614
T. Ozaki, Y. Kobayashi
Letter
Synlett
Acknowledgment
1) TPAP, NMO
OH
OH
This study was supported by a Grant-in-Aid for Scientific Research
from the Ministry of Education, Culture, Sports, Science, and Technol-
ogy, Japan (26410111).
2) MeMgCl
84%
10
rac-11
Supporting Information
OH
t-BuOOH (1 equiv)
OR
Supporting information for this article is available online at
+
S
u
p
p
ortiInfogrmoaitn
S
u
p
p
o
nrtogI
f
rmoaitn
L-(+)-DIPT/Ti(O-i-Pr)4
O
(1.5:1)
(R)-11, R = H
12
27% yield, 97% ee
References and Notes
PyCO2H
(R)-8, R = PyCO
Et3N, DMAP
[N-Me-2-Cl-C5H4N]+ I–
(1) (a) Das, J. P.; Marek, I. Chem. Commun. 2011, 47, 4593.
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87%
Scheme 3 Synthesis of (R)-8
Table 3 Chirality Transfer of the Substitution Reaction Using (R)-8a
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ArX (3.2 equiv), t-BuLi (6 equiv)
CuTC (1.6 equiv), MgBr2 (6.4 equiv)
Ar
(R)-8
THF, Et2O
–40 to –20 °C, 2 h
(R)-9a,e,f
Entry ArX
Product 9b Yield (%)
ee (%)c
CT (%)d
1
2
3
4
PhBr
(R)-9a
(R)-9e
(R)-9e
(R)-9ff
85
87
91
78
95
96
97
98
4-MeOC6H4Br
4-MeOC6H4I
4-FC6H4Br
87
89e
>95g
>95g
a Prepared from alcohol (R)-11 of 98% ee; see ref 14.
b 97–99% regioselectivity.
c The ee was determined by chiral HPLC.
d CT: chirality transfer.
e A repeated reaction with a similar reaction scale [ca. 50 mg of (R)-8] af-
forded (R)-9e with 91% CT in 93% yield.
f Absolute configuration was determined by comparison with (R)-9e.
g Baseline separation was not attained on six chiral HPLC columns (see the
Supporting Information).
In summary, aryl copper reagents derived from aryllith-
ium and copper(I) thiophene-2-carboxylate were devel-
oped for the allylic substitution of γ,γ-disubstituted sec-
ondary allylic picolinates to afford quaternary stereogenic
carbons. Aryllithium reagents prepared by bromine–lithi-
um exchange and ortho lithiation were examined and were
found to result in high efficiency in terms of reactivity and
regio- and stereoselectivity. Fairly large substituents in the
ortho position marginally affected the reioselectivity and
reactivity of the reaction. Furthermore, the anti-SN2′ path-
way of the reaction was established.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, 611–615