Palladium-catalyzed asymmetric ring expansion of allenylcyclobutanols: An asymmetric Wagner-Meerwein shift

Article abstract of DOI:10.1021/ja0602501

In this study, we developed a palladium-catalyzed atom economic asymmetric Wagner-Meerwein shift of allenylcyclobutanol substrates. It is an excellent method for creating functionalized cyclopentanones with an α-chiral O-tertiary center by ring expansion

Full text of DOI:10.1021/ja0602501

Palladium-Catalyzed Asymmetric Ring Expansion of Allenylcyclobutanols:
An Asymmetric Wagner-Meerwein Shift
Barry M. Trost,* Jia Xie
Department of Chemistry, Stanford University, Stanford, California 94305-8080
bmtrost@stanford.edu
Supporting Information
Part A: Experimental Section
Experimental
General
All reactions were carried out under an atmosphere of nitrogen or argon in
oven-dried glassware with magnetic stirring, unless otherwise indicated. Some
solvents were freshly purified by column before use: acetonitrile, methylene chloride,
toluene, benzene, triethylamine, dimethylformamide, tetrahydrofuran and pyridine
and diethyl ether. Methanol was distilled from magnesium methoxide. Solvents for
1
Pd-catalyzed reactions were degassed by freeze-thaw techniques under vaccum .
Tris-(dibenzylideneacetone)palladium(0) monochloroform complex, Pd
2
dba
3 3
•CHCl
2
was prepared by the procedure of Ibers . Ligands L1, L2, L3, and L4 were prepared
3,4
by literature procedures . All other reagents were used as obtained unless otherwise
noted.
Flash Chromatography was performed with EM Science silica gel
(
0
0.040-0.063µm grade). Analytical thin-layer chromatography was performed with
.2 mm coated commercial silica gel plates (E. Merck, DC-Plasrikfolien, kieselgel 60
F254). Melting points were obtained on a Thomas-Hoover apparatus in open capillary
tubes and are uncorrected. Kugelrohr distillations were performed on a Büchi
GKR-50 glass tube oven.
Proton nuclear magnetic resonance (1H-NMR) data were acquired at 300 MHz on
a Varian GEM-300, Varian mercury 400 (400 MHz) or on a Varian Unity Inova-500
(
500 MHz) spectrometer.. Chemical shifts are reported in delta (δ) units, in parts per
million (ppm) downfield from tetramethylsilane, of in ppm relative to the singlet at
.26 ppm from chloroform-d. Splitting patterns are designated as s, singlet; d, doublet;
t, triplet; q, quartet; m, multiplet; br, broad. Carbon-13 nuclear magnetic resonance
13C-NMR) data were acquired at 75 MHz on a Varian GEM-300, 100 MHz on a
7
(
Varian mercury 400 and at 125 MHz on a Varian Unity Inova-500 spectrometer.
Chemical shifts are reported in ppm relative to the center line of a triplet at 77.0 ppm
for choroform-d.
Infrared (IR) data were recorded as films on sodium chloride plates or a
potassium bromide (KBr) pellets on a Perkin-Elmer Paragon 500 FT-IR spectrometer.
Absorbance frequencies are reported in reciprocal centimeters (cm-1). High resolution
mass spectral data (HRMS) were obtained from Mass Spectrometry Resource, School
of S2 Pharmacy, University of California-San Francisco, on a Kratos MS9
spectrometer at an ionizing current of 98 mA and an ionizing voltage of 70 eV.
S１

Elemental analyses (Anal.) were performed by M.-H.-W. Laboratories of Pheonix,
AZ. Chiral GC analyses were performed on a HP 6890 series GC system using a
Cyclosil B chiral column. GC analyses were performed on a HP 6850 series GC
system using a Agilent Technologies HP-1 GC column (30 m length, 0.32 mm I.D.,
0
.25 µm film). Chiral HPLC analyses were performed on a Themo Separation
Products Spectra Series P-100 or 200 and UV100 (254 nm) using Chiralcel® columns
OD, OB-H, OJ, AD, As, or OC) eluting with heptane / iso-propanol mixtures
(
indicated. Optical rotations were measured on a Jasco DIP-1000 digital polarimeter
using 5 cm cells and the sodium D line (589 nm) at ambient temperature in the solvent
and concentration indicated.
General procedure for preparation of propargyl ether:
OBn
5
Prop-2-ynyloxymethyl-benzene (1a)
Method A : To a suspension of KOH(16.8g, 0.30mol) in 100ml DMSO was
o
added 5.4ml (0.10mol, 1.0 eq.) propargyl alcohol at 0 C. After stirring for 10 min,
o
benzyl bromide (11.9ml, 0.10mol) was added at 0 C. Stirring was continued for 3 h at
room temperature. The resulting brown suspension was diluted with 200ml water and
was extracted with diethyl ether (3*100ml). The combined organic layer was washed
with water (4*60ml), brine, dried over MgSO , filtered and concentrated in vacuo.
4
Purification of the yellowish, oily liquid by flash chromatography (2% diethyl ether in
petroleum ether, silica gel) gave 1a (14.0g, 88%) as a colorless, oily liquid.
f
R (10% ether / pet. ether)): 0.70. IR (neat): 3294, 2924, 2854, 1496, 1454, 1355,
-
1 1
1
4
090, 1078, 1028, 739, 697 cm . H NMR (300 MHz, CDCl
3
): δ 7.35 – 7.20 (m, 5H),
1
3
.62 (s, 2H), 4.18(d, J = 2.1 Hz, 2H), 2.48 (dd, J = 2.4 Hz, 1H). C NMR (75 MHz,
CDCl
3
): δ 132.5, 123.7, 123.3, 123.1, 74.9, 69.8, 66.8, 52.3.”
O
6
4
-Prop-2-ynyloxy-but-1-ene (7a)
Method B : To a suspension of KOH (8.42g, 150mmol) in 100ml DMSO was
o
added 3-buten-1-ol (4.30ml, 50mmol) at 0 C. After stirring for 10 min, propargyl
o
bromide (5.55ml, 80% wt. in toluene,50mmol) was added at 0 C. Stirring was
continued for 3 h at room temperature. The resulting brown suspension was diluted
with 200ml water and was extracted with diethyl ether (3*100ml). The combined
organic layer was washed with water (4*60ml), brine, dried over MgSO , filtered and
4
concentrated in vacuo. Purification of the yellowish, oily liquid by flash
chromatography (2% diethyl ether in petroleum ether, silica gel) gave 2a (4.0g, 88%)
as a yellowish, oily liquid.
f
R (10% ether / pet. ether): 0.53. IR (neat): 3300, 3079, 2916, 2860, 1643, 1443,
-1 1
1
3
357, 1276, 1102, 996, 916, 633 cm . H NMR (500 MHz, CDCl ): δ 5.80 ~ 5.71 (m,
1
H), 5.07 ~ 4.97 (m, 2H), 4.15 (d, J = 2.4 Hz, 2H), 3.58 (t, J = 6.6 Hz, 2H), 2.44 (t, J
S２

1
3
=
1 2 3
2.4 Hz, 1H). 2.36 (tq, J = 6.6 Hz, J = 1.4 Hz, 2H). C NMR (125 MHz, CDCl ):
δ 134.8, 116.4, 79.7, 74.2, 69.1, 57.9, 33.8.
O
5-Prop-2-ynyloxy-pent-1-ene (9a)
Propargyl ether 3a was prepared according to Method B in general procedure
starting from 5-hexen-1-ol (4.1ml, 40mmol). Yield 4.55g (92%)
R (10% ether / pet. ether): 0.63. IR (neat): 3301, 3078, 2940, 2854, 1641, 1608,
f
-1 1
1
443, 1358, 1104, 1042, 993, 914 cm . H NMR (500 MHz, CDCl ): δ 6.06 ~ 5.98
3
(
(
m, 1H), 5.26 ~ 5.16 (m, 2H), 4.33 (d, J = 2.5 Hz, 2H), 3.72 (t, J = 6.5 Hz, 2H), 2.62
t, J = 2.5 Hz, 1H), 2.36 ~ 2.31 (m, 2H), 1.92 ~ 1.87 (m, 2H). C NMR (125 MHz,
1
3
CDCl
3
): δ 138.0, 114.8, 79.9, 74.0, 69.4, 57.9, 30.1, 28.6
O
7
5
-Prop-2-ynyloxy-pent-2-yne (11a)
Propargyl ether 4a was prepared according Method B in general procedure
starting from 3-pentyn-1-ol (3.7ml, 40mmol).. Yield 4.2g (88%)
(10% ether / pet. ether): 0.53. IR (neat): 3288, 2921, 2866, 2116, 1442, 1358,
R
f
-1 1
1
262, 1223, 1102, 1030, 1007, 952, 912, 816cm . H NMR (300 MHz, CDCl
3
): δ
4
.11(m, 2H), 3.55 ~ 3.51 (m, 2H), 2.40 (m, 1H), 2.38 ~ 2.33 (m, 2H), 1.70 (m, 3H).
C NMR (75 MHz, CDCl ): δ 79.4, 76.6, 75.4, 74.4, 68.3, 57.9, 19.7, 3.28.
3
1
3
General Procedure for preparation of oxygen substituted allenes
OBn
5
Propa-1,2-dienyloxymethyl-benzene (1b)
t
At room temperature, 4.3g (38.3mmol) KO Bu was added into the solution of 22g
(
130mmol) benzyl-propargyl ether in 10ml THF. The suspension was stirred at room
temperature for 3 hours, then filtered through a celite pad and was washed with 50ml
Et O. Combined solution was concentrated in vacuo and purified by flash
chromatography (0.5~0.8% diethyl ether in petroleum ether with 0.5% Et N, silica gel
before running column) to afford 1b as a light yellowish,
2
3
was washed with 1% NEt
oily liquid (18g, 82%).
3
f
R (5% ether / pet. ether): 0.84. IR (neat): 3034, 2925, 2868, 1953, 1726, 1454,
-
1 1
1
7
442, 1349, 1190, 1043, 893, 737, 698cm . H NMR (300 MHz, CDCl
3
): δ 7.35 ~
1
3
.20 (m, 5H), 6.85 (dd, J = 6.3 Hz, 1H), 5.48 (d, J = 6.1 Hz, 2H), 4.62 (s, 2H). C
NMR (75 MHz, CDCl
8.1, 24.8, 23.9, 17.0.
3
): δ 132.0, 128.2, 123.5, 123.3, 123.1, 118.3, 101.1, 81.8, 66.1,
4
S３

