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Burtoloso Group Meeting: Ketene Chemistry
Burtoloso Group Meeting: Ketene Chemistry
Ketene Chemistry:
From Discovery to Total Synthesis
Content
.1. A brief history of ketene
2. Ketene reactivity .
.3. Ketene preparation
4. Ketene in synthesis .
.5. Application in total synthesis 2
Burtoloso Group Meeting- Ketene Chemistry
1. A brief of history
Tidwell, T. T. (2005). The first century of ketenes (1905–2005): the birth of a versatile family of reactive
3
intermediates. Angewandte Chemie International Edition, 44(36), 5778-5785 .
Burtoloso Group Meeting- Ketene Chemistry
δCα=203-178 ppm
RMN-13C
δCβ=48-33 ppm
4
Tidwell TT. Ketenes. 2nd ed. Hoboken, NJ: Wiley Interscience; 2006
Burtoloso Group Meeting- Ketene Chemistry
Structure
Electronic and
Properties steric effects
Not Isolable Isolable
Substituents
5
Nguyen MT, Ha T, More O’Ferrall RA. J Org Chem. 1990;55:3251–3256.
Burtoloso Group Meeting- Ketene Chemistry
R ∆E(MP2)
H 3.9
Li 30.1 ∆E + Estável
MgH 23.2
AlH2 20.1
SiH3 11.5 ∆E - Estável
NH2 -9.3
OH -14.5
F -16.9
6
Boyd RJ, Edgecombe KE. J Am Chem Soc. 1988;110:4182–4186
Burtoloso Group Meeting- Ketene Chemistry
3. Ketene preparation
a. Kumar K, Kaur S, Ishar MPS. Synlett. 1999;8:1237–1238; b. Lang RW, Hansen H-J. Helv Chim Acta. 1980;63:438–455; c. Yamagami T, Hatsuda M, Utsugi M,
Kobayashi R, Moritani Y. Eur J Org Chem. 2013;33:7467–7470; d. Yamagami T, Moriyama N, Kyuhara M, et al. Org Proc Res Dev. 2014;18:437–445; e. Larsen 8
RD, Corley EG, Davis P, Reider PJ, Grabowski EJJ. J Am Chem Soc. 1989;111:7650–7651.
Burtoloso Group Meeting- Ketene Chemistry
77%
9
Yadav JS, Haldar A, Maity T. Eur J Org Chem. 2013;15:3076–3085;
Burtoloso Group Meeting- Ketene Chemistry
69%
This method was used in the acylation of a variety of resin bound peptides
10
.
Chandra K, Roy TK, Naoum JN, Gilon C, Gerber RB, Friedler A. Org Biomol Chem. 2014;12:1879–1884
Burtoloso Group Meeting- Ketene Chemistry
Reductive
Hydrogenation of palmitic acid using Ni/ZrO2 catalyst at 250°C proceeds through formation
of ketene as an adsorbed intermediate, ans this then reduced to the aldehyde.
11
Peng B, Zhao C, Kasakov S, Foraita S, Lercher JA. Chem Eur J. 2013;19:4732–4741 .
Burtoloso Group Meeting- Ketene Chemistry
Oxidative
Ketenes have been prepared for oxidation of acetic acid on a gold surface supported on
(TiO)2 which has been shown to involve formation of the gold ketenylidene specie.
12
a. Green IX, Tang W, Neurock M, Yates JT. Faraday Discuss. 2013;162:247–265; b. Green IX, Tang W, Neurock M, Yates JT. Acc Chem Res. 2014;47:805–815;
Burtoloso Group Meeting- Ketene Chemistry
Thermal Wolff
55%
13
Vidal A, Marin-Luna M, Alajarin M. Eur J Org Chem. 2014;4:878–886.
Burtoloso Group Meeting- Ketene Chemistry
Photochemical Wolff
83%
Allen AD, Fedorov AV, Fu N, Kobayashi S, Tidwell TT, Vukovic S, Badal MdMR, Mishima M. Can J Chem. in press.
Metal-catalyzed Wolff
80-91%
14
Burtoloso Group Meeting- Ketene Chemistry
78%
93%
Wang, J. et al. J. Am. Chem. Soc. 2011, 4330
15
Burtoloso Group Meeting- Ketene Chemistry
75%
17
Banzon A, Kuo JM, Miles BR, Fischer DR, Stang PJ, Raushel FM. Biochemistry. 1995;34:743–749;
Burtoloso Group Meeting- Ketene Chemistry
71%
18
Burtoloso Group Meeting- Ketene Chemistry
20
Surendra K, Rajendar G, Corey EJ. J Am Chem Soc. 2014;136:642–645.
Burtoloso Group Meeting- Ketene Chemistry
This work was extended to a one-pot multicomponent procedure involving two different
ketenes derived from diazo ketones
21
Mandler MD, Truong PM, Zavalij PY, Doyle MP. Org Lett. 2014;16:740–743.
Burtoloso Group Meeting- Ketene Chemistry
86%
22
Burtoloso Group Meeting- Ketene Chemistry
(60%, dr 83:17)
24
Mondal M, Ho H-J, Peraino NJ, Gary MA, Wheeler KA, Kerrigan NJ. J Org Chem. 2013;78:4587–4593.
Burtoloso Group Meeting- Ketene Chemistry
99%, 97% ee
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a. Schaefer C, Fu GC. Angew Chem Int Ed. 2005;44:4606–4608;
Burtoloso Group Meeting- Ketene Chemistry
Reber KP, Tilley SD, Carson CA, Sorensen EJ. J Org Chem. 2013;78:9584–9607.
26
Burtoloso Group Meeting- Ketene Chemistry
Excellent
Regiosselectivities
28
Mohanan K, Presset M, Mailhol D, Coquerel Y, Rodriguez J. Chem Eur J. 2012;18: 9217–9220.
Burtoloso Group Meeting- Ketene Chemistry
Wittig reagent was formed in solution reacts with methylketene also generated in situ to
give a ketene-Wittig reaction forming de product allene.
29
Xu S, Zhu S, Shang J, Zhang J, Tang Y, Dou J. J Org Chem. 2014;79:3696–3703
Burtoloso Group Meeting- Ketene Chemistry
30
.
Aida, T. et al. J. Am. Chem. Soc. 2011, 2840
Burtoloso Group Meeting- Ketene Chemistry
Ginkgolide B
Active
biological
terpene lactons
present in
Ginkgo biloba
31
Corey et al. J. Am. Chem. Soc. 1998, 649.
Burtoloso Group Meeting- Ketene Chemistry
Epicoccins derivative
Is a species of fungus, in
the phylum Ascomycota
32
.
Brase, S et al. Chem. Eur. J. 2016, 11624
Burtoloso Group Meeting- Ketene Chemistry
Macrocidin A
(+)-FR900482
Antitumor agent
34
.
Danheiser, R. L. et al. J. Org. Chem. 2011, 1852