Construction of quaternary carbon centers by using substitution of γ,γ-disubstituted secondary allylic picolinates with alkylcopper reagents

Article abstract of DOI:10.1016/j.tetlet.2013.06.046

ZnI₂ was found to promote regio- and stereoselective substitution of γ,γ-disubstituted secondary allylic picolinates with alkylcopper reagents derived from alkyl-MgBr and CuBr·Me₂S in a 2:1 ratio to furnish quaternary carbon centers in good yields. Alkyl groups delivered efficiently were the primary, secondary, and benzyl classes such as Me, Et, Bu, C₁₆H₃₃, Ph(CH₂)₂, Ph(CH₂)₃, c-C₆H₁₁, and Bn. As an application, allylic picolinates with the (E)- or (Z)-olefin afforded quaternary carbon centers that are the enantiomers of each other.

Full text of DOI:10.1016/j.tetlet.2013.06.046

Tetrahedron Letters 54 (2013) 4629–4632
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Construction of quaternary carbon centers by using substitution of
c,c-disubstituted secondary allylic picolinates with alkylcopper
reagents
⇑
Chao Feng, Yuki Kaneko, Yuichi Kobayashi
Department of Bioengineering, Tokyo Institute of Technology, Box B52, Nagatsuta-cho 4259, Midori-ku, Yokohama 226-8501, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
ZnI2 was found to promote regio- and stereoselective substitution of c,c-disubstituted secondary allylic
Received 17 May 2013
Revised 6 June 2013
Accepted 11 June 2013
Available online 18 June 2013
picolinates with alkylcopper reagents derived from alkyl-MgBr and CuBrꢀMe2S in a 2:1 ratio to furnish
quaternary carbon centers in good yields. Alkyl groups delivered efficiently were the primary, secondary,
and benzyl classes such as Me, Et, Bu, C16H33, Ph(CH2)2, Ph(CH2)3, c-C6H11, and Bn. As an application,
allylic picolinates with the (E)- or (Z)-olefin afforded quaternary carbon centers that are the enantiomers
of each other.
Keywords:
Ó 2013 Elsevier Ltd. All rights reserved.
Quaternary carbon
Allylic substitution
Alkylcopper reagents
Regioselectivity
Chirality transfer
Organocopper reagents have been successfully applied for
allylic substitution, representing one of the most valuable methods
to form C–C bonds,1 especially in connection with the construction
of chiral quaternary carbon centers, which is a great challenge dur-
ing the past decades2 and oftentimes the key step for the synthesis
of important natural products.3 Since the asymmetric preparation
of secondary allylic alcohols with high enantiomeric purity is well
investigated,4 allylic substitution of the derived esters with excel-
lent chirality transfer (CT) offers one of the most essential methods
to generate all-carbon quaternary stereo centers.1 For instance,
Breit et al reported an interesting protocol via o-DPPB-directed
allylic substitution, affording chiral quaternary carbon centers re-
gio- and stereoselectively.5 Knochel and co-workers on the other
hand applied the C6F5CO2 leaving group to asymmetrically synthe-
size quaternary carbons, which were then successively trans-
formed into chiral tertiary alcohols and amines.6 In contrast,
Spino designed secondary allylic pivaloates possessing a chiral
auxiliary to afford the quaternary products regioselectively.7
Recently, we have introduced the PyCO2 leaving group to estab-
lish allylic substitution of secondary allylic esters,8 and the proto-
col was applied for the construction of all carbon quaternary
centers on cyclic and acyclic structures (Scheme 1, A).8d,8e In the
and Cu(acac)2 in the 2:1 ratio.8e Later, this reagent system was ap-
plied to BuCu(acac)MgBr, a representative alkylcopper reagent, to
produce a mixture of products, among which the desired SN20
latter case, an aryl (Ar) group was delivered to the
c position by
using ArCu(acac)MgBr, which was in turn derived from ArMgBr
Scheme 1. Previous and present worka.rs, regioselectivity; ds, diastereomeric
selectivity between alkyl and R groups.