OPMB
8
1
-Methoxy-4-propa-1,2-dienyloxymethyl-benzene (3b)
Allene 2b was prepared according to the general procedure for allene preparation
starting from 1-methoxy-4-prop-2-ynyloxymethyl-benzene (4.4g, 25mmol). Yield
3
.5g (80%).
R (10% ether / pet. ether): 0.80. IR (neat): 3039, 3002, 2959, 2837, 1953, 1614,
586, 1515, 1464, 1443, 1377, 1350, 1302, 1250, 1174, 1036, 892, 858, 822, 673cm .
f
-1
1
1
3
H NMR (400 MHz, CDCl ): δ 7.35 (d, J = 8.0 Hz, 2H), 6.95 (d, J = 7.8 Hz, 2H),
1
3
6
.92 ~ 6.89 (m, 1H), 5.56 ~ 5.54 (m, 2H), 4.62 (s, 2H), 3.83 (s, 3H). C NMR (100
3
MHz, CDCl ): δ 201.2, 159.2, 129.3, 129.1, 121.3, 113.6, 90.6, 70.2, 54.9.
O
n-C11H23
1
-Propa-1,2-dienyloxy-undecane (5b)
Allene 3b was prepared according to the general procedure for allene preparation
starting from 1-prop-2-ynyloxy-undecane (1.2g, 5.7mmol). Yield 0.85g (71%).
(5% ether / pet. ether): 0.90. IR (neat): 3042, 2925, 2855, 1953, 1467, 1446,
R
f
-1
1
1
379, 1351, 1262, 1202, 1104, 1044, 931, 888, 855, 795, 722cm . H NMR (400
MHz, CDCl ): δ 6.72 (t, J = 6.0 Hz, 1H), 5.42 (d, J = 6.0 Hz, 2H), 3.54 (t, J = 6.6 Hz,
H), 1.70 ~ 1.60 (m, 2H), 1.38 ~ 1.22 (m, 16H), 0.88 (t, J = 6.7 Hz, 3H). C NMR
100 MHz, CDCl ): δ 201.4, 121.6, 90.3, 68.9, 31.9, 29.62, 29.60, 29.56, 29.4, 29.3,
9.2, 26.0, 22.7, 14.1. HRMS (EI+) m/z calculated for C14H26O [M] : 210.1984,
3
1
3
2
(
2
3
+
found.210.1984
O
4
-Propa-1,2-dienyloxy-but-1-ene (7b)
Allene 4b was prepared according to the general procedure for allene preparation
starting from 2a (1,95g, 17.7mmol). Yield 1.40g (72%, 85% brsm).
(5% ether / pet. ether): 0.85. IR (neat): 3080, 2978, 2923, 2873, 1952, 1643, 1446,
R
1
f
-1
1
352, 1202, 1045, 956, 917, 891, 856cm . H NMR (400 MHz, CDCl
3
): δ 6.74 (t, J
=
6.0 Hz, 1H), 5.88 ~ 5.78 (m, 1H), 5.44 (d, J = 6.0 Hz, 2H), 5.15 ~ 5.05 (m, 2H),
1
3
3
.62 (t, J = 6.5 Hz, 2H), 2.44 ~ 2.38 (m, 2H). C NMR (100 MHz, CDCl
3
): δ 201.3,
1
34.7, 121.5, 116.7, 90.6, 67.8, 33.5. EA Anal. Calcd. for C 10O: C, 76.33; H, 9.15;
7
H
Found: C, 76.12; H, 8.93.
O
5
-Propa-1,2-dienyloxy-pent-1-ene (9b)
Allene 5b was prepared according to the general procedure for allene preparation
starting from 3a (2.48g, 20 mmol). Yield 2.0g (81%)
(10% ether / pet. ether): 0.90. IR (neat): 3079, 2977, 2941, 2873, 1953, 1642,
R
f
-
1
1
1
3
446, 1351, 1203, 1046, 994, 914, 890, 857cm . H NMR (400 MHz, CDCl ): δ
S４

6
2
.72 (t, J = 6.0 Hz, 1H), 5.88 ~ 5.76 (m, 1H), 5.41 (d, J = 6.0 Hz, 2H), 5.06 ~ 4.95 (m,
1
3
H), 3.56 (t, J = 6.5 Hz, 2H), 2.16 ~ 2.10 (m, 2H), 1.77~1.70 (m, 2H). C NMR (100
): δ 201.4, 137.8, 121.5, 114.8, 90.3, 67.9, 30.1, 28.3. LRMS (ESI+) m/z
MHz, CDCl
3
+
+
18 2
calculated for C12H O [M] : 124.1 found [M+Na] : 147.0.
O
5
-Propa-1,2-dienyloxy-pent-2-yne (11b)
Allene 6b was prepared according to the general procedure for allene preparation
starting from 4a (2.80g, 22.9 mmol). Yield 2.0g (71%)
R (10% ether / pet. ether): 0.82. IR (neat): 3044, 2976, 2921, 2878, 1952, 1468,
f
-1 1
1
446, 1352, 1200, 1106, 1048, 893, 856cm . H NMR (500 MHz, CDCl
3
): δ 6.75 (t,
J = 6.0 Hz, 1H), 5.46 (d, J = 6.0 Hz, 2H), 3.64 (t, J = 7.0 Hz, 2H), 2.50 ~ 2.47 (m, 2H),
1
3
1
7
.79 (t, J = 2.5 Hz, 3H). C NMR (125 MHz, CDCl ): δ 200.9, 121.3, 90.9, 76.9,
5.2, 67.1, 19.4, 3.5.
3
General Procedure for preparation of Substituted cyclobutanones
Zinc catalyzed ketene [2+2] reaction followed by zinc catalyzed dehalogenation
9
reduction.
Cl
O
Cl
Ph
Ph
1
0
2
,2-Dichloro-3,3-diphenyl-cyclobutanone (13a)
Cyclobutanone 1c was prepared according to the general procedure for
preparation of substituted cyclobutanones staring fromethene-1,1-diyldibenzene
9
(
5.41g, 30mmol), activated Zn (4.9g, 75mmol), trichloroacetic chloride (6.7ml,
6
8
0mmol) and POCl
6 C.
3
(5.7ml, 60mmol).. Yield: 6.5g (74%) yellow solid. M.P. = 84 ~
o
-1 1
R
f
(10% ether in pet. ether): 0.50. IR (neat): cm . H NMR (500 MHz, CDCl
3
): δ
1
3
7
.40 ~ 7.32 (m, 6H), 7.25 ~ 7.23 (m, 4H), 4.06 (s, 2H). C NMR (125 MHz, CDCl ):
3
δ 192.2, 140.9, 128.4, 128.3, 127.8, 92.5, 58.0, 54.3.
O
Ph
Ph
1
0
3
,3-Diphenyl-cyclobutanone(13b)
Cyclobutanone 13b was prepared according to the general procedure for
preparation of substituted cyclobutanones staring from 13a (5.50g, 18.9mmol). Yield:
o
3
.5g (83%) white solid. M.P. = 76 ~ 78 C.
(25% ether in pet. ether): 0.53. IR (neat): 3082, 3026, 2972, 2924, 1787, 1595,
580, 1493, 1449, 1375, 1239, 1127, 1084, 1022, 888, 777, 750, 710, 660, 584, cm .
R
f
-1
1
1
H NMR (500 MHz, CDCl
3
): δ 7.35 ~ 7.26 (m, 8H), 7.24 ~ 7.21 (m, 2H), 3.82 (s, 4H).
S５

