3
1
2
stereogenic center was obtained with an enantioselectivity
as high as 83% ee (Scheme 3).20
40 ACKNOWLEDGMENT
41 This work was supported by Grants-in-Aid for Scientific
42 Research (B) (No. 15H03803), JSPS, to H.O. and by
43 CREST and ACT-C, JST, to M.S. K.H. thanks JSPS for
44 scholarship support.
[CuOTf·(toluene)0.5]/L2
(9-BBN-H)2
(0.5 eq)
BnO
BnO
BnO
BnO
(10 mol%)
*
mesitylene
KOMe (1.1 eq)
60 °C, 1 h mesitylene/MTBE (1:3)
25 °C, 13 h
(E)-4a
5a
55%, 83% ee
45 References and Notes
Cl
3
4
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
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95
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98
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103
104
105
106
107
1
For reviews on Cu-catalyzed enantioselective allylic substitutions
with organomagnesium, organozinc or organoaluminum reagents,
see: (a) A. H. Hoveyda, A. W. Hird, M. A. Kacprzynski, Chem.
Commun. 2004, 1779–1785. (b) H. Yorimitsu, K. Oshima,
Angew. Chem. Int. Ed. 2005, 44, 4435–4439. (c) C. A. Falciola,
A. Alexakis, Eur. J. Org. Chem. 2008, 3765–3780. (d) A.
Alexakis, J. E. Bäckvall, N. Krause, O. Pàmies, M. Diéguez,
Chem. Rev. 2008, 108, 2796–2823. (e) S. R. Harutyunyan, T. den
Hartog, K. Geurts, A. J. Minnaard, B. L. Feringa, Chem. Rev.
2008, 108, 2824–2852.
For reviews on transition metal catalyzed allylic substitutions
with organoboron compounds, see: (a) F. C. Pigge, Synthesis
2010, 1745–1762. (b) R. Shintani, Synthesis 2016, 1087–1100.
For Ni-catalyzed enantioselective allylic substitution of
arylboronic acids, see: K.-G. Chung, Y. Miyake, S. J. Uemura,
Chem. Soc. Perkin Trans. 1 2000, 15–18.
For Cu-catalyzed enantioselective allylic substitutions with allyl-,
aryl-, alkenyl- and allenylboronates, see: (a) R. Shintani, K.
Takatsu, M. Takeda, T. Hayashi, Angew. Chem. Int. Ed. 2011, 50,
8656–8659. (b) B. Jung, A. H. Hoveyda, J. Am. Chem. Soc. 2012,
134, 1490–1493. (c) F. Gao, J. L. Carr, A. H. Hoveyda, Angew.
Chem. Int. Ed. 2012, 51, 6613–6617. (d) Y. Yasuda, H.
Ohmiya, M. Sawamura, Angew. Chem. Int. Ed., 2016, 55,
10816–10820.
For Pd-catalyzed enantioselective allylic substitutions with
allylboronates, see: (a) P. Zhang, L. A. Brozek, J. P. Morken, J.
Am. Chem. Soc. 2010, 132, 10686–10688. (b) P. Zhang, H. Le, R.
E. Kyne, J. P. Morken, J. Am. Chem. Soc. 2011, 133, 9716–9719.
(c) L. A. Brozek, M. J. Ardolino, J. P. Morken, J. Am. Chem. Soc.
2011, 133, 16778–16781.
For Rh-catalyzed enantioselective allylic substitution of cis-4-
cyclopenten-1,3-diol derivatives with arylboronic acids, see: (a)
F. Menard, T. M. Chapman, C. Dockendorff, M. Lautens, Org.
Lett. 2006, 8, 4569–4572. (b) F. Menard, D. Perez, D. S. Roman,
T. M. Chapman, M. Lautens, J. Org. Chem. 2010, 75, 4056–
4068. For Rh-catalyzed enantioselective allylic substitution of
(Z)-2-butene-1,4-diol derivatives with arylboron compounds, see:
(c) T. Miura, Y. Takahashi, M. Murakami, Chem. Commun. 2007,
595–597. (d) B. Yu, F. Menard, N. Isono, M. Lautens, Synthesis
2009, 853–859. For Rh-catalyzed enantioselective allylic
substitution of allylic ethers with arylboronic acids, see: (e) H.