⇑
Corresponding author. Tel./fax: +81 45 924 5789.
E-mail address: ykobayas@bio.titech.ac.jp (Y. Kobayashi).
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.06.046

4630
C. Feng et al. / Tetrahedron Letters 54 (2013) 4629–4632
Table 1
Condition optimization
Entry
Butylcopper reagent (equiv)
ZnI2 (equiv)
Temp. (oC)
Product ratio
Regioselectivity
5a:6a
5a:6a:7:1a
1
2
3
4
5
6
7
8
BuCu (1.5)
BuCu (1.5)
—
1.5
—
1.5
—
1.5
1.0
0.5
–18
–18
–18
–18
–40
–40
–40
–40
75:4:3:18
44:4:2:50
33:56:11:0
96:4:0:0
54:46:0:0
>99:1:0:0b
97:2:1:0
95:5
92:8
36:74
96:4
54:46
>99:1
98:2
97:3
Bu2CuMgBr (1.5)
Bu2CuMgBr (1.5)
Bu2CuMgBr (1.5)
Bu2CuMgBr (1.5)
Bu2CuMgBr (1.5)
Bu2CuMgBr (1.5)
92:3:5:0
a
Determined by 1H NMR analysis of unpurified reaction mixtures.
Combined isolated yield of 5a and 6a, 91%.
b
product was detected by 1H NMR and TLC analyses. Herein, we
wish to report our continuous investigation of finding alkylcopper
reagents for the construction of chiral quaternary carbon centers
by allylic substitution of optically active acyclic picolinates
(Scheme 1B).
Table 3
Allylic substitution of 1 with various alkylcopper reagents
R2CuMgBr (1.5equiv)
ZnI2 (1.5 equiv)
R
1
+
R
(CH2)3C6H5
At the beginning of our study, racemic picolinate 18e was syn-
thesized for condition optimization, and two types of butylcopper
reagents of the formal ‘BuCu’ and ‘Bu2Cuꢁ’ structures were gener-
ated by using BuMgBr and CuBr Me2S in 1:1 and 2:1 ratios, respec-
tively.9 The product distribution was calculated based on the
integration ratios of the corresponding olefinic protons in the 1H
NMR spectra of the unpurified reaction mixtures. As summarized
in Table 1, the former ‘BuCu’ species at –18 °C gave SN20 product
5a (no cis product was detected by 1H NMR) in 95% regioselectivity
over SN2 product 6a,10 though the reaction did not complete (entry
1). On the other hand, ‘Bu2Cuꢁ’ species gave a mixture of 5a and 6a
at –18 oC and even at –40 oC (entries 3 and 5). Next, ZnI2 was em-
ployed with the ‘BuCu’ species in consequence of the importance of
Zn salts to the regioselectivity discovered previously,8d but the
reaction was retarded (entry 2). On the other hand, ZnI2 enhanced
regioselectivity of the reaction with the ‘Bu2Cuꢁ’ species to 96% at
ꢁ18 oC (entry 4) and to almost perfection at ꢁ40 oC (entry 6). Even
with less quantity of ZnI2 (1.0 equiv and 0.5 equiv), high regiose-
lectivity was still observed (entries 7 and 8). In these reactions,
ZnI2 probably chelates to the Py ring more strongly than MgBr2
to gain enough reactivity and regioselectivity. However, ZnI2 works
well only for the ‘Bu2Cuꢁ’ reagent, and not for the ‘BuCu’ reagent
(entries 2 vs 4).
THF, –40 oC, 1–2 h
5
6
Entry
R
SN20
product
5:6a
Yieldb (%)
1
2
3
4
5
6
7
8
Me
5b
5c
5d
5e
5f
5g
5h
5i
99:1
98:2
98:2
>99:1
98:2
98:2
92:8
32:68
88
84
95
94
Et
Bnc
C6H5(CH2)2
C6H5(CH2)3
87
C
16H33
>99
90
Cy
t-Buc
38d
a
b
c
Determined by 1H NMR analysis of unpurified reaction mixtures.
