First author et al.
Report
dehydration with aqueous HCl, led to the formation of the
mixture of 3gi and product 3gi’.[2c] Furthermore, the methylation
of the deuterium labelled substrate 1w was also conducted, and
the desired product 3wi was obtained as the single product in 76%
yield, while relatively poor regioselectivity was observed when
using traditional method (Scheme 4b). [2c] Therefore, the current
method could be a promising candidate for preparing the
site-fixed deuterated product.
As that enolate was demonstrated as the key intermediate,
acid-sensitive functional groups, such as tertiary alcohol, should
be tolerated in this catalytic system. As we expected, the desired
product 3xa was obtained exclusively in 50% isolated yield using
the presented catalytic system (Scheme 4c). The conversion of 1x
Acknowledgement
Support of this work by the “973” Project from the MOST
(2015CB856600 and 2013CB228102) and NSFC (Nos. 21332001
and 21431008) is gratefully acknowledged.
References
[1] a) Ichiba, T.; Yoshida, W. Y.; Scheuer, P. J.; Higa, T.; Gravalos, D. G., J.
Am. Chem. Soc. 1991, 113, 3173; b) Höfle, G.; Bedorf, N.; Steinmetz,
H.; Schomburg, D.; Gerth, K.; Reichenbach, H., Angew. Chem. Int. Ed.
1996, 35, 1567.
[2] a) de Meijere, A., Diederich, F., Metal-Catalyzed Cross-Coupling,
Wiley-VCH: Weinheim, 2004; b) Itami, K.; Yoshida, J.-i., Bull. Chem.
Soc. Jpn. 2006, 79, 811; c) Smith, M. B.; March, J., March's advanced
organic chemistry: reactions, mechanisms, and structure, John Wiley
& Sons, 2007.
[3] a) Miyaura, N.; Suzuki, A., Chem. Rev. 1995, 95, 2457; b) Buchwald, S.
L.; Fugami, K.; Hiyama, T.; Kosugi, M.; Miura, M.; Miyaura, N.; Muci,
A.; Nomura, M.; Shirakawa, E.; Tamao, K., Cross-coupling reactions: a
practical guide, Vol. 219, Springer, 2003.
[4] a) Beletskaya, I. P.; Cheprakov, A. V., Chem. Rev. 2000, 100, 3009; b)
Oestreich, M., The Mizoroki-Heck Reaction, John Wiley & Sons, 2009;
c) Coeffard, V.; Guiry, P. J., Curr. Org. Chem. 2010, 14, 212.
[5] a) Schuster, M.; Blechert, S., Angew. Chem. Int. Ed. 1997, 36, 2036; b)
Grubbs, R. H.; O'Leary, D. J., Handbook of Metathesis, Volume 2:
Applications in Organic Synthesis, John Wiley & Sons, 2015; c)
Grubbs, R. H.; Chang, S., Tetrahedron 1998, 54, 4413; d) Fürstner, A.,
Angew. Chem. Int. Ed. 2000, 39, 3012; e) Trnka, T. M.; Grubbs, R. H.,
Acc. Chem. Res. 2001, 34, 18.
was also conducted using Zhou’s conditions, and only
a
di-olefinated product 3xa’ was observed in a good yield. [9] Under
the standard conditions, we also conducted the phenylation of
ketone 1y, and yielded the compound 1yg in 80% yield with
moderate Z/E selectivity (E/Z = 5.5). If LDA was used as the base
instead of NaH, product 1yg could be obtained in 75% yield with
high Z/E ratio (E/Z = 14). In comparison, Zhou’s method was also
applied to the conversion of 1y while only low selectivity was
observed for the products (Scheme 4d). [9]
Conclusions
In summary, we demonstrated a general and direct protocol
to convert carbonyl compounds to substituted olefins via enolate
intermediate. Besides ketones, aldehydes were proved to be
suitable for this method. The conversion of ketones to alkenes
with methyl magnesium iodide was also conducted with good
yield and ideal regioselectivity. Acid-sensitive functional groups,
such as tertiary alcohol, could be tolerated. Preliminary
mechanism studies ruled out the participation of alcohol and
olefin as key intermediates. Therefore, this research could be a
helpful update for the enol chemistry. Now we are still working on
expanding the substrate scope and the detailed reaction
mechanism.
[6] Kurti, L.; Czakó, B., Strategic applications of named reactions in
organic synthesis, Elsevier, 2005.
[7] a) Maercker, A., The wittig reaction, Wiley Online Library, 1965; b)
Pommer, H., Angew. Chem. Int. Ed. 1977, 16, 423; c) Maryanoff, B. E.;
Reitz, A. B., Chem. Rev. 1989, 89, 863; d) Takeda, T., Modern
Carbonyl Olefination: Methods and Applications, John Wiley & Sons,
2006.
