Enantiomerically pure allylboronic esters as versatile reagents in the enantioselective synthesis of dihydro-α-pyrone-containing natural products

Article abstract of DOI:10.1055/s-0032-1318440

A short and efficient enantio- and diastereoselective synthesis of different representatives from the class of dihydro-α-pyrone natural products, including both enantiomers of goniothalamin, massoia lactone, parasorbic acid, and some derivatives is presented. It is based on the application of enantiopure α-chiral allylboronic esters in allyl additions. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0032-1318440

1106▌
PAPER
paper
Enantiomerically Pure Allylboronic Esters as Versatile Reagents in the
Enantioselective Synthesis of Dihydro-α-pyrone-Containing Natural Products
Allylboronic Esters in Total Synthesis
Sean Bartlett,a Dietrich Böse,b Daniel Ghori,b Bastian Mechsner,b Jörg Pietruszka*b
a
School of Chemistry, University of Bristol, Cantock’s Close, Bristol BS8 1TS, UK
b
Institut für Bioorganische Chemie der Heinrich-Heine-Universität Düsseldorf im Forschungszentrum Jülich, Stetternicher Forst, Geb. 15.8,
52426 Jülich, Germany
Fax +49(2461)611669; E-mail: j.pietruszka@fz-juelich.de
Received: 29.01.2013; Accepted after revision: 19.02.2013
kinetic resolution of racemic allylic alcohols.6 Other total
Abstract: A short and efficient enantio- and diastereoselective
syntheses have been developed in similar ways, adding
synthesis of different representatives from the class of dihydro-
some steps for the insertion of the styryl substituent via
α-pyrone natural products, including both enantiomers of goniothal-
amin, massoia lactone, parasorbic acid, and some derivatives is pre-
olefination.3,7 Another attempt is based on Jacobsen’s hy-
sented. It is based on the application of enantiopure α-chiral drolytic kinetic resolution of epoxides.8
allylboronic esters in allyl additions.
Some naturally occurring alkylpyrones such as parasorbic
acid (2), isolated from mountain ash berries (Sorbus aucu-
paria), or massoia lactone (3) (Figure 1), isolated from the
Key words: natural products, goniothalamin, allyl addition, boron-
ic ester, dihydro-α-pyrones
bark oil of Cryptocarya massoia and jasmine flowers, ei-
ther feature bioactivity as well or are used as intermedi-
ates in the synthesis of other natural products.4a One
approach towards the total synthesis of these compounds
is identical to the three-step synthesis of goniothalamin
(1) as described previously by Brown.4a
Dihydro-α-pyrones, or more precisely 6-substituted 5,6-
dihydro-2H-pyran-2-ones, represent an interesting group
of bioactive natural products that have been isolated from
many different plants, in particular from the Lauraceae,
Annonaceae, Piperaceae, and Psilotaceae families.1
Some of these have been proven to show cytotoxicity as
well as antibacterial, antiviral, or antifungal properties.2
Dihydro-α-pyrones can be divided into alkyl-, aryl-, and
alkenyl-substituted pyrones as three main subcategories.
O
O
O
O
O
O
Ph
1
2
3
The naturally occurring styrylpyrone goniothalamin (1)
was isolated first in 1967 by Hlubucek and Robertson
from the bark of Cryptocarya caloneura.1b Later it was
also observed in various other species of the genera Cryp-
tocarya (Lauraceae) and Goniothalamus (Annonace-
ae).1a,c The cytotoxic and antiproliferative activity of
goniothalamin (1) and its derivatives against specific
cancer cell lines has been verified in several studies, in-
cluding the development of a structure–activity relation-
ship.2b,f,g,3 It was concluded that the mechanism of action
in human breast cancer involved cell death due to apopto-
sis.2d Moreover some studies have revealed a trypanocidal
activity against Trypanosoma cruzi, which is known as
the cause of South American Chagas disease.2c Due to the
biological activity of goniothalamin (1) and its deriva-
tives, a number of total syntheses (3–12 steps) have been
reported in the literature. Most of these are based on a se-
quence consisting of allylation, esterification, and ring-
closing metathesis (RCM), starting from trans-cinnamal-
dehyde or cinnamyl alcohol. The chirality was induced by
using chiral allylmetal reagents (Brown, Leighton),4
asymmetric catalysis (Krische, Maruoka),3,5 or enzymatic
Figure 1 Structures of goniothalamin (1), parasorbic acid (2), and
massoia lactone (3)
OH
OH
OH
OH
B*
5 B*
4
Bent
*
Bent
*
ent-4
ent-5
Ph
Ph
Ph
Ph
MeO
MeO
MeO
Bent* =
O
B* =
O
MeO
B
B
O
O
Ph
Ph
Ph
Ph
Figure 2 Allylboronic esters 4 and 5
As a part of our ongoing project focused on the develop-
ment of efficient allylboron reagents 4 and 5 for allyl ad-
ditions to obtain enantioenriched homoallylic alcohols,
we have developed a family of new reagents for the ste-
reocontrolled synthesis of ene-1,5-diols 6–13 (Figure 2).9
The ease of access to these reagents, their stability, high
stereoselectivity, and the mild conditions of the allyl addi-
tions make the use of this method appropriate for multi-
SYNTHESIS 2013, 45, 1106–1114
Advanced online publication: 07.03.2013
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0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0032-1318440; Art ID: SS-2013-T0089-OP
© Georg Thieme Verlag Stuttgart · New York