1
3
3
C NMR (125 MHz, CDCl ): δ 205.6, 147.2, 130.3, 128.6, 126.6, 60.5, 42.0.
Cl
O
Cl
EtO C
2
EtO C
2
Diethyl-3,3'-(2,2-dichloro-3-oxocyclobutane-1,1-diyl)dipropanoate(19a)
Cyclobutanone 19a was prepared according to the general procedure for
preparation of substituted cyclobutanones staring from diethyl-4-methylene-
9
heptanedioate (4.10g, 18.0mmol), activated Zn (2.59g, 39.6mmol), trichloroacetic
chloride (4.0ml, 36.0mmol) and POCl
3
(3.4ml, 36.0mmol).Yield: 3.8g (62%).
R
f
(25% ether in pet. ether): 0.50. IR (neat): 2983, 2939, 1862, 1809, 1732, 1456,
-1 1
1
420, 1386, 1300, 1189, 1103, 1025, 986, 856, 757cm . H NMR (500 MHz, CDCl
3
):
δ 4.08 (q, J = 7.0Hz, 4H), 2.99 (s, 2H), 2.45 ~ 2.38 (m, 2H), 2.32 ~ 2.25 (m, 2H), 2.22
1
3
~
2.16 (m, 2H), 1.90 ~ 1.84 (m, 2H), 1.20 (t, J = 7.0Hz, 6H). C NMR (125 MHz,
CDCl ): δ 191.4, 172.0, 91.5, 60.7, 52.3, 47.0, 29.5, 28.6, 14.0. HRMS (EI+) m/z
calculated for C14
93.0370
3
+
+
+
H
2 5 2 5
20Cl O [M] : 338.0688, found [M+H] : 339.0770 [M-OC H ] :
2
O
EtO C
2
EtO C
2
Diethyl-3,3'-(3-oxocyclobutane-1,1-diyl)dipropanoate (19b)
Cyclobutanone 19b was prepared according to the general procedure for
preparation of substituted cyclobutanones staring from 19a (3.39g, 10.0mmol). Yield:
2
.2g (81%)
(50% ether in pet. ether): 0.50. IR (neat): 2978, 2928, 2862, 1779, 1728, 1452,
R
f
-1 1
1416, 1376, 1300, 1251, 1161, 1113, 1023, 943, 853, 782cm . H NMR (500 MHz,
CDCl ): δ 4.10 ~ 4.05 (m, 4H), 2.74 (s, 4H), 2.27 ~ 2.24 (m, 4H), 1.91 ~ 1.88 (m, 4H),
3
1
3
1
3
.23 ~ 1.19 (m, 6H). C NMR (125 MHz, CDCl
3
): δ 205.9, 172.8, 60.5, 56.3, 32.0,
+
1.5, 30.1, 14.0. HRMS (EI+) m/z calculated for C14
22 5
H O [M] : 270.1467, found
+
+
[M+H] : 271.1548, [M-Et] : 241.1072
O
BnO
11
3
-Benzyloxymethyl-cyclobutanone (23)
Cyclobutanone 23 was prepared according to the general procedure for
preparation of substituted cyclobutanones staring from allyloxymethyl-benzene (5.50g,
3
7.1mmol). Yield: 6.0g (58%) over two steps.
(25% ether in pet. ether): 0.40. IR (neat): 3031, 2857, 1782, 1496, 1454, 1383,
365, 1206, 1093, 1028, 738, 698cm . H NMR (500 MHz, CDCl ): δ 7.37 ~ 7.25 (m,
3
R
f
-
1 1
1
5
H), 4.55 (s, 2H), 3.58 (d, J = 6.5Hz, 2H), 3.15 ~ 3.08 (m, 2H), 2.90 ~ 2.84 (m, 2H),
S６

1
3
2
1
3
.72 ~ 2.64 (m, 1H). C NMR (125 MHz, CDCl ): δ 207.4, 137.9, 128.4, 127.7,
27.6, 73.1, 72.8, 49.9, 23.5.
General Procedure for Preparation of Allenylcyclobutanols
OH
OBn
1
-(1-Benzyloxy-propa-1,2-dienyl)-cyclobutanol (1)
To a stirred solution of benzyloxyallene 1b (1.46g, 10.0mmol) in THF (40ml)
was added dropwise a 2.70M solution of n-BuLi(3.70ml, 10.0mmol) in hexane at -78
o
o
C. After stirring was continued for 1h at -78 C, cyclobutanone (0.75ml, 10.0mmol)
o
was added dropwise to this solution and stirring was continued for 2h at -78 C and
then warmed up to r.t.. The reaction mixture was diluted with water and extracted
with diethyl ethyl. The combined extracts was washed with brine and dried over
Na SO , filtered and concentrated in vacuo. The residue was purified by flash
2
4
3
chromatography (15% diethyl ether in petroleum ether with 0.5% Et N, silica gel) to
o
give allenylcyclobutanol 1 (2.05g, 95%) as a white solid. M.P.: 43 ~ 45 C.
(25% ether / pet. ether): 0.30. IR (neat): 3420, 3089, 3062, 3035, 2981, 2936,
864, 1952, 1495, 1450, 1374, 1244, 1177, 1136, 1096, 1024, 980, 953, 885, 850, 809,
R
f
2
7
-
1 1
3
28, 693cm . H NMR (400 MHz, CDCl ): δ 7.35 ~ 7.20 (m, 5H), 5.58 (s, 2H), 4.67
(
1
s, 2H), 2.67 (s, 1H), 2.37 ~ 2.37(m, 2H), 2.22 ~ 2.14 (m, 2H), 1.82 ~ 1.73 (m, 1H),
1
3
.61 ~ 1.50 (m, 1H). C NMR (100 MHz, CDCl
3
): δ 196.3, 137.5, 135.8, 128.4,
1
27.9, 127.8, 92.6, 73.8, 71.0, 34.6, 12.8. HRMS (EI+) m/z calculated for C14
16 2
H O
+
[M] : 216.1150, found.216.1148.
OH
OPMB
1
-[1-(4-Methoxy-benzyloxy)-propa-1,2-dienyl]-cyclobutanol (3)
Allenylcyclobutanol 3 was prepared according to the general procedure for
preparation of allenylcyclobutanols starting from allene 3b (0.88g, 5.0mmol). Yield:
1
.0g (83%).
(25% ether /pet. ether): 0.20. IR (neat): 3428, 3035, 2942, 2869, 2837,
953, 1613, 1587, 1515, 1455, 1423, 1377, 1302, 1247, 1174, 1124, 1091, 1034, 979,
R
f
1
8
1
3
~
-
1 1
89, 822, 776, 709 cm . H NMR (400 MHz, CDCl
.6 Hz, 2H), 6.87 (dd, J = 6.8 Hz, J = 1.6 Hz, 2H), 5.58 (s, 2H), 4.60 (s, 2H), 3.80 (s,
H), 2.70 (s, 1H), 2.34 ~ 2.28 (m, 2H), 2.20 ~ 2.14 (m, 2H), 1.80 ~ 1.72 (m, 1H), 1.59
3 1 2
): δ 7.28 (dd, J = 7.0 Hz, J =
1
2
1
3
1.50 (m, 1H). C NMR (100 MHz, CDCl
3
): δ 196.2, 159.3, 135.5, 129.5, 129.4,
1
13.7, 92.2, 73.6, 70.6, 55.2, 34.4, 12.6. HRMS (EI+) m/z calculated for C15H O
18 2
+
[M] : 246.1256, found [M – OCH
3
]: 215.1073. EA Anal. Calcd. for C15
18 3
H O : C,
73.15; H, 7.37; Found: C, 73.33; H, 7.47.
S７

OH
O
n-C11H23
1
-(1-Undecyloxy-propa-1,2-dienyl)-cyclobutanol (5)
Allenylcyclobutanol 5 was prepared according to the general procedure for
preparation of allenylcyclobutanols starting from allene 5b (2.80g, 13.3mmol). Yield:
3
.0g (81%).
R (25% ether / pet. ether): 0.50. IR (neat): 3422, 2923, 2854, 1954, 1455, 1378,
f
-1 1
1
2
1
0
3
3
246, 1183, 1136, 1099, 957, 884, 723cm . H NMR (400 MHz, CDCl ): δ 5.54 (s,
H), 3.60 (t, J = 6.7 Hz, 2H), 2.60 (s, 1H), 2.33 ~ 2.26 (m, 2H), 2.21 ~ 2.13 (m, 2H),
.81 ~ 1.71 (m, 1H), 1.69 ~ 1.60 (m, 2H). 1.59 ~ 1.50 (m, 1H), 1.38 ~ 1.22 (m, 16H),
1
3
.88 (t, J = 6.7 Hz, 3H) C NMR (100 MHz, CDCl ): δ 196.2, 135.7, 91.7, 73.7, 69.3,
3
4.6, 29.9, 29.60, 29.58, 29.55, 29.4, 29.3, 29.1, 26.0, 22.7, 14.1, 12.6. HRMS (EI+)
+
m/z calculated for C18
H
32
O
2
[M] : 280.2402, found: 280.2402.
OH
O
2
1
-(1-But-3-enyloxy-propa-1,2-dienyl)-cyclobutanol (7)
Allenylcyclobutanol 7 was prepared according to the general procedure for
preparation of allenylcyclobutanols starting from allene 7b (0.30g, 2.72mmol). Yield
0
.36g (73%).
(25% ether / pet. ether): 0.33. IR (neat): 3418, 3080, 2975, 2944, 2869, 1955,
R
f
-1
1
1
744, 1657, 1452, 1376, 1246, 1182, 1135, 1100, 1035, 992, 891, 818cm .
): δ 5.86 ~ 5.77 (m, 1H), 5.55 (s, 2H), 5.13 ~ 5.04 (m, 2H),
.68 (t, J = 6.6 Hz, 2H), 3.05 (broad, 1H), 2.45 ~ 2.40 (m, 2H), 2.33 ~ 2.26 (m, 2H),
H
NMR (400 MHz, CDCl
3
2
3
1
3
.20 ~ 2.13 (m, 2H), 1.80 ~ 1.70 (m, 1H), 1.60 ~ 1.50 (m, 1H). C NMR (100 MHz,
+
3 16 2
CDCl ): δ HRMS (EI+) m/z calculated for C11H O [M] : 180.1150, found
+
[M-H] :179.1080
OH
O
3
1
-(1-Pent-4-enyloxy-propa-1,2-dienyl)-cyclobutanol (9)
Allenylcyclobutanol 9 was prepared according to the general procedure for
preparation of allenylcyclobutanols starting from allene 9b (0.62g, 5.0mmol). Yield
0
.75g (77%).
(25% ether / pet. ether): 0.40. IR (neat): 3446, 3078, 2976, 2942, 2874, 1953,
R
f
-1 1
1
641, 1450, 1355, 1246, 1182, 1135, 1098, 992, 956, 913, 886cm . H NMR (500
): δ 5.87 ~ 5.78 (m, 1H), 5.55 (s, 2H), 5.05 ~ 4.97 (m, 2H), 3.63 (t, J =
.5 Hz, 2H), 2.62 (s, 1H), 2.33 ~ 2.28 (m, 2H), 2.21 ~ 2.14 (m, 4H), 1.80 ~ 1.73 (m,
MHz, CDCl
3
6
3
9
1
3
H), 1.59 ~ 1.50 (m, 1H). C NMR (100 MHz, CDCl
3
): δ 196.0, 138.0, 135.6, 114.9,
1.9, 73.7, 68.5, 34.5, 30.2, 28.2, 12.6. HRMS (EI+) m/z calculated for C12
18 2
H O
+
+
[M] : 194.1307, found [M-C
2
H
4
] : 166.0992. LRMS (ESI+) m/z calculated for
S８