Isolated yield after purification by chromatography.
BnMgCl and t-BuMgCl were used in entries 3 and 8, respectively.
d
No picolinate remained by TLC and 1H NMR analysis of unpurified reaction
mixtures.
incomplete (entries 1, 2). Other salts such as ZnBr2, Zn(OCOPh)2,
and Zn(OTs)2 showed 93–96% regioselectivity, whereas the selec-
tivity by Zn(OAc)2 was somewhat low (entries 3–6). In contrast,
Zn(OSO2CF3)2 gave a mixture of the regioisomers. In summary,
ZnI2 was confirmed to be the most effective zinc salt that provides
high levels of the regioselectivity, whereas ZnBr2, Zn(OCOPh)2, and
Zn(OTs)2 showed a slightly lower selectivity, thus being the second
choice.
Despite the excellent regioselectivity accomplished by the addi-
tion of ZnI2, a variety of Zn salts were examined next (Table 2). The
reactions with ZnF2 and ZnCl2 were less regioselective and/or
Subsequently, different alkyl groups were examined (Table 3).
Me and Et groups were transferred successfully and the SN20 prod-
ucts 5b and 5c were obtained with 99% and 98% regioselectivity in
good yields, respectively (entries 1 and 2). Excellent regioselectiv-
ity was observed with the Bn, Ph(CH2)2, and Ph(CH2)3 groups to
produce 5d–f in 87–95% yields (entries 3–5), suggesting Ar groups
within the alkyl chain would be greatly acceptable to our reagent
system. Furthermore, a long alkyl chain (C16H33) was transferred
to the quaternary carbon center of 5g with 98% regioselectivity
(entry 5). Afterward, the cyclohexyl group (Cy) was selected to
study a steric factor, still achieving 92% regioselectivity for 5h (en-
try 7). In contrast, introduction of the t-Bu group proceeded less
regioselectively to produce a mixture of 5i, the regioisomer 6i,
and unidentified side products probably due to the increased steric
hindrance and the stronger basicity of the t-butylcopper species.
Next, substitution of cyclic picolinate 28e was studied as a typ-
ical example of cyclic substrates (Scheme 2). Reactions with the Bu
Table 2
Examination of various Zn salts
Bu2CuMgBr (1.5 equiv), ZnX2 (1.5 equiv)
5a + 6a + 7
1
THF, –18 oC, 1–2 h
Entry
X
5a:6a:7:1a
5a:6a
1
2
3
4
5
6
7
F
Cl
Br
PhCO2
AcO
TsO
CF3SO3
35:65:0:0
40:7:3:50
78:6:5:11
96:4:0:0
88:12:0:0
91:5:0:4
35:65
85:15
93:7
96:4
88:12
95:5
40:58:2:0
41:59
a
Determined by 1H NMR analysis of unpurified reaction mixtures.

C. Feng et al. / Tetrahedron Letters 54 (2013) 4629–4632
4631
R2CuMgBr (1.5equiv)
ZnI2 (1.5 equiv)
geometry of the olefin, which would be a synthetic convenience for
its application.
OCOPy
R
In conclusion, ZnI2-assisted substitution of
c,c-disubstituted
THF 40 oC, 1–2 h
, –
Et
Et
secondary allylic picolinates with (alkyl)2CuMgBr derived from al-
kyl-MgBr and CuBrꢀMe2S was established to be a convenient meth-
od to construct chiral quaternary carbon centers highly efficiently,
and the protocol was applied to optically active picolinates to con-
firm excellent CT. Notably, the absolute configuration of the chiral
quaternary carbon could be switched by changing the geometry of
the olefin in the picolinates. This alternation as well as easy avail-
ability of PyCO2H and alkyl-MgBr would be advantages of the pres-
ent method for synthetic application. Investigation for the
synthesis of natural products is currently going on and will be re-
ported in the near future.
R = Bu, 8a, rs 99%, 79% yield
2
rs
R = Cy, 8b, 97%, 81% yield
Scheme 2. Allylic substitution of cyclic picolinate 2.
and Cy copper reagents afforded 8a5b and 8b with 99 and 97% reg-
ioselectivity (rs), which are in similar levels to those observed for
acyclic substrates presented in Tables 1 and 3.