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Allylboronic Esters in Total Synthesis
1107
step synthesis. The allylboronic esters have previously The results of allyl addition of reagents 4, 5 to various al-
been used successfully in the stereoselective total synthe- dehydes 19–26 are summarized in Table 1. In all cases the
sis of rugulactone.9c
reaction proceeded with excellent diastereoselectivity
with respect to the double bond configuration. The diaste-
reomeric ratio was determined by 1H NMR analysis of the
crude product, and in all cases no E-configured byproduct
could be detected (dr > 20:1). To ensure full conversion,
the reactions were conducted for three days at room tem-
perature. All products were isolated after column chroma-
tography in good (72%, 6) to excellent (99%, ent-12)
yields. The enantiomeric purities, which were determined
by chiral HPLC, were also found to vary from good (91%,
11) to excellent (99%, 6) values. In earlier studies it could
be shown that the product enantiomeric excess is highly
related to the diastereomeric purity of the allylboron re-
agents 4 and 5.9c
Herein we wish to demonstrate the scope of the method
towards the synthesis of 5,6-dihydro-2H-pyran-2-one
containing natural products such as goniothalamin (1),
parasorbic acid (2), massoia lactone (3), and their deriva-
tives and analogues 14–18. The retrosynthetic approach
towards these compounds is highlighted in Scheme 1. Ac-
cordingly the major part of the lactone can be installed by
a selective oxidation of 2-ene-1,5-diols 6–13. These enan-
tioenriched Z-configured diols can be selectively synthe-
sized via the addition of allylboronic esters 4 or 5 to
different aldehydes 19–26.
oxidation
The stereochemical outcome of the allyl addition can be
explained by the transition states shown in Scheme 2. It is
noteworthy that the allyl addition using allylboronic ester
4 and its diastereomer ent-5 (containing the enantiomeric
auxiliary Bent*) both lead to the same enantiomer of the
product 6–13.
O
OH
OH
OH
+
(Bent*)
*B
O
O
R
R
R
allyl addition
1, 2, 3 and
14–18
6–13
4–5
Scheme 1 Retrosynthetic analysis of 5,6-dihydro-2H-pyran-2-ones
1–3 and 14–18
Table 1 Allyl Additions of Allylboron Reagents 4 and 5 to Different Aldehydes 19–26
Entry RCHO
Aldehyde Allylboronate (R)-Product
Yielda (%) ee (%)
Allylboronate (S)-Product
Yielda (%) ee (%)
1
2
3
Me
19
20
21
5
5
5
6
7
8
72
91
91
99
99
95
4
4
4
ent-6
ent-7
ent-8
85
85
85
98
93
94
PrCHO
Me(CH2)4CHO
4
5
22
23
ent-5
ent-5
9
70
78
94
95
ent-4
ent-4
ent-9
88
92
94
93
O
O
O
OMe
F
10
ent-10
6
7
8
24
25
26
ent-5
11
12
13
85
93
90
91
97
97
ent-4
ent-11
ent-12
ent-13
95
99
91
97
95
95
O2N
4
4
5
5
O
NO2
O
a Isolated yield after flash column chromatography.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 1106–1114

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S. Bartlett et al