+
+
C
12
H
18
O
2
[M+Na] : 217.1 found [M+Na] : 217.1.
OH
O
2
1
-(1-Pent-3-ynyloxy-propa-1,2-dienyl)cyclobutanol (11)
Allenylcyclobutanol 11 was prepared according to the general procedure for
preparation of allenylcyclobutanols starting from allene 11b (0.45g, 3.68mmol).Yield
0
.65g (93%).
R (25% ether / pet. ether): 0.40. IR (neat): 3424, 2988, 2944, 2879, 1954, 1450,
f
-1 1
1
3
426, 1378, 1246, 1182, 1135, 1102, 994, 956, 889cm . H NMR (400 MHz, CDCl ):
δ 5.49 (s, 2H), 3.62 (t, J = 7.0 Hz, 2H), 2.90 (broad, 1H), 2.45 ~ 2.38 (m, 2H), 2.25 ~
2
~
6
.18 (m, 2H), 2.13 ~ 2.05 (m, 2H), 1.69 (t, J = 2.5 Hz, 3H), 1.74 ~ 1.64 (m, 1H), 1.49
1
3
1.40 (m, 1H). C NMR (100 MHz, CDCl ): δ 195.7, 135.1, 92.0, 76.9, 75.1, 73.4,
3
+
7.2, 34.3, 19.2, 12.5, 3.2. HRMS (EI+) m/z calculated for C H O [M] : 192.1150,
1
2
16
2
found: 192.1148.
OH
Ph
OBn
Ph
1
-(1-Benzyloxy-propa-1,2-dienyl)-3,3-diphenyl-cyclobutanol (13)
Allenylcyclobutanol 13 was prepared according to the general procedure for
preparation of allenylcyclobutanols starting from allene 1b (0.44g, 3.0mmol) and
o
cyclobutanone 13b (0.67g, 3.0mmol). Yield: 0.90g (81%). M.P.: 85 ~ 87 C.
f
R (25% ether / pet. ether): 0.28. IR (neat): 3549, 3414, 3061, 3020, 2928, 2936,
-
1 1
1
(
5
954, 1597, 1293, 1441, 1228, 1134, 1103, 1026, 974, 886, 741, 694cm . H NMR
500 MHz, CDCl ): δ 7.28 ~ 7.23 (m, 3H), 7.22 ~ 7.13 (m, 10H), 7.04 ~ 7.01 (m, 2H),
.15 (s, 2H), 4.53 (s, 2H), 3.34 (d, J = 13.3Hz, 2H), 2.98 (d, J = 13.3Hz, 2H), 2.68
3
1
3
(
broad, 1H). C NMR (125 MHz, CDCl
3
): δ197.0, 150.7, 147.7, 137.3, 135.2, 128.4,
1
28.3, 128.2, 127.9, 127.7, 127.7, 126.9, 126.7, 125.9, 92.6, 70.7, 69.9, 47.0, 42.7.
+
HRMS (EI+) m/z calculated for C H O [M] : 368.1776, found: 368.1784.
2
6
24
2
OH
Et
OBn
Et
1
-(1-Benzyloxy-propa-1,2-dienyl)-3,3-diethylcyclobutanol (15)
Allenylcyclobutanol 15 was prepared according to the general procedure for
preparation of allenylcyclobutanols starting from allene 1b (0.90g, 6.18mmol) and
3
,3-diethylcyclobutanone (0.78g, 6.18mmol). Yield: 1.0g (60%).
(25% ether / pet. ether): 0.40. IR (neat): 3448, 3065, 3033, 2962, 2934, 2875,
954, 1744, 1498, 1456, 1377, 1287, 1222, 1185, 1130, 1080, 1008, 887, 734,
R
f
1
6
2
-1 1
96cm . H NMR (400 MHz, CDCl ): δ 7.37 ~ 7.24 (m, 5H), 5.54 (s, 2H), 4.66 (s,
3
H), 2.54 (broad, 1H), 2.16 (dd, J
1 2 1
= 10.8Hz, J = 3.0Hz, 2H), 1.86 (dd, J = 10.8Hz,
J
2
= 3.0Hz, 2H), 1.56 (t, J = 6.5Hz, 2H), 1.37 (t, J = 6.5Hz, 2H), 0.76 (d, J = 6.5Hz,
S９

1
3
3
1
H), 0.69 (d, J = 6.5Hz, 3H). C NMR (125 MHz, CDCl
3
): δ 196.7, 137.4, 127.3,
28.3, 127.7, 127.6, 92.7, 70.8, 69.4, 43.2, 33.2, 30.9, 29.0, 8.1, 7.8. HRMS (EI+)
+
m/z calculated for C H O [M] : 272.1776, found [M – C H ]: 243.1391, LRMS
1
8
24
2
2
5
+
+
(
24 2
ESI+) [M+H] : 273.2, [M+Na] : 295.2. EA Anal. Calcd. for C18H O : C: 79.37, H:
8
.88, found: C: 79.60, H: 8.80
OH
OBn
2
-(1-Benzyloxy-propa-1,2-dienyl)-spiro[3.4]octan-2-ol (17)
Allenylcyclobutanol 17 was prepared according to the general procedure for
preparation of allenylcyclobutanols starting from allene 1b (0.85g, 5.80mmol) and
Spiro[3.4]octan-2-one (0.72g, 5.80mmol).Yield: 1.1g (70%).
R (25% ether / pet. ether): 0.40. IR (neat): 3448, 3065, 3033, 2962, 2934, 2875,
f
1
6
2
1
1
954, 1744, 1498, 1456, 1377, 1287, 1222, 1185, 1130, 1080, 1008, 887, 734,
-1 1
96cm . H NMR (400 MHz, CDCl ): δ 7.36 ~ 7.29 (m, 5H), 5.55 (s, 2H), 4.68 (s,
3
H), 2.55 (broad, 1H), 2.31 (m, 2H), 2.08 (m, 2H), 1.67 (t, J = 6.5Hz, 2H), 1.54 ~
1
3
.50 (m, 6H). C NMR (125 MHz, CDCl
3
): δ 196.8, 137.4, 136.6, 128.3, 127.8,
27.7, 92.7, 70.9, 69.8, 45.2, 41.1, 39.0, 37.4, 24.0, 23.6. HRMS (EI+) m/z calculated
+
22 2
for C18H O [M] : 270.1620, found: 270.1618
OH
OBn
EtO C
2
EtO C
2
Diethyl-3,3'-(3-(1-benzyloxy-propa-1,2-dienyl)-3-hydroxycyclobutane-1,1-diyl)di
propanoate (19)
Allenylcyclobutanol 19 was prepared according to the general procedure for
preparation of allenylcyclobutanols starting from allene 1b (0.90g, 6.18mmol) and
cyclobutanone 19b (0.78g, 6.18mmol).
f
R (50% ether / pet. ether): 0.25. IR (neat): 3497, 3065, 3032, 2979, 2933, 2872,
-
1
1
953, 1782, 1732, 1498, 1455, 1375, 1301, 1182, 1117, 1028, 892, 856, 737, 698 cm .
1
H NMR (500 MHz, CDCl
3
): δ7.37 ~ 7.27 (m, 5H), 5.59 (s, 2H), 4.66 (s, 2H), 4.14 ~
4
1
.09 (m, 4H), 2.63 (s, 1H), 2.24 ~ 2.20 (m, 4H), 2.15 ~ 2.12 (m, 2H), 1.93 (m, 2H),
1
3
.90 ~ 1.87 (m, 2H), 1.72 ~ 1.69 (m, 2H), 1.27 ~ 1.24 (m, 6H). C NMR (125 MHz,
): δ 196.3, 173.6, 137.1, 136.7, 128.3, 127.8, 127.7, 93.3, 70.9, 69.1, 60.4, 60.3,
3.1, 33.6, 32.0, 31.9, 29.4, 29.2, 14.2. HRMS (EI+) m/z calculated for C24
CDCl
4
3
32 6
H O
+
[M] : 416.2199, found [M – OC
2 5 32 6
H ]: 371.1846. EA Anal. Calcd. for C24H O : C:
6
9.21, H: 7.74, found: C: 68.97, H: 7.52
OH
BnO
OBn
3
-Benzyloxymethyl-1-(1-benzyloxy-propa-1,2-dienyl)-cyclobutanol (24)
S１０