Encouraged by the above satisfactory results, we turned our
attention to subject optically active picolinates 3, (E)-4 and (Z)-4
to the above conditions to create asymmetric quaternary carbon
centers. As described in Table 4, reaction of 3 (98% ee) with
Bu2CuMgBr furnished the SN20 product 9a with 83% regioselectivi-
ty, whereas 97% CT11 was elucidated (entry 1). On the other hand,
addition of ZnI2 in 0.5 equiv and 1.5 equiv raised regioselectivity to
>99%, while CT was retained at high levels, respectively (entries 2
and 3). These results contrast sharply with the low reactivity of the
phenylcopper reagents (generated from 3 equiv of PhMgBr and
1.5 equiv of Cu(acac)2) in the reaction with 3,8e showing the high
reactivity of the alkylcopper species. The absolute configuration
Typical procedure for the construction of a chiral quaternary car-
bon (Table 4, entry 3): To
a suspension of anhydrous ZnI2
(32.5 mg, 0.102 mmol) and CuBrꢀMe2S (21.1 mg, 0.103 mmol) in
THF (1 mL) was added BuMgBr (0.25 mL, 0.87 M in THF,
0.218 mmol). After being stirred at 0 °C for 30 min, the mixture
was cooled to –40 °C.
A solution of picolinate 3 (32.1 mg,
0.0681 mmol, 98% ee) in THF (1 mL) was added to the above reac-
tion mixture at –40 °C. The reaction mixture was allowed to warm
to ꢁ15 °C over 1 h and diluted with saturated NH4Cl. The resulting
mixture was extracted by hexane three times. The combined ex-
tracts were washed with brine and dried over MgSO4. The solvents
were evaporated and the remaining residue was purified by chro-
of 9a was proven to be S by comparing the [
a]
value of 9a (½a 2D3
ꢂ
D
+5.4 (c 0.40, CHCl3)) with that reported for the S isomer of 98%
matography (hexane) to furnish 9a (25.4 mg, 92% yield): ½a D23
ꢂ
+5.4
ee (½a 2D7
ꢂ
+3.2 (c 0.50, CHCl3),5b establishing the anti SN20 pathway
(c 0.40, CHCl3); IR (neat) 1613, 1514, 1249, 837, 776 cm–1; 1H NMR
(400 MHz, CDCl3) d 0.06 (s, 6H), 0.86 (t, J = 8 Hz, 3H), 0.90 (s, 9H),
1.00 (s, 3H), 1.10ꢁ1.19 (m, 2H), 1.20ꢁ1.28 (m, 2H), 1.32ꢁ1.39
(m, 2H), 3.17 (d, J = 9 Hz, 1H), 3.19 (d, J = 9 Hz, 1H), 3.80 (s, 3H),
4.16 (dd, J = 5, 1 Hz, 2H), 4.42 (s, 2H), 5.47 (dt, J = 16, 5 Hz, 1H),
5.60 (dm, J = 16 Hz, 1H), 6.86 (dm, J = 8 Hz, 2H), 7.24 (dm,
J = 8 Hz, 2H); 13C NMR (100 MHz, CDCl3) d ꢁ4.9 (+), 14.2 (+), 18.5
(ꢁ), 21.7 (+), 23.6 (ꢁ), 26.1 (+), 26.2 (ꢁ), 37.8 (ꢁ), 40.0 (ꢁ), 55.3
(+), 64.6 (ꢁ), 73.0 (ꢁ), 77.9 (ꢁ), 113.7 (+), 127.3 (+), 129.0 (+),
131.1 (ꢁ), 137.4 (+), 159.1 (ꢁ). HRMS (FAB) calcd for C24H41O3Si
[(MꢁH)+] 405.2825, found 405.2829. The 1H and 13C NMR spectra
for 9a unambiguously. The absolute stereochemistry of the other
products was deduced by analogy based on the anti SN20 mecha-
