Page 5 of 7
Journal of the American Chemical Society
(c) Aono, M.; Hyodo, C.; Terao, Y.; Achiwa, K. New Method for Genera-
Notes
tion of Thiocarbonyl Ylides from Bis(trimethylsilylmethyl)sulfoxides and
Their Application to Cycloadditions. Heterocycles 1995, 40, 249–260; (d)
Ishida, H.; Ohno, M. The first 1,3-dipolar cycloaddition reaction of
[60]fullerene with thiocarbonyl ylide. Tetrahedron Lett. 1999, 40, 1543–
1546.
1
2
3
4
5
6
7
8
The authors declare no competing financial interests.
ACKNOWLEDGMENT
This work was supported by the Austrian Science Fund FWF
(P31023-NBL to T.M.), the Center for Molecular Biosciences
CMBI and the Tyrolean Science Fund TWF (UNI-0404/2340 to
F.-L.H.). We are grateful to Prof. Dirk Trauner (New York Uni-
versity) for providing unpublished data and helpful discussions.
Furthermore, we thank Dr. Gabriele Prina Cerai and Robin Poller
(University of Innsbruck) for assistance during the preparation of
this manuscript.
(9)
For related methods to generate thiocarbonyl ylides, see: (a)
Vedejs, E.; Martinez, G. R. Methylides from trimethylsilylmethyl-
sulfonium, -ammonium, -immonium, and -phosphonium salts. J. Am.
Chem. Soc. 1979, 101, 6452–6454; (b) Matsuyama, Y.; Sakurai, H.
Chloromethyl trimethylsilylmethyl sulphide as a parent thiocarbonyl ylide
synthon. A simple synthesis of dihydro- and tetrahydro-thiophenes. J
Chem. Soc. Chem. Commun. 1986, 1073–1074; (c) Cameron, T. B.;
Pinnick, H. W. Flash vacuum pyrolysis of 1,3-oxathiolan-5-ones. J. Am.
Chem. Soc. 1980, 102, 744–747; (d) Huisgen, R.; Mloston, G. Adaman-
tanethione and diazomethane; A re-examination. Tetrahedron Lett. 1985,
26, 1049–1052.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
REFERENCES
(10)
Speck, K.; Magauer, T. Evolution of a Polyene Cyclization
(1)
(a) Long, R.; Huang, J.; Gong, J.; Yang, Z. Direct construction
Cascade for the Total Synthesis of (−)-Cyclosmenospongine. Chem. Eur.
J. 2017, 23, 1157–1165.
(11)
Organic Reactions in Fluids – a New Theoretical Perspective. Angew.
Chem. Int. Ed. 2017, 56, 11126–11142.
(12)
mations in Natural Product Synthesis. Synthesis 2014, 46, 1279–1296.
(13) (a) Winter, N.; Trauner, D. Thiocarbonyl Ylide Chemistry En-
ables a Concise Synthesis of (±)-Hippolachnin A. J. Am. Chem. Soc. 2017,
139, 11706−11709; (b) Winter, N.; Rupcic, Z.; Stadler, M.; Trauner, D.
Synthesis and biological evaluation of (±)-hippolachnin and analogs. J.
Antibiot. 2019, 72, 375–383; (c) Winter, N.; Trauner, D. Personal Com-
munication.
of vicinal all-carbon quaternary stereocenters in natural product synthesis.
Nat. Prod. Rep., 2015, 32, 1584–1601; (b) Lin, J.; Song, R.-J.; Hu, M.; Li,
J.-H. Recent Advances in the Intermolecular Oxidative Difunctionaliza-
tion of Alkenes. Chem. Rec. 2019, 19, 440–451.
Chen, B.; Hoffmann, R.; Cammi, R. The Effect of Pressure on
(2)
(a) Peterson, E. A.; Overman, L. E. Contiguous stereogenic
Hugelshofer, C. L.; Magauer, T. High-Pressure Transfor-
quaternary carbons: A daunting challenge in natural products synthesis
Proc. Natl. Acad. Sci. USA 2004, 101, 11943–11948; (b) Quasdorf, K. W.;
Overman, L. E. Catalytic enantioselective synthesis of quaternary carbon
stereocentres. Nature 2014, 516, 181–191.