Allenylcyclobutanol 24 was prepared according to the general procedure for
preparation of allenylcyclobutanols starting from allene 1b (1.50g, 10.3mmol) and
cyclobutanone 23 (1.92g, 10.0mmol). Total yield: 2.0g (58%, 87% BRSM) d.r.= 4.5:1
(
by NMR).
Major diastereomer 24a. R (50% ether / pet. ether): 0.53. IR (neat): 3448, 3065,
f
3
1
2
2
1
3
033, 2962, 2934, 2875, 1954, 1744, 1498, 1456, 1377, 1287, 1222, 1185, 1130, 1080,
-1 1
008, 887, 734, 696cm . H NMR (500 MHz, CDCl ): δ7.34 ~ 7.26 (m, 10H), 5.57 (s,
3
H), 4.67 (s, 2H), 4.51 (s, 2H), 3.47 (d, J = 6.5Hz, 2H), 2.98 (s, 1H), 2.54 ~ 2.50 (m,
1
3
3
H), 2.20 ~ 2.14 (m, 1H), 1.99 ~ 1.95 (m, 2H). C NMR (125 MHz, CDCl ): δ 196.1,
38.3, 137.3, 135.7, 128.3, 127.8, 127.7, 127.6, 127.5, 92.7, 74.5, 73.0, 70.9, 70.6,
+
8.0, 25.9. HRMS (EI+) m/z calculated for C H O [M] : 336.1725, found
2
2
24
3
+
+
[M-Bn(C H )] : 245.1184 [Bn(C H )] : 91.0552
7 7 7 7
Minor diastereomer 24b R
f
(50% ether / pet. ether): 0.45. IR (neat): 3448, 3065,
3
1
033, 2962, 2934, 2875, 1954, 1744, 1498, 1456, 1377, 1287, 1222, 1185, 1130, 1080,
-1 1
008, 887, 734, 696cm . H NMR (500 MHz, CDCl ): δ 7.35 ~ 7.26 (m, 10H), 5.51
3
(
s, 2H), 4.64 (s, 2H), 4.48 (s, 2H), 3.42 (d, J = 7.2Hz, 2H), 2.73 ~ 2.67 (m, 1H), 2.49
1
3
(s, 1H), 2.29 ~ 2.25 (m, 2H), 2.21 ~ 2.17 (m, 2H). C NMR (125 MHz, CDCl
3
): δ
96.3, 138.5, 137.3, 136.6, 128.4, 128.3, 127.8, 127.7, 127.6, 127.5, 93.2, 74.1, 72.9,
2.3, 70.9, 36.5, 26.4.
1
7
General procedure for palladium-catalyzed ring expansion reaction.
O
OBn
2
-Benzyloxy-2-vinyl-cyclopentanone (2)
5ml DCE (which was dried and free-pump-thaw) was added into the mixture of
2
.
2 3 3
Pd (dba) CHCl (65.8mg, 63.6µmol) and (R,R)-stilbene ligand L3 (150.3mg,
0
.191mmol) which were three times evacuated and flushed with argon. The mixture
was stirred under argon at room temperature for 15 minutes. Then it was cannulated
into the allenylcyclobutanol 1 (550mg, 2.54mmol) with 4Å MS which was three times
2
evacuated and flushed with argon followed by adding PhCO H (0.25ml, 1M in
CH Cl , 0.25mmol) and Et N (0.25ml, 1M in CH Cl , 0.25mmol) respectively via
2
2
3
2
2
o
syringe. After stirring under argon at 30 C for 12 hours, the mixture was filtered
through a Celite pad, concentrated and purified by direct flash chromatography (5%
diethyl ether in petroleum ether, silica gel) to give desired product 2 (530mg, 96%).
Racemic product was prepared with same procedure using racemic standard Trost
ligand L1.
f
R (25% ether / pet. ether): 0.50. IR (neat): 3085, 3058, 3022, 2958, 2913, 2877,
-
1
1
746, 1492, 1451, 1401, 1379, 1157, 1130, 1080, 1053, 931, 808, 736, 695, 659cm .
1
H NMR (500 MHz, CDCl
3
): δ 7.35 – 7.20 (m, 5H), 5.92 (dd, J = 17.5 Hz, 11 Hz,
1
H), 5.46 (dd, J = 11 Hz, 0.9 Hz 1H), 5.41 (dd, J = 17.5 Hz, 0.9 Hz 1H), 4.52 (d, J =
1
~
1.5 Hz, 1H), 4.48 (d, J = 11.5 Hz, 1H), 2.41~ 2.25(m, 2H), 2.24 ~ 2.18 (m, 1H), 2.14
2.02 (m, 2H), 1.88 ~ 1.79 (m, 1H). C NMR (125 MHz, CDCl ): δ 196.3, 137.5,
3
1
3
S１１

1
35.8, 128.4, 127.9, 127.8, 92.6, 73.8, 71.0, 34.6, 12.8 HRMS (EI+) m/z calculated
+
+
+
for C H O [M] : 216.1150, found [M-Bn(C H )] : 125.0607 [Bn(C H )] : 91.0552.
1
4
16
2
7
7
7
7
24.8
D
EA Anal. Calcd. for C14
68.58 (c = 1.70, CH Cl
chiral HPLC (Chiralpak OD, heptane:i-PrOH = 99.5:0.5, 1.0 mL/min, t = 17.22
H
16
O
2
: C, 77.75; H, 7.46; Found: C, 77.90; H, 7.30. [α]
=
-
2
2
), Enantiomeric excess was determined to be 92% ee by
1
2
min(major), t = 20.25 min).
O
OPMB
2
-(4-Methoxy-benzyloxy)-2-vinyl-cyclopentanone (4)
Cyclopentanone 4 was prepared according to the general procedure for ring
expansion at room temperature starting from allenylcyclobutanol 3 (495mg, 2.0
mmol). Yield 480mg (97%).
R (25% ether / pet. ether): 0.30. IR (neat): 2961, 2837, 1744, 1613, 1586, 1464,
f
-1 1
1
404, 1379, 1301, 1249, 1173, 1035, 934, 821, 766, 705, 661cm . H NMR (500
MHz, CDCl ): δ 7.23 (d, J = 8.6 Hz, 2H), 6.85 (d, J = 8.6 Hz, 2H), 5.92 (dd, J = 18
Hz, J =11 Hz, 1H), 5.45 (dd, J = 11 Hz, J = 1.0 Hz 1H), 5.41 (dd, J = 18 Hz, J
.0 Hz, 1H), 4.48 (d, J = 11 Hz, 1H), 4.40 (d, J = 11 Hz, 1H), 3.78 (s, 3H), 2.40~ 2.24
3
1
2
1
2
1
2
=
1
1
3
(
(
m, 2H), 2.21 ~ 2.16 (m, 1H), 2.12 ~ 2.00 (m, 2H), 1.89 ~ 1.77 (m, 1H). C NMR
125 MHz, CDCl ): δ 214.8, 159.0, 135.0, 130.6, 129.2, 119.4, 113.7, 83.5, 66.3, 55.2,
3
+
3
2
6.2, 34.9, 17.4. HRMS (EI+) m/z calculated for C15
H
18
O
3
[M] : 246.1256, found
2
2.1
46.1259. [α]
D
= - 49.57 (c = 0.80, CH Cl ), Enantiomeric excess was determined
2 2
to be 89% ee by chiral HPLC (Chiralpak AD, heptane:i-PrOH = 99:1, 1.0 mL/min, t1
=
15.18 min(major), t = 16.76 min).
2
O
n-C11H23
O
2
-Undecyloxy-2-vinylcyclopentanone (6)
Cyclopentanone 6 was prepared according to the general procedure for ring
expansion at room temperature starting from allenylcyclobutanol 5 (140mg,
0
.50mmol). Yield 140mg (100%).
R (25% ether in pet. ether): 0.75. IR (neat): 2924, 2855, 1744, 1466, 1406, 1379,
f
-
1 1
1
305, 1272, 1164, 1119, 1081, 994, 930, 812, 713, 663cm . H NMR (400 MHz,
): δ 5.80 (dd, J = 17.6 Hz, J =10.8 Hz, 1H), 5.37 (dd, J = 10.8 Hz, J = 1.0
Hz, 1H), 5.32 (dd, J = 17.6 Hz, J = 1.0 Hz, 1H), 3.41 ~ 3.30 (m, 2H), 2.38~ 2.19 (m,
H), 2.14 ~ 2.05 (m, 2H), 2.05 ~ 1.96 (m, 1H), 1.84 ~ 1.73 (m, 1H), 1.54 ~ 1.47 (m,
CDCl
3
1
2
1
2
1
2
2
2
1
3
3
H), 1.30 ~ 1.20 (m, 16H), 0.86 (t, 3H). C NMR (125 MHz, CDCl ): δ 214.7, 135.1,
1
18.8, 83.2, 64.4, 36.0, 34.3, 31.9, 30.1, 29.6, 29.5, 29.4, 29.3, 26.0, 22.6, 17.4, 14.1.
+
24.5
HRMS (EI+) m/z calculated for C18
H
32
O
2
[M] : 280.2402, found 280.2394. [α]
D
=
-
53.82 (c = 1.0, CH Cl ), Enantiomeric excess was determined to be 86% ee by chiral
2 2
o
1 2
GC (Cyclosil B column, 150 C, 1.2 mL/min, t = 104.36 min, t = 10.66 min(major)).
S１２