nism. Other zinc salts examined in entries 4–6 gave 9a with excel-
lent regioselectivity and CT, whereas somewhat low yields
observed with Zn(OCOPh)2 and Zn(OTs)2 were due to generation
of the corresponding alcohol. Cyclohexyl (Cy) and PhCH2CH2
groups examined next furnished the anti SN20 products 9b and 9c
with high selectivity11 in good yields (entries 7 and 8). Further-
more, allylic substitution of (E)- and (Z)-4 furnished the stereoiso-
mers (S)- and (R)-10, respectively11 (entries 9 and 10), illustrating
that the absolute configuration of the product is controlled by the
Table 4
Allylic substitution of optically active picolinates with alkylcopper reagentsa
Entry
Substrate
Organocopper reagents (equiv)
ZnX2
Product
Regioselectivityb
%
CTc
%
Yieldd
%
1
2
3
4
5
6
3 (98% ee)
Bu2CuMgBr (1.5)
Bu2CuMgBr (1.5)
Bu2CuMgBr (1.5)
Bu2CuMgBr (1.5)
Bu2CuMgBr (1.5)
Bu2CuMgBr (1.5)
—
9a
9a
9a
9a
9a
9a
83
97
99
>99
99
>99
>99
77
85
92
89
78
74
3
3
3
3
3
Znl2(0.5)
Znl2(1.5)
ZnBr2(1.5)
Zn(PhCOO)2 (1.5)
Zn(OTs)2 (1.5)
>99
>99
>99
99
98
7
8
3
3
Cy2CuMgBr (1.5)
Znl2(1.5)
Znl2(1.5)
94
98
82
86
(PhCH2CH2)2CuMgBr (1.5)
>99
>99
9
(PhCH2CH2)2CuMgBr (1.5)
(PhCH2CH2)2CuMgBr (1.5)
Znl2(1.5)
Znl2(1.5)
98
97
>99
98
90
82
10
a
b
c
Reaction conditions: THF, –40 °C, 1–2 h.
Determined by 1H NMR analysis of the unpurified reaction mixtures.
Defined as (% ee of product) ꢃ 100/(% ee of substrate). The enantiomeric purities were determined by chiral HPLC analysis of the corresponding alcohols after removal of
the TBS group (entries 1–8) and of the products as such (entries 9 and 10).
d
Isolated yield.

4632
C. Feng et al. / Tetrahedron Letters 54 (2013) 4629–4632
K.; Hoveyda, A. H. Angew. Chem., Int. Ed. 2010, 49, 8370; (e) Sonawane, R. P.;
were identical with those and the [a]D value is close to that of the S
enantiomer (½a 2D7
ꢂ
+3.2 (c 0.50, CHCl3)) reported.5b
Jheengut, V.; Rabalakos, C.; Larouche-Gauthier, R.; Scott, H. K.; Aggarwal, V. K.
Angew. Chem., Int. Ed. 2011, 50, 3760; (f) Schnermann, M. J.; Overman, L. E.
Angew. Chem., Int. Ed. 2012, 51, 9576; (g) Schnermann, M. J.; Untiedt, N. L.;
Jiménez-Osés, G.; Houk, K. N.; Overman, L. E. Angew. Chem., Int. Ed. 2012, 51,
9581.
Derivation to the alcohol for chiral HPLC analysis: The above
product 9a (25.4 mg, 0.062 mmol) was dissolved in THF (3.0 mL)
and treated with TBAF (0.13 mL, 1.0 M in THF, 0.130 mmol) at rt
for 1 h to afford the corresponding alcohol (16.1 mg, 98% ee,
4. Lumbroso, A.; Cooke, M. L.; Breit, B. Angew. Chem., Int. Ed. 2013, 52, 1890.
5. (a) Breit, B.; Demel, P.; Studte, C. Angew. Chem., Int. Ed. 2004, 43, 3786; (b) Breit,
B.; Demel, P.; Grauer, D.; Studte, C. Chem. Asian J. 2006, 1, 586.