(3)
For selected examples of transition-metal catalyzed dicarbo-
functionalization protocols, see: (a) García-Domínguez, A.; Li, Z.; Neva-
do, C. Nickel-Catalyzed Reductive Dicarbofunctionalization of Alkenes J.
Am. Chem. Soc. 2017, 139, 6835−6838; (b) Bao, X.; Yokoe, T.; Ha, T.
M.; Wang, Q.; Zhu, J. Copper-catalyzed methylative difunctionalization of
alkenes. Nat. Commun. 2018, 9, 3725; (c) Lin, J.-S.; Li, T.-T.; Liu, J.-R.;
Jiao, G.-Y.; Gu, Q.-S.; Cheng, J.-T.; Guo, Y.-L.; Hong, X.; Liu; X.-Y.
Cu/Chiral Phosphoric Acid-Catalyzed Asymmetric Three-Component
Radical-Initiated 1,2-Dicarbofunctionalization of Alkenes. J. Am. Chem.
Soc. 2019, 141, 1074−1083; (d) Hethcox; J. C.; Shockley, S. E.; Stoltz; B.
M. Enantioselective Synthesis of Vicinal All-Carbon Quaternary Centers
via Iridium-Catalyzed Allylic Alkylation. Angew. Chem. Int. Ed. 2018, 57,
8664–8667; (e) Trost; B. M.; Osipov; M. Palladium-Catalyzed Asymmet-
ric Construction of Vicinal All-Carbon Quaternary Stereocenters and its
Application to the Synthesis of Cyclotryptamine Alkaloids. Angew. Chem.
Int. Ed. 2013, 52, 9176–9181; (f) White, D. R.; Hinds, E. M.; Bornowski,
E. C.; Wolfe, J. P. Pd-Catalyzed Alkene Difunctionalization Reactions of
Malonate Nucleophiles: Synthesis of Substituted Cyclopentanes via
Alkene Aryl-Alkylation and Akenyl-Alkylation. Org. Lett. 2019, 21,
3813−3816.
(14)
(a) Hauptmann, H.; Walter, W. F. The Action of Raney Nickel
on Organic Sulfur Compounds. Chem. Rev. 1962, 62, 347−404; (b) Dan-
ishefsky, S.; Tsuzuki, K. Simple, efficient total synthesis of cantharidin
via a high-pressure Diels-Alder reaction. J. Am. Chem. Soc. 1980, 102,
6893–6894; (c) Smith, M. W.; Snyder, S. A. A Concise Total Synthesis of
(+)-Scholarisine A Empowered by a Unique C–H Arylation. J. Am. Chem.
Soc. 2013, 135, 12964−12967; (d) Rentner, J.; Kljajic, M.; Offner, L.;
Breinbauer, R. Recent advances and applications of reductive desulfuriza-
tion in organic synthesis. Tetrahedron 2014, 70, 8983−9027; (e) Lin, R.;
Cao, L.; West, F. G. Medium-Sized Cyclic Ethers via Stevens [1,2]-Shift
of Mixed Monothioacetal-Derived Sulfonium Ylides: Application to
Formal Synthesis of (+)-Laurencin. Org. Lett. 2017, 19, 552−555.
(15)
Sulfoxide 1a undergoes sila-Pummerer rearrangement with a
half-life time of approximate 10 h at 23 °C (see Supporting Information
for details). The conversion for low yielding substrates can be increased
by further addition of 1a. For related sila-Pummerer rearrangements, see:
(a) Ye, X.-S.; Wong, H. N. C. Synthetic Applications of 3,4-
Bis(trimethylsilyl)thiophene:ꢀ Unsymmetrically 3,4-Disubstituted Thio-
phenes and 3,4-Didehydrothiophene. J. Org. Chem. 1997, 62, 1940–1954;
(b) Magyarosy, A.; Mohareb, R. M.; Ho, J. Z. Cycloaddition approach to
the curing of polyimides via precursor containing thiophene-S,S-dioxide.
Heteroatom Chem. 2006, 17, 648–652; (c) Li, D. B.; Rogers-Evans, M.;
Carreira, E. M. Construction of Multifunctional Modules for Drug Dis-
covery: Synthesis of Novel Thia/Oxa-Azaspiro[3.4]octanes. Org. Lett.
2013, 15, 4766–4769.