Kiuchi, D. Takahashi, K. Funaki, T. Sato, S. Oi, Org. Lett. 2012,
14, 4502–4505.
For copper-catalyzed γ-selective and stereospecific allylic
substitutions of secondary allylic phosphates with alkyl-9-BBN
reagents, see: (a) H. Ohmiya, U. Yokobori, Y. Makida, M.
Sawamura, J. Am. Chem. Soc. 2010, 132, 2895–2897. (b) K.
Nagao, H. Ohmiya, M. Sawamura, Synthesis 2012, 1535–1541;
(c) K. Nagao, U. Yokobori, Y. Makida, H. Ohmiya, M.
Sawamura, J. Am. Chem. Soc. 2012, 134, 8982–8987. see also:
(d) A. M. Whittaker, R. P. Rucker, G. Lalic, Org. Lett. 2010, 12,
3216–3218. (e) H. Ohmiya, U. Yokobori, Y. Makida, M.
Sawamura, Org. Lett. 2011, 13, 6312–6315.
Scheme 3. Construction of a Quaternary Carbon Stereogenic Center.
5
6
7
8
9
A possible reaction pathway for the intramolecular
allylic alkylation catalyzed by the CuX-L2 system (A, CuX-
P, X = Cl or OMe) is proposed in Figure 1.8 Similarly to the
intermolecular
intramolecular
reaction
reaction
reported
should be
previously,
initiated
this
by
10 transmetalation between the copper(I) complex A and borate
11 B, which is formed from 2 and KOMe, to produce a neutral
12 alkylcopper(I) complex (C) coordinated with the
13 monophosphine L2 (P) and the alkene moiety of the allylic
14 substrate.21 The intramolecular η2-coordination of the alkene
15 in C should be more feasible than the coordination of alkene
16 in the intermolecular allylic alkylation. This difference in
17 alkene coordination may be a cause of the experimentally
18 observed difference in preferred denticity for phosphine
2
3
4
19 coordination. Next, the alkylcopper(I) intermediate
C
20 undergoes C–Cu addition across the bound C–C double
21 bond, forming E. Then, Cu–Cl elimination affords 3 and
22 regenerates A for the next catalytic cycle.
5
6
K+
−
MeO
B
R
R
R
R
H
CuX
P
B
3
A
Cl
X = OMe, Cl
elimination
+
KX
9-BBN-OMe
P
P
Cu
H
Cu
H
R
CH2Cl
CH2Cl
R
H
H
R
R
C
E
P
Cu
R
addition
(insertion)
CH2Cl
R
H
H
D-TS
23
24 Figure 1. A possible reaction pathway for the copper-catalyzed
25 intramolecular allylic alkylation of an alkyl-9-BBN derivative.
7
26
In summary, we developed the reductive cyclization
27 reaction of allyl chlorides tethered to a terminal alkene via
28 alkene hydroboration followed by in-situ enantioselective
29 intramolecular
30 intermediates catalyzed by a copper(I)-phosphoramidite
31 system. The reaction afforded functionalized chiral cyclic
32 compounds bearing enantioenriched tertiary or quaternary
33 carbon stereogenic centers.
allylic
alkylation
of
organoboron
8
9
(a) Y. Shido, M. Yoshida, M. Tanabe, H. Ohmiya, M. Sawamura,
J. Am. Chem. Soc. 2012, 134, 18573–18576. (b) K. Hojoh, Y.
Shido, H. Ohmiya, M. Sawamura, Angew. Chem. Int. Ed. 2014,
53, 4954–4958.
34
35 Supporting Information.
For and reviews or
a book on transition metal-catalyzed
36 Experimental details and characterization data for all new
37 compounds (PDF). This material is available free of charge
39
enantioselective intramolecular allylic substitutions, see: (a) Z.
Lu, S. Ma, Angew. Chem. Int. Ed. 2008, 47, 258–297. (b) C.
Kammerer, G. Prestat, D. Madec, G. Poli, Acc. Chem.
Res. 2014, 47, 3439–3447. (c) C.-X. Zhuo, C. Zheng, S.-L. You,