6. (a) Harrington-Frost, N.; Leuser, H.; Calaza, M. I.; Kneisel, F. F.; Knochel, P. Org.
Lett. 2003, 5, 2111; (b) Leuser, H.; Perrone, S.; Liron, F.; Kneisel, F. F.; Knochel, P.
Angew. Chem., Int. Ed. 2005, 44, 4627; (c) Perrone, S.; Knochel, P. Org. Lett. 2007,
9, 1041.
100% CT, 88% yield): ½a D24
ꢂ
+9.3 (c 0.20, CHCl3); IR (neat) 3398,
1612, 1513, 1248, 1092 cmꢁ1
;
1H NMR (400 MHz, CDCl3) d 0.87
(t, J = 7 Hz, 3H), 1.00 (s, 3H), 1.08–1.18 (m, 2H), 1.20–1.32 (m,
2H), 1.32ꢁ1.39 (m, 2H), 1.62 (br s, 1H), 3.19 (s, 2H), 3.80 (s, 3H),
4.11 (d, J = 5 Hz, 2H), 4.43 (s, 2H), 5.57 (dt, J = 16, 5 Hz, 1H), 5.66
(d, J = 16 Hz, 1H), 6.87 (d, J = 9 Hz, 2H), 7.24 (d, J = 9 Hz, 2H); 13C
NMR (100 MHz, CDCl3) d 14.2 (+), 21.6 (+), 23.5 (ꢁ), 26.2 (ꢁ),
37.7 (ꢁ), 40.1 (ꢁ), 55.4 (+), 64.3 (ꢁ), 73.0 (ꢁ), 77.7 (ꢁ), 113.8 (+),
127.0 (+), 129.1 (+), 130.9 (ꢁ), 139.4 (+), 159.2 (ꢁ). HRMS (FAB)
calcd for C16H28O3Na [(M+Na)+] 315.1936, found 315.1936. The
enantiomeric purity was determined by chiral HPLC analysis: Chi-
ralcel AS-H, hexane/i-PrOH = 97/3, 0.500 mL/min, 30 °C, tR/
min = 26.4 (R-isomer), 31.8 (S-isomer).
7. Spino, C.; Beaulieu, C. Angew. Chem., Int. Ed. 2000, 39, 1930.
8. (a) Kiyotsuka, Y.; Acharya, H. P.; Katayama, Y.; Hyodo, T.; Kobayashi, Y. Org.
Lett. 2008, 10, 1719; (b) Kiyotsuka, Y.; Kobayashi, Y. Tetrahedron Lett. 2008, 49,
7256; (c) Kiyotsuka, Y.; Katayama, Y.; Acharya, H. P.; Hyodo, T.; Kobayashi, Y. J.
Org. Chem. 1939, 2009, 74; (d) Kaneko, Y.; Kiyotsuka, Y.; Acharya, H. P.;
Kobayashi, Y. Chem. Commun. 2010, 5482; (e) Chao, F.; Kobayashi, Y. J. Org.
Chem. 2013, 78, 3755.
9. (a) House, H. O.; Respess, W. L.; Whitesides, G. M. J. Org. Chem. 1966, 31, 3128;
(b) Fujii, N.; Nakai, K.; Habashita, H.; Yoshizawa, H.; Ibuka, T.; Garrido, F.;
Mann, A.; Chounan, Y.; Yamamoto, Y. Tetrahedron Lett. 1993, 34, 4227.
10. Regioisomer 6a was prepared as a 1:1 mixture of 6a and 5a by a following
transformation:
c
d
a,b
5a + 6a
(1:1)
Acknowledgments
45%
OCOPy
44%
58%
OH
Ph
Ph
Ph
This work was supported by a Grant-in-Aid for Scientific Re-
search from the Ministry of Education, Science, Sports, and Culture,
Japan.
