Journal of the American Chemical Society
Page 4 of 5
Swansea University. We thank Dr Robert Phipps for
of allylic alcohols may be compatible with this enantiose-
lective process; studies towards this ideal are ongoing.
1
2
3
useful discussion.
Scheme 2. Preliminary SPRs on acyclic alkenes
REFERENCES
4
5
6
7
8
9
Me Me
(1) For reviews on SPRs, see: (a) Song, Z.-L.; Fan, C.-A.; Tu, Y.-Q. Chem.
Rev., 2011, 111, 7523. (b) Corey, E. J.; Guzman-Perez, A. Angew. Chem.,
Int. Ed., 1998, 37, 388. (c) Snape, T. J. Chem. Soc. Rev. 2007, 36, 1823.
(2) For exmaples of SPRs in total synthesis using allylic alcohols, see: (a)
Reisman, S. E.; Ready, J. M.; Weiss, M. M.; Hasuoka, A.; Hirata, M.;
Tamaki, K.; Ovaska, T. V.; Smith, C. J.; Wood, J. L. J. Am. Chem. Soc.,
2008, 130, 2087. (b) Hamura, T.; Suzuki, T.; Matsumoto, T.; Suzuki, K.
Angew. Chem., Int. Ed., 2006, 45, 6294. (c) Trost, B. M.; Mao, M. K. T.;
Balkovec, J. M.; Buhlmayer, P. J. Am. Chem. Soc. 1986, 108, 4965. (d)
Trost, B. M.; Balkovec, J. M.; Mao, M. K. T. J. Am. Chem. Soc. 1986, 108,
4974. (e) Fan, C.-A.; Tu, Y.-Q.; Song, Z.-L.; Zhang, E.; Shi, L.; Wang, M.;
Wang, B.; Zhang, S.-Y. Org. Lett., 2004, 6, 4691. (f) Angeles, A. R.; Waters,
S. P.; Danishefsky, S. J. J. Am. Chem. Soc., 2008, 130, 13765.
O
HO
O
O
EtO
EtO
N
N
12a. 62% yield
d.r. 2.6:1
e.r. 89:11
Cu
Ph
Ph
TfO
OTf
Me
Me
10mol% (R,R)-3•Cu(OTf)2
2c, DTBP, CH2Cl2, 25 ˚C, 24 h
11a
Me Me
O
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
O
O
HO
Me
N
N
12b. 41% yield
e.r. 76:24
Me
Cu
Ph
Ph
TfO
OTf
10mol% (R,R)-3•Cu(OTf)2
2c, Na2CO3, CH2Cl2, 30 ˚C, 24 h
11b
In summary, we have developed an enantioselective
(3) For a review on catalytic enantioselective SPRs, see: Wang, S.-H.; Li,
B.-S.; Tu, Y.-Q. Chem. Commun., 2014, 50, 2393.
Cu-catalyzed arylative SPR using diaryliodonium salts,
which transforms allylic alcohols into spirocyclic ketones
in high yield and enantiomeric ratios. The enantioenriched
spirocyclic ketones display vincinal a,a’-quaternary and b-
aryl tertiary centers,10 often as single diastereomers, and
can undergo complexity-generating reactions to a variety of
novel molecular scaffolds. This operationally simple pro-
cess uses readily available starting materials and a com-
mercial catalyst and bisoxazoline ligand, which we believe
will be useful to practitioners of chemical synthesis.