O
O
2
-(But-3-enyloxy)-2-vinyl-cyclopentanone (8)
Cyclopentanone 8 was prepared according to the general procedure for ring
expansion at room temperature starting from allenylcyclobutanol 7 (54mg,
0
.30mmol).Yield 42mg (78%).
R (25% ether in pet. ether): 0.60. IR (neat): 3079, 2965, 1743, 1641, 1452, 1406,
f
-1 1
1
3
382, 1272, 1165, 1118, 1072, 994, 928, 807, 714cm . H NMR (400 MHz, CDCl ):
δ 5.85 ~ 5.74 (m, 2H), 5.40 (dd, J = 11.0 Hz, J = 1.0 Hz, 1H), 5.35 (dd, J = 17.5 Hz,
1
2
1
J
2
= 1.0 Hz, 1H), 5.09 ~ 5.00 (m, 2H), 3.51 ~ 3.47 (m, 1H), 3.44 ~ 3.40 (m, 1H),
.39~ 2.23 (m, 4H), 2.14 ~ 2.08 (m, 2H), 2.07 ~ 2.00 (m, 1H), 1.84 ~ 1.78 (m, 1H).
2
1
3
C NMR (125 MHz, CDCl
4.5, 34.3, 17.4. [α]D = - 68.94 (c = 0.84, CH Cl ), Enantiomeric excess was
3
): δ 214.5, 135.0, 134.9, 119.1, 116.3, 83.3, 63.7, 36.0,
2
2.9
3
2
2
o
1
determined to be 87% ee by chiral GC (Cyclosil B column, 60 C, 1.0 flow rate, t =
6
2
6.77 min, t = 66.84 min (major)).
O
O
6
-Oxa-spiro[4.5]dec-9-en-1-one (21)
To a solution of the cyclopentanone 8 (20mg, 0.11mmol) in methylene chloride
15mL) was added Grubbs II catalyst (7.0mg, 0.011mmol). The solution was stirred at
(
room temperature overnight, and then concentrated in vacuo followed by purified
with flash chromatography (10% diethyl ether in petroleum ether, silica gel). Desired
product 21 bearing a spiro-ring was obtained as a yellowish oily liquid (20mg, 100%).
R
f
(25% ether in pet. ether): 0.65. IR (neat): 3035, 2963, 2835, 1739, 1652, 1463,
1
6
4
2
429, 1405, 1371, 1338, 1274, 1207, 1157, 1130, 1075, 1050, 954, 903, 824, 768,
-1 1
99cm . H NMR (400 MHz, CDCl
3
): δ 6.12 ~ 6.08 (m, 1H), 5.49 ~ 5.46 (m, 1H),
.03 ~ 3.98 (m, 1H), 3.80 ~ 3.76 (m, 1H), 2.49 ~ 2.42 (m, 1H), 2.33 ~ 2.17 (m, 2H),
1
3
.11 ~ 2.03 (m, 2H), 2.02 ~ 2.00 (m, 1H), 1.96 ~ 1.87 (m, 2H). C NMR (125 MHz,
CDCl
calculated for C
CH Cl
column, 60 C, 1.0 flow rate, t = 67.14 min, t = 67.21 min (major)).
3
): δ 215.4, 128.1, 125.6, 78.8, 60.7, 36.9, 35.5, 24.9, 17.9 HRMS (EI+) m/z
+
23.2
9
H
12
O
2
[M] :152.0837, found: 152.0839. [α]
D
= 186.97 (c = 0.60,
2
2
), Enantiomeric excess was determined to be 86% ee by chiral GC (Cyclosil B
o
1
1
O
O
2
-(Pent-4-enyloxy)-2-vinyl-cyclopentanone (10)
Cyclopentanone 10 was prepared according to the general procedure for ring
expansion at room temperature starting from allenylcyclobutanol 9 (78mg,
.50mmol).Yield 78mg (100%).
0
R
f
(25% ether in pet. ether): 0.50. IR (neat): 3078, 2941, 2883, 1744, 1641, 1449,
S１３

-
1 1
1
406, 1272, 1165, 1129, 1080, 994, 913, 812, 714, 672cm . H NMR (400 MHz,
CDCl ): δ 5.85 ~ 5.75 (m, 2H), 5.39, (dd, J = 11.0 Hz, J = 1.0 Hz, 1H), 5.34 (dd, J
3
1
2
1
=
2
17.5 Hz, J = 1.0 Hz, 1H), 5.03 ~ 4.93 (m, 2H), 3.45 ~ 3.35 (m, 2H), 2.39~ 2.23 (m,
1
3
2
H), 2.13 ~ 2.00 (m, 5H), 1.85 ~ 1.73 (m, 1H), 1.66 ~ 1.61 (m, 2H). C NMR (125
MHz, CDCl ): δ 214.7, 138.2, 135.0, 118.9, 114.6, 83.2, 63.6, 36.0, 34.2, 30.1, 29.2,
3
+
1
7.4. HRMS (EI+) m/z calculated for C12
= -82.08 (c = 1.0, CH Cl ), Enantiomeric excess was determined to be 86% ee
2 2
by chiral GC (Cyclosil B column, 60 C, 1.0 flow rate, t
H
18
O
2
[M] : 194.1307, found: 194.1309.
2
D
2.6
[
α]
o
1
2
= 67.72 min, t = 66.75 min
(
major)).
O
O
6
-Oxa-spiro[4.6]undec-10-en-1-one (22)
To a solution of the cyclopentanone 10 (70mg, 0.36mmol) in methylene chloride
30mL) was added Grubbs II catalyst (226mg, 0.036mmol). The solution was stirred
(
at room temperature overnight, and then concentrated in vacuo followed by purified
with flash chromatography (10% diethyl ether in petroleum ether, silica gel). Desired
product 22 bearing a spiro-ring was obtained as a yellowish oily liquid (70mg, 100%).
f
R (25% ether in pet. ether): 0.40. IR (neat): 3020, 2954, 1740, 1434, 1206, 1155,
-
1 1
1
~
2
1
3
1
125, 1093, 1054, 1003, 937, 802, 748, 697cm . H NMR (500 MHz, CDCl
5.88 (m, 1H), 5.25 (d, J = 12.0 Hz, 1H), 3.88 ~ 3.83 (m, 1H), 3.79 ~ 3.74 (m, 1H),
.45 ~ 2.38 (m, 1H), 2.35 ~ 2.26 (m, 2H), 2.22 ~ 2.14 (m, 2H), 2.08 ~ 1.99 (m, 1H),
3
): δ 5.93
1
3
.90 ~ 1.78 (m, 4H). C NMR (125 MHz, CDCl
7.3, 35.2, 29.1, 25.8, 17.9. HRMS (EI+) m/z calculated for C10
= 96.75 (c = 1.10, CH Cl ), Enantiomeric excess
was determined to be 85% ee by chiral GC (Cyclosil B column, 55 C, 1.0 flow rate, t
3
): δ 214.5, 132.7, 128.6, 84.8, 65.3,
+
H
14
O
2
[M] :
23.5
D
66.0994, found: 166.0991. [α]
2 2
o
1
=
78.11 min, t = 78.22 min (major)).
1
O
O
2
-(Pent-3-ynyloxy)-2-vinylcyclopentanone (12)
Cyclopentanone 12 was prepared according to the general procedure for ring
expansion at room temperature starting from allenylcyclobutanol 11 (96.6mg,
0
.50mmol). Yield 85mg (88%).
(25% ether in pet. ether): 0.55. IR (neat): 3067, 2964, 2921, 2885, 2361, 1744,
R
f
-1 1
1
636, 1464, 1405, 1273, 1158, 1131, 1083, 993, 935, 810, 662cm . H NMR (500
): δ 5.76 (ddd, J = 17.5 Hz, J = 11.0 Hz, J = 1.0 Hz, 1H), 5.36 (dd, J
= 1.0 Hz, 1H), 5.31 (dd, J = 17.5 Hz, J = 1.0 Hz, 1H), 3.50 ~ 3.39 (m,
H), 2.34 ~ 2.25 (m, 2H), 2.24 ~ 2.19 (m, 2H), 2.10 ~ 2.06 (m, 2H), 2.04 ~ 1.95 (m,
MHz, CDCl
11.0 Hz, J
3
1
2
3
1
=
2
1
2
2
1
3
1
3
H), 1.80 ~ 1.70 (m, 1H), 1.71 (m, 3H). C NMR (125 MHz, CDCl ): δ 214.4, 134.6,
1
30.2, 119.3, 83.5, 75.6, 63.3, 35.9, 34.2, 20.5, 17.3, 3.4. HRMS (EI+) m/z calculated
+
23.3
for C12
H
16
O
2
[M] : 192.1150, found: 192.1149. [α]
D
2 2
= -63.69 (c = 1.5, CH Cl ),
S１４

