.
Kimball DB.
Haley MM.
Tetrahedron Lett.
1998,
39:
6795
32h Matzger AJ.
Vollhardt KPC.
Tetrahedron Lett.
1998,
39:
6791
32i Wan WB.
Kimball DB.
Haley MM.
Tetrahedron Lett.
1998,
39:
6795
32j Matzger AJ.
Vollhardt KPC.
Tetrahedron Lett.
1998,
39:
6791
32k Bunz UHF.
Rubin Y.
Tobe Y.
Chem. Soc. Rev.
1999,
28:
107
32l Pak JJ.
Weakley TJR.
Haley MM.
J. Am. Chem. Soc.
1999,
121:
8182
32m Pak JJ.
Weakley TJR.
Haley MM.
J. Am. Chem. Soc.
1999,
121:
8182
32n Kehoe JM.
Kiley JH.
English JJ.
Johnson CA.
Peterson RC.
Haley MM.
Org. Lett.
2000,
2:
969
32o Wan WB.
Haley MM.
J. Org. Chem.
2001,
66:
3893
32p Boydston AJ.
Haley MM.
Williams RV.
Armantrout JR.
J. Org. Chem.
2002,
67:
8812
32q Bangcuyo CG.
Smith MD.
Bunz UHF.
Synlett
2004,
169
33 Heuft MA.
Collins SK.
Fallis AG.
Org. Lett.
2003,
5:
1911
34 Ohira S.
Synth. Commun.
1989,
19:
561
35 Tsuzuki S.
Honda K.
Uchimaru T.
Mikami M.
Tanaba K.
J. Am. Chem. Soc.
2000,
124:
104
36 Universal Force Field (UFF) calculations were obtained using the Cerius2 -Dmol3 molecular modeling suite from Molecular Simulations Inc. San Diego, 1999. We thank S. Drouin and D. Fogg (University of Ottawa) for assistance.
37 Heuft MA.
Ph.D. Thesis
University of Ottawa;
Ontario:
2003.
38 Thorand S.
Vogtle F.
Krause K.
Angew. Chem. Int. Ed.
1999,
38:
3721
39 Clay, M. D. unpublished results.
40a Yamaguchi S.
Akiyama S.
Tamao K.
J. Am. Chem. Soc.
2000,
122:
6335
40b Yamaguchi S.
Shiraska T.
Tamo K.
Org. Lett.
2000,
2:
4129
41 Tiffen JL.
M.Sc. Thesis
University of Ottawa;
Ontario:
2002.
42a Eisch JJ. Merkley JH.
J. Organomet. Chem.
1969,
20:
27
42b Richey HG.
von Rein FW.
J. Organomet. Chem.
1969,
20:
32
42c Jousseaume B.
Duboudin JG.
J. Organomet. Chem.
1975,
C1
43a Wong T.
Tjepkema MW.
Audrain H.
Wilson PD.
Fallis AG.
Tetrahedron Lett.
1996,
37:
755
43b Forgione P.
Fallis AG.
Tetrahedron Lett.
2000,
41:
11
43c Forgione P.
Wilson PD.
Fallis AG.
Tetrahedron Lett.
2000,
41:
17
43d Forgione P.
Wilson PD.
Yap GPA.
Fallis AG.
Synthesis
2000,
921
43e Villava-Servin NP.
Laurent A.
Fallis AG.
Synlett
2003,
1261
44 Tessier PJ.
Penwell AJ.
Souza FES.
Fallis AG.
Org. Lett.
2003,
5:
2989
45 Tessier PJ.
M.Sc. Thesis
University of Ottawa;
Ontario:
2003.
46 Matsuura A.
Komatsu K.
J. Am. Chem. Soc.
2001,
123:
1768
47a Lei A.
Srivastava M.
Zhang X.
J. Org. Chem.
2002,
67:
1969
47b Marsden JA.
Miller JJ.
Haley MM.
Angew. Chem. Int. Ed.
2004,
43:
1694
48 After submission of this manuscript for review, a current group member volunteered to examine this idea. The Grignard 134 could not be generated from 81 with magnesium turnings, but with Reike® magnesium it acted as a base and the chloride was eliminated to generate the triple bond (Scheme
[13