[8] a) Katritzky, A. R.; Ley, S. V.; Meth-Cohn, O.; Rees, C. W.,
Comprehensive Organic Functional Group Transformations: Synthesis:
carbon with one heteroatom attached by a single bond, Vol. 2,
Elsevier, 1995; b) Schreiber, S. L., Science 2000, 287, 1964; c) Larock,
R., Comprehensive Organic Transformations, VCH, New York, 2001; d)
Mundy, B. P.; Ellerd, M. G.; Favaloro Jr, F. G., Name reactions and
reagents in organic synthesis, John Wiley & Sons, 2005.
[9] Lei, C.; Yip, Y. J.; Zhou, J. S., J. Am. Chem. Soc. 2017, 139, 6086.
[10] a) Li, B.-J.; Yu, D.-G.; Sun, C.-L.; Shi, Z.-J., Chemistry – A European
Journal 2011, 17, 1728; b) Yu, D.-G.; Li, B.-J.; Shi, Z.-J., Acc. Chem. Res.
2010, 43, 1486; c) Su, B.; Cao, Z.-C.; Shi, Z.-J., Acc. Chem. Res. 2015,
48, 886; d) Zarate, C.; van Gemmeren, M.; Somerville, R. J.; Martin, R.,
Adv. Organomet. Chem. 2016, 66, 143; e) Cornella, J.; Zarate, C.;
Martin, R., Chem. Soc. Rev. 2014, 43, 8081; f) Rosen, B. M.; Quasdorf,
K. W.; Wilson, D. A.; Zhang, N.; Resmerita, A.-M.; Garg, N. K.; Percec,
V., Chem. Rev. 2011, 111, 1346; g) Tobisu, M.; Chatani, N., Acc. Chem.
Res. 2015, 48, 1717; h) Tollefson, E. J.; Hanna, L. E.; Jarvo, E. R., Acc.
Chem. Res. 2015, 48, 2344.
Experimental
General method for the conversion of carbonyl compound 1a
to olefin 3aa: In a nitrogen-filled glove-box, a 25 mL oven-dried
seal-tube equipped with a magnetic stir bar was charged with
ketone 1a (0.2 mmol, 26.9 mg), NaH (0.24 mmol, in mineral oil),
then THF (1 mL) was added via syringe. The mixture was stirred
for 1 hours, and then the solvent THF was removed with a cold
trap under reduced pressure. Catalyst Ni(cod)2 (0.01 mmol, 5.6
mg), ligand PCy3 (0.04 mmol, 22.4 mg), and PhMe (0.6 mL) were
added. Next, Grignard reagent 2a (0.4 mmol in Et2O) was added
via syringe. The reaction was removed from the glove-box and
maintained at 70 oC for 24 h in an oil-bath. Then, the reaction was
quenched by EtOH (1.5 mL). The desired products were purified
by flash chromatography on silica gel (petroleum ether), and 3aa
obtained as colourless oil in 88% yield (34.2 mg).Analytical data
for 3aa: 1H NMR (400 MHz, CDCl3) δ 7.38 – 7.32 (m, 2H), 7.28 (d, J
= 7.2 Hz, 1H), 7.26 – 7.14 (m, 7H), 6.16 (q, J = 7.0 Hz, 1H), 1.75 (d, J
= 7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 142.94, 142.43, 140.00,
130.03, 128.12, 128.03, 127.17, 126.80, 126.69, 124.10, 15.68;
MS (EI): 198 (M+).
[11] a) Fan, L.; Jia, J.; Hou, H.; Lefebvre, Q.; Rueping, M., Chemistry – A
European Journal 2016, 22, 16437; b) Li, B. X.; Le, D. N.; Mack, K. A.;
McClory, A.; Lim, N.-K.; Cravillion, T.; Savage, S.; Han, C.; Collum, D.
B.; Zhang, H.; Gosselin, F., J. Am. Chem. Soc. 2017, 139, 10777; c)
Mack, K. A.; McClory, A.; Zhang, H.; Gosselin, F.; Collum, D. B., J. Am.
Chem. Soc. 2017, 139, 12182.
Supporting Information
The supporting information for this article is available on the
[12] a) Hansen, A. L.; Ebran, J.-P.; Gøgsig, T. M.; Skrydstrup, T., The
Journal of Organic Chemistry 2007, 72, 6464; b) Cahiez, G.; Habiak, V.;
Gager, O., Org. Lett. 2008, 10, 2389; c) Gauthier, D.; Beckendorf, S.;
Gøgsig, T. M.; Lindhardt, A. T.; Skrydstrup, T., The Journal of Organic
Chemistry 2009, 74, 3536; d) Sahlberg, C.; Quader, A.; Claesson, A.,
4
© 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2019, 37, XXX-XXX
This article is protected by copyright. All rights reserved.