Enantiomeric excess was determined to be 84% ee by chiral GC (Cyclosil B column,
o
6
0 C, 1.2 flow rate, t = 64.86 min, t = 64.96 min (major)).
1 2
O
OBn
Ph
Ph
2
-Benzyloxy-4,4-diphenyl-2-vinyl-cyclopentanone (14)
Cyclopentanone 14 was prepared from allenylcyclobutanol 13 (110mg, 0.30
mmol) according to the general procedure for ring expansion with (R,R)-Anthracene
o
Ligand L4 at 60 C. Yield 105mg (95%).
R (25% ether in pet. ether): 0.60. IR (neat): 3093, 3062, 3022, 2910, 1738, 1494,
f
-1 1
1
448, 1412, 1377, 1065, 1025, 995, 929, 731, 697cm . H NMR (500 MHz, CDCl
3
):
δ 7.31 ~ 7.15 (m, 13H), 7.00 ~ 6.98 (m, 2H), 5.71 (dd, J = 17.5 Hz, J = 11.0 Hz, 1H),
1
2
5
.23 (d, J = 11.0 Hz, 1H), 5.20 (d, J = 17.5 Hz, 1H), 4.43 (d, J = 11.0 Hz, 1H), 4.33 (d,
J = 11.0 Hz, 1H), 3.35 (dd, J = 18.0 Hz, J = 1.3 Hz, 1H), 3.23 (dd, J = 18.0 Hz, J =
1
2
1
2
1
.3 Hz, 1H), 3.20 (dd, J
1
= 14.0 Hz, J
2
= 1.2 Hz, 1H), 3.04 (dd, J
1
= 14.0Hz, J
2
= 1.2
1
3
Hz, 1H). C NMR (125 MHz, CDCl
3
): δ 212.2, 147.2, 147.1, 138.2, 135.2, 130.3,
1
5
3
28.51, 128.46, 128.1, 127.4, 127.3, 126.7, 126.6, 126.4, 126.2, 119.2, 82.5, 66.2,
+
24 2
0.6, 48.2, 47.8. HRMS (EI+) m/z calculated for C26H O [M] : 368.1776, found:
25.0
D
68.1775. [α]
2 2
= -54.08 (c=1.40, CH Cl ). Enantiomeric excess was determined to
1
be 95% ee by chiral HPLC (Chiralpak AD, heptane:i-PrOH = 99:1, 1.0 mL/min, t =
1
2
3.85 min(major), t = 18.87 min).
O
OBn
Et
Et
2
-(benzyloxy)-4,4-diethyl-2-vinylcyclopentanone (16)
Cyclopentanone 16 was prepared from allenylcyclobutanol 15 (109mg, 0.40mmol)
according to the general procedure for ring expansion with (R,R)-Anthracene Ligand
o
L4 at 60 C. Yield 100mg (92%).
f
R (25% ether in pet. ether): 0.90. IR (neat): 3032, 2964, 2937, 2879, 1740, 1638,
-
1
1
607, 1498, 1455, 1380, 1315, 1272, 1166, 1054, 1000, 934, 867, 802, 734, 697cm .
1
H NMR (500 MHz, CDCl
Hz, 1H), 5.41 (dd, J = 11 Hz, J
.51 (d, J = 11.6 Hz, 1H), 4.46 (d, J = 11.6 Hz, 1H), 2.40 (d, J = 18.0 Hz, 1H), 2.22 ~
.14(m, 2H), 2.02 (d, J = 14.5 Hz, 1H), 1.61 ~ 1.55 (m, 2H), 1.43 ~ 1.38 (m, 2H),
3
): δ 7.35 ~ 7.25 (m, 5H), 5.96 (ddd, J
1
= 17.5 Hz, J
2
=11
1
2
= 1 Hz, 1H), 5.39 (dd, J = 17.5 Hz, J
1
2
=1 Hz, 1H),
4
2
0
1
3
3
.85 ~ 0.80 (m, 6H). C NMR (125 MHz, CDCl ): δ 214.6, 138.6, 136.5, 128.2,
1
27.4, 127.3, 118.7, 83.3, 66.2, 49.5, 44.9, 38.8, 30.7, 30.3, 8.34, 8.30. HRMS (EI+)
+
22.5
m/z calculated for C18
H
24
O
2
[M] : 272.1776, found: 272.1766. [α]
D
= -67.29 (c =
1
.40, CH Cl ). Enantiomeric excess was determined to be 94% ee by chiral HPLC
2
2
(
1 2
Chiralpak OD, heptane:i-PrOH = 99.9:0.2, 0.8 mL/min, t = 18.91 min(major), t =
2
3.29 min).
S１５

O
OBn
3
-Benzyloxy-3-vinyl-spiro[4.4]nonan-2-one (18)
Cyclopentanone 18 was prepared from allenylcyclobutanol 17 (108mg, 0.40mmol)
according to the general procedure for ring expansion with (R,R)-Anthracene Ligand
o
L4 at 60 C. Yield 100mg (93%)
f
R (25% ether in pet. ether): 0.92. IR (neat): 3031, 2953, 2870, 1740, 1498, 1454,
-1 1
1
400, 1380, 1272, 1056, 1028, 934, 801, 734, 697cm . H NMR (500 MHz, CDCl ):
3
1 2 1
δ 7.33 ~ 7.24 (m, 5H), 5.97 (dd, J = 17.5 Hz, J = 11 Hz, 1H), 5.43 (dd, J = 11 Hz,
J = 1 Hz, 1H), 5.40 (dd, J = 17.5 Hz, J = 1 Hz, 1H), 4.52 (d, J = 11.5 Hz, 1H), 4.47
2
1
2
(
2
d, J = 11.5 Hz, 1H), 2.40 (dd, J
.16 (d, J = 13.5 Hz, 1H), 1.72 ~ 1.55 (m, 8H).. C NMR (125 MHz, CDCl ): δ
1
2
= 18.5 Hz, J = 1.5 Hz, 1H), 2.29 ~ 2.12 (m, 2H),
1
3
3
2
2
14.4, 138.5, 135.9, 128.2, 127.5, 127.3, 119.2, 83.9, 66.3, 50.7, 47.0, 43.4, 40.2, 23.9,
+
3.8. LRMS (ESI+) m/z calculated for C H O [M+H] : 271.2, found: 271.2.
1
8
22
+
2
22 2
HRMS (EI+) m/z calculated for C18H O [M] : 270.1620, found: 270.1620. EA
calculated for C18
2
D
2.5
H
22
O
2
: C: 79.96, H: 8.20, found: C: 79.70, H: 8.34 [α]
= -67.29
(
c = 1.40, CH Cl ). Enantiomeric excess was determined to be 92% ee by chiral
2
2
HPLC (Chiralpak OD, heptane:i-PrOH = 99.9:0.1, 0.8 mL/min, t
1
= 30.39
2
min(major), t = 33.37 min).
O
OBn
EtO C
2
EtO C
2
Diethyl-3,3'-(3-(benzyloxy)-4-oxo-3-vinylcyclopentane-1,1-diyl)dipropanoate (20)
Cyclopentanone 20 was prepared from allenylcyclobutanol 19 (125mg, 0.30mmol)
according to the general procedure for ring expansion with (R,R)-Anthracene Ligand
o
L4 at 60 C. Yield 100mg (80%)
f
R (50% ether in pet. ether): 0.60. IR (neat): 2981, 2933, 2873, 1734, 1498, 1455,
-1 1
1
379, 1305, 1245, 1182, 1098, 1027, 937, 856, 736, 698cm . H NMR (500 MHz,
CDCl ): δ 7.36 ~ 7.23 (m, 5H), 5.95 (dd, J = 17.5 Hz, J = 11.0 Hz, 1H), 5.43 (dd, J
11 Hz, J = 1 Hz, 1H), 5.39 (dd, J = 17.5 Hz, J = 1 Hz, 1H), 4.50 (d, J = 11.5 Hz,
3
1
2
1
=
2
1
2
1H), 4.46 (d, J = 11.5 Hz, 1H), 4.14 ~ 4.07 (m, 4H), 2.43 (dd, J
1 2
= 18.0 Hz, J = 1.5
Hz, 1H), 2.33 ~ 2.19 (m, 6H), 1.99 (d, J = 14.6 Hz, 1H), 1.93 ~ 1.89 (m, 2H), 1.76 ~
1
3
1
1
4
.71 (m, 2H), 1.27 ~ 1.21 (m, 6H).. C NMR (125 MHz, CDCl
73.0, 138.2, 135.7, 128.4, 128.2, 127.5, 126.9, 119.2, 82.9, 66.4, 60.6, 60.5, 49.6,
5.7, 37.8, 33.6, 32.6, 29.4, 29.3, 14.1. HRMS (ES+) m/z calculated for C24
3
): δ 212.9, 173.1,
32 6
H O
+
24.5
[
M] : 416.2199, found: 416.2194. [α]
excess was determined to be 94% ee by chiral HPLC (Chiralpak AD, heptane:i-PrOH
98:2, 0.8 mL/min, t = 25.55 min(major), t = 30.97 min).
D
2 2
= -59.82 (c = 1.65, CH Cl ). Enantiomeric
=
1
2
S１６