(4)
(a) Fleming, I. in Pericyclic Reactions, Oxford Univ. Press:
Oxford, 2015; (b) Chen, T.-G.; Barton, L. M.; Lin, Y.; Tsien, J.; Kossler,
D.; Bastida, I.; Asai, S.; Bi, C.; Chen, J. S.; Shan, M.; Fang, H.; Fang, F.
G.; Choi, H.-W., Hawkins, L.; Baran, P. S. Building C(sp3)-rich complexi-
ty by combining cycloaddition and C–C cross-coupling reactions. Nature
2018, 560, 350–354.
(5) (a) Mloston, G.; Heimgartner, H. in Synthetic Applications of 1,3-
Dipolar Cycloaddition Chemistry Toward Heterocycles and Natural
Products; Padwa, A.; Pearson, W. H., Eds.; Wiley: New York, 2002, pp.
315–360; (b) Clark, J. S. in Nitrogen, Oxygen, and Sulfur Ylide Chemistry:
A Practical Approach in Chemistry; Clark, J. S. Ed.; Oxford Univ. Press:
Oxford, 2002, pp. 187–204.
(16)
For computational studies supporting a reversible and stepwise
mechanism of thiocarbonyl ylide [3+2]-cycloaddition reactions, see: (a)
Lan, Y.; Houk, K. N. Mechanism and Stereoselectivity of the Stepwise
1,3-Dipolar Cycloadditions between a Thiocarbonyl Ylide and Electron-
Deficient Dipolarophiles: A Computational Investigation. J. Am. Chem.
Soc. 2010, 132, 17921–17927; (b) Lan, Y.; Zou, L.; Cao, Y.; Houk, K. N.
Computational Methods to Calculate Accurate Activation and Reaction
Energies of 1,3-Dipolar Cycloadditions of 24 1,3-Dipoles. J. Phys. Chem.
A 2011, 115, 13906–13920.
(6)
The conjugate addition followed by C-alkylation of the formed
enolate is often characterized by low substrate control and selectivity
issues. For a review, see: Taylor, R. J. K. Organocopper Conjugate Addi-
tion-Enolate Trapping Reactions. Synthesis 1985, 4, 364–392.
(7)
(a) Speck, K.; Wildermuth, R.; Magauer, T. Convergent As-
sembly of the Tetracyclic Meroterpenoid (–)-Cyclosmenospongine by a
Non-Biomimetic Polyene Cyclization. Angew. Chem. Int. Ed. 2016, 55,
14131–14135; (b) Wildermuth, R.; Speck, K.; Haut, F.-L.; Mayer, P.;
Karge, B.; Brönstrup, M.; Magauer, T. A modular synthesis of tetracyclic
meroterpenoid antibiotics. Nat. Commun. 2017, 8, 2083.
(17)
For a single example of a thiocarbonyl ylide [6+3]-
cycloaddition reaction, see: (a) Tsuge, O.; Takata, T.; Noguchi, M. Cy-
cloaddition Reactions of 4,6-diphenylthieno [3,4-c]-1,2,5-oxadiazole and -
1,2,5-thiadiazole with 6,6-diphenylfulvene and Tropone. Chem. Lett.
1980, 9, 1031–1034; For related [6+3]-cycloaddition reactions of tropone,
see: (b) Trost, B. M.; Seoane, P. R. [6+3] Cycloaddition to nine-
membered ring carbocycles. J. Am. Chem. Soc. 1987, 109, 615–617; (c)
Du, Y.; Feng, J.; Lu, X. A Phosphine-Catalyzed [3+6] Annulation Reac-
tion of Modified Allylic Compounds and Tropone. Org. Lett. 2005, 7,
1987–1989; (d) Trost, B. M.; McDougall, P. J.; Hartmann, O.; Wathen, P.
(8)
(a) Aono, M.; Hyodo, C.; Terao, Y.; Achiwa, K. Generation of
ylides with release of disiloxane from
thiocarbonyl
bis(trimethylsilylmethyl) sulfoxides. Tetrahedron Lett. 1986, 27, 4039–
4042; (b) Erao, Y.; Aono, M.; Imai, N.; Achiwa, K. New Generation of
Thiocarbonyl Ylides from Organosilicon Compounds Containing Sulfur
and Their 1,3-Cycloadditions. Chem. Pharm. Bull. 1987, 35, 1734–1740;
ACS Paragon Plus Environment