(4) For an example of an enantioselective halogenative SPR, see: (a) Ro-
manov-Michailidis, F.; Guénée, L.; Alexakis, A. Angew. Chem. Int. Ed.,
2013, 52, 9266. For examples of enantioselective epoxidation-driven SPRs,
see: (b) Maruoka, K.; Ooi, T.; Nagahara, S.; Yamamoto, H. Tetrahedron,
1991, 47, 6983. (c) Nemoto, H.; Nagamochi, M.; Ishibashi, H.; Fukumoto,
K. J. Org. Chem., 1994, 59, 74. For an example of an enantioselective
Brϕnsted acid-catalyzed SPR, see: (d) Zhang, Q.-W.; Fan, C.-A.; Zhang,
H.-J.; Tu, Y.-Q.; Zhao, Y.-M.; Gu, P.; Chen, Z.-M. Angew. Chem., Int. Ed.,
2009, 48, 8572. For examples of a Pd-catalyzed SPRs, see: (e) Yoshida, M.;
Ismail, M. A. H.; Nemoto, H.; Ihara M. J. Chem. Soc., Perkin Trans. 1,
2000, 16, 2629. (f) Trost, B. M.; Yasukata, T. J. Am. Chem. Soc. 2001, 123,
7162. For examples of Au-catalyzed SPRs, see: (g) Sethofer, S. G.; Staben,
S. T.; Hung, O. Y.; Toste, F. D. Org. Lett., 2008, 10, 4315. (h) Klienbeck,
F.; Toste, F. D. J. Am. Chem. Soc. 2009, 131, 9178. For an example of an
enantioselective Pd/Brϕnsted acid-catalyzed SPR, see: (i) Chai, Z.; Rainey,
T. J. J. Am. Chem. Soc., 2012, 134, 3615.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on
the ACS Publications website at DOI:
############################
.
(5) For rare examples of carbon-electrophile initiated catalytic SPRs, see:
(a) Zhang, Q.-W.; Zhang, X.-B.; Li, B.-S.; Xiang, K.; Zhang, F.-M.; Wang,
S.-H.; Tu, Y.-Q. Chem. Commun., 2013, 49, 1648. (b) Yang, B.-M.; Cai, P.-
J.; Tu, Y.-Q.; Yu, Z.-X.; Chen, Z.-M.; Wang, S.-H.; Wang, S.-H.; Zhang, F.-
M. J. Am. Chem. Soc., 2015, 137, 8344. (c) Shu, X. -Z.; Zhang, M.; He, Y.;
Frei, H.; Toste, F. D. J. Am. Chem. Soc. 2014, 136, 5844.
Experimental procedures and characterization data for all
compounds (PDF)
Crystallographic data for 5c (CIF)
AUTHOR INFORMATION
(6) (a) Bigot, A.; Williamson, A. E.; Gaunt, M. J. J. Am. Chem. Soc. 2011
,
133, 13778. (b) Cahard, E.; Male, H. P. J.; Tissot, M.; Gaunt, M. J. J. Am.
Chem. Soc. 2015, 137, 7986.
(7) (a) Harvey, J. S.; Simonovich, S. P.; Jamison, C. R.; MacMillan, D. W.
C. J. Am. Chem. Soc. 2011, 133, 13782. (b) Zhu, S.; MacMillan, D. W. C. J.
Am. Chem. Soc. 2012, 134, 10815. For an example of a diastereoselective
Cu-catalyzed indole arylation, see: (c) Kieffer, M. E.; Chuang, K. V.;
Reisman, S. E. J. Am. Chem. Soc. 2013, 135, 5557.
(8) Phipps, R. J.; McMurray, L.; Ritter, S.; Duong, H. A.; Gaunt, M. J. J.
Am. Chem. Soc. 2012, 134, 10773.
(9) For a recent example of a catalytic enantioselective synthesis of spiro-
ketones, see Rahemtulla, B. F.; Clark, H. F.; Smith, M. D. Angew. Chem.
Int. Ed. 2016, 55, 13180.
Corresponding Author
Notes:
The authors declare no competing financial interests.
ACKNOWLEDGMENT
We are grateful to EPSRC (EP/100548X/1), ERC
(ERC-STG-259711) and the Royal Society (Wolfson
Award) for supporting this research (M.J.G.). We also
thank the Agency for Science Technology and Re-
search (A*STAR, Singapore) for a PhD scholarship
(D.H.L.) Mass spectrometry data were acquired at the
EPSRC UK National Mass Spectrometry Facility at
(10) For review on generating quaternary carbon stereocenters, see: (a)
Douglas, C. J.; Overman, L. E. Proc. Natl. Acad. Sci. USA 2004, 101, 5363.
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