O
OBn
BnO
2
-Benzyloxy-4-benzyloxymethyl-2-vinyl-cyclopentanone (25)
Cyclopentanone 25 was prepared from allenylcyclobutanol 24a (168mg,
0
.50mmol) according to the general procedure for ring expansion with (R,R)-
o
Anthracene Ligand L4 at 60 C.Total yield 154mg (92%). d.r. ~ 10:1 (NMR)
Major diastereomer 25a
R (25% ether in pet. ether): 0.45. IR (neat): 3088, 3064, 3031, 2929, 2858, 1740,
f
-1
1
654, 1622, 1496, 1454, 1366, 1346, 1211, 1187, 1104, 1027, 992, 936, 736, 697cm .
1
H NMR (500 MHz, CDCl
0.8 Hz, 1H), 5.46 ~ 5.41 (m, 2H), 4.52 (s, 2H), 4.50 (d, J = 11.0 Hz, 1H), 4.36 (d, J =
1.0 Hz, 1H), 3.52 ~ 3.43 (m, 2H), 2.84 ~ 2.74 (m, 1H), 2.64 ~ 2.57 (m, 1H), 2.40 ~
.34 (m, 1H), 2.13 (dd, J = 19.1 Hz, J = 10.8 Hz, 1H), 1.80 (dd, J = 14.0 Hz, J =
3 1 2
): δ 7.40 ~ 7.23 (m, 10H), 6.01 (dd, J = 18.0 Hz, J =
1
1
2
1
1
3
1
2
1
2
1
3
0.8 Hz, 1H). C NMR (125 MHz, CDCl
3
): δ 212.4, 138.3, 138.2, 134.5, 129.0,
28.40, 128.38, 128.32, 127.7, 127.6, 127.5, 119.4, 83.2, 73.1, 72.7, 66.4, 40.4, 39.3,
+
2.4. HRMS (ES+) m/z calculated for C22
H O
24 3
[M] : 336.1725, found: 336.1726.
). Enantiomeric excess was determined to be 88%
ee by chiral HPLC (Chiralpak AD, heptane:i-PrOH = 99:1, 0.8 mL/min, t = 12.13
2
6.3
[
α]
D
2 2
= -43.97 (c = 1.60, CH Cl
1
2
min(major), t = 13.84 min).
O
OH
1
2
(
R)-2-Hydroxy-2-vinyl-cyclopentanone (26)
To a solution of the cyclopentanone 4 (500mg, 2.0mmol) in methylene chloride
(10mL) was added DDQ (550mg, 2.4mmol). The solution was stirred at room
temperature for 4h, then concentrated followed by purified with flash chromatography
50% diethyl ether in petroleum ether, silica gel). Cyclopentanone 26 was obtained as
a yellowish oily liquid (200mg, 80%).
(50% ether in pet. ether): 0.30 IR (neat): 3447, 2964, 1749, 1457, 1404, 1314,
(
R
f
-
1 1
1
260, 1160, 1089, 996, 931, 804cm . H NMR (500 MHz, CDCl
3
): δ5.88 (dd, J
1
=
1
7.5 Hz, J =10.6 Hz, 1H), 5.31 (dd, J = 17.5 Hz, J = 0.6 Hz 1H), 5.27 (dd, J
2
1
2
1
= 10.6
Hz, J = 0.6 Hz, 1H), 2.81 (s, 1H), 2.44~ 2.30 (m, 2H), 2.24 ~ 2.19 (m, 1H), 2.06 ~
2
1
3
1
1
.97 (m, 2H), 1.91 ~ 1.84 (m, 1H). C NMR (125 MHz, CDCl
16.3, 80.1, 35.6, 34.6, 16.8. [α]
3
): δ 217.9, 136.6,
2
D
5.2
= - 50.52 (c = 1.4, CHCl ) (89%ee for 4)
3
OH
OH
1
2
(
1R,2S)-1-Vinylcyclopentane-1,2-diol (27)
To a solution of the tetramethylammonium triacetoxyborohydride (660mg,
.50mmol) in acetic acid and acetonitrile (6mL, 1:1) was added dropwise the solution
2
S１７

of (R)-2-hydroxy-2-vinylcyclopentanone 26 (63mg, 0.50mmol) in acetonitrile (3ml)
o
o
at -20 C. The solution was stirred at -20 C for 24 hours and warmed up to room
temperature. Then it was quenched by saturated NaHCO and extracted with EtOAc 3
times. The combined extractions are washed with brine and dried over Na
3
2
SO4. Then
it was filtered and concentrated followed by purified with flash chromatography (50%
ethyl acetate in petroleum ether, silica gel) afforded desired product 27 as a oily liquid
(
44.mg, 71%, d.r.>10:1 from NMR. Single diastereoisomers was isolated).
R (50% EtOAc / ether): 0.44. IR (neat): 3377, 3088, 2960, 1710, 1641, 1416,
f
-1 1
1
3
292, 1198, 1130, 1069, 998, 970, 922, 886cm . H NMR (500 MHz, CDCl ): δ6.15
(
dd, J = 17.5 Hz, J =10.9 Hz, 1H), 5.40 (dd, J = 17.5 Hz, J = 1.3 Hz 1H), 5.29 (dd,
1
2
1
2
J
1
2
= 10.9 Hz, J = 1.3 Hz, 1H), 3.86 ~ 3.84 (m, 1H), 2.24 ~ 2.17 (m, 1H), 2.06 ~ 2.00
1
3
(m, 1H), 1.86 ~ 1.80 (m, 2H), 1.73 ~ 1.60 (m + broad, 4H). C NMR (125 MHz,
2
D
3.2
CDCl
3
): δ 139.9, 115.3, 83.8, 80.4, 35.7, 32.1, 20.2. [α]
3
= - 70.19 (c = 1.1, CHCl )
3
2.5, 30.9, 14.1
Reference
1
) Perrin, D. D. Armarego, W. L. F. Purification of Laboratory Chemicals;
Pergamon Press: New York, 1988.
2
) Ukai, T.; Kawazura, H.; Ishii, Y.; Bonnet, J. J.; Ibers, J. A. J. Organometallic
Chem. 1974, 65, 253.
3
4
) Trost, B. M.; Van Vranken, D. L.; Bingel, C. J. Am. Chem. Soc. 1992, 114, 9327.
) Trost, B. M.; Bunt, R. C.; Lemoine, R. C.; Calkins, T. L. J. Am. Chem. Soc. 2000,
1
22, 5968.
5
) a) Trost, B.M.; Jäkel, C; Plietker, B; J. Am. Chem. Soc. 2003, 125, 4438. b) Trost,
B.M.; Simas, A.B.C.; Plietker, B; Jäkel, C; Xie, J.; Chem. Eur. J. 2005, 125, 4438
) Harvey, D. F.; Lund, K. P.; Neil, D. A.; J. Am. Chem. Soc. 1992, 114, 22,
) Neeson, S. J.; Stevenson, P. J. Tetrahedron 1989, 45(19), 6239.
) Floegel, Oliver; Reissig, Hans-Ulrich. Eur. J. Org. Chem. 2004, 13, 2797.
) Krepski, L.R.; Hassner, A.; J. Org. Chem. 1978, 43(14), 2879.
6
7
8
9
1
0) Cao, W.; Erden, I.; Grow, R.H.; Keeffe, J.R.; Song, J.; Trudell, M.B.; Wadsworth,
T.L.; Xu, F.; Zheng, J. Can. J. of Chem. 1999, 77(5/6), 1009.
11) Johnston, B.D.; Czyzewska, E.; Oehlschlager, A.C. J. Org.Chem. 1987, 52, 3693.
1
2) a) Brown, M.J.; Harrison, T.; Overman, L.E.; J. Am. Chem. Soc. 1991, 125, 5365.;
b) Brown, M.J.; Harrison, T.; Overman, L.E.; J. Am. Chem. Soc. 1991, 125, 5378.
S１８

Part B: Spectrum Section
S１９

S２０

S２１

2
.00
.03
2
0
.80
.02
2
2.96
S２２

S２３

2.00
2
.03
.86
0
1.95
2
.14
.32
3
S２４

0
.59
.51
1
1.74
2.00
16.57
3.40
S２５

0.81
0.95
2.00
1.96
2
.16
.19
2
S２６

0.85
0
.91
.00
2
1.90
2.11
2
.13
.17
2
S２７

0
.66
.00
2
2.24
2
.36
.34
3
S２８

6
.12
.93
3
2.00
S２９

8
.07
.85
1
4.57
S３０