Conditions: (a) BuLi (1.5 equiv) then acetone (2.0 equiv), THF, ꢁ78 °C, 2 h; (b)
Red-Al (2.0 equiv), THF, 0 oC, 1 h; (c) DCC (1.3 equiv), DMAP (0.5 equiv),
PyCO2H (1.1 equiv), CH2Cl2, rt, overnight; (d) BuMgBr (3.0 equiv), CuBrꢀMe2S
(1.5 equiv), THF, 0 oC, 1 h.
11. Enantiomeric excesses (ee) of products 9a–c for calculation of CT were
determined by chiral HPLC analysis of the corresponding alcohols, which were
synthesized by desilylation with TBAF, while (S)- and (R)-10 were subjected to
chiral HPLC analysis. Alcohol from 9a: see the typical procedure. Alcohol from
Supplementary data
9b (92%): ½a 2D3
ꢂ
+14 (c 0.20, CHCl3). IR (neat) 3416, 1612, 1513, 1248, 1087 cm–1
.
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2013.
06.046.
1H NMR (400 MHz, CDCl3) d 0.80ꢁ1.34 (m, 5H), 0.95 (s, 3H), 1.42 (tt, J = 12,
2.5 Hz, 1H), 1.48ꢁ1.78 (m, 6H), 3.22 (d, J = 9 Hz, 1H), 3.26 (d, J = 9 Hz, 1H), 3.81
(s, 3H), 4.12 (d, J = 6 Hz, 2H), 4.41 (s, 2H), 5.56 (dt, J = 16, 6 Hz, 1H), 5.71 (d,
J = 16 Hz, 1H), 6.87 (d, J = 8 Hz, 2H), 7.23 (d, J = 8 Hz, 2H); 13C NMR (100 MHz,
CDCl3) d 18.4 (+), 26.8 (ꢁ), 27.09 (ꢁ), 27.13 (ꢁ), 27.3 (ꢁ), 27.6 (ꢁ), 42.7 (ꢁ),
43.1 (+), 55.4 (+), 64.4 (ꢁ), 73.0 (ꢁ), 76.3 (ꢁ), 113.8 (+), 127.4 (+), 129.1 (+),
130.9 (ꢁ), 138.9 (+), 159.2 (ꢁ). HRMS (EI) calcd for C20H30O3 [M+] 318.2195,
found 318.2199. The enantiomeric purity was determined by chiral HPLC
analysis: Chiralcel AS-H, hexane/i-PrOH = 97/3, 0.500 mL/min, 30 °C, tR/
min = 20.3 (R-isomer), 23.9 (S-isomer). Alcohol from 9c (87%): 1H NMR
References and notes
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(400 MHz, CDCl3)
d
1.10 (s, 3H), 1.46 (br s, 1H), 1.63ꢁ1.78 (m, 2H),
2.42ꢁ2.56 (m, 2H), 3.24 (s, 2H), 3.80 (s, 3H), 4.12 (d, J = 5 Hz, 2H), 4.44 (s,
2H), 5.63 (dt, J = 16, 5 Hz, 1H), 5.70 (d, J = 16 Hz, 1H), 6.87 (d, J = 8.5 Hz, 2H),
7.11ꢁ7.30 (m, 7H); 13C NMR (100 MHz, CDCl3) d 21.6 (+), 30.6 (ꢁ), 40.0 (ꢁ),
40.3 (ꢁ), 55.3 (+), 64.1 (ꢁ), 73.1 (ꢁ), 77.5 (ꢁ), 113.8 (+), 125.6 (+), 127.5 (+),
128.3 (+), 128.4 (+), 129.2 (+), 130.7 (ꢁ), 138.6 (+), 143.1 (ꢁ), 159.1 (ꢁ). The
enantiomeric purity was determined by chiral HPLC analysis: Chiralcel AS-H,
hexane/i-PrOH = 97/3, 0.500 mL/min, 30 °C, tR/min = 31.4 (R-isomer), 34.2 (S-
isomer). (S)- and (R)-10: The enantiomeric purity was determined by chiral
HPLC analysis: Chiralcel OJ-H, hexane/i-PrOH = 99.8/0.2, 0.300 mL/min, 35 °C,
tR/min = 15.9 (S-isomer), 16.7 (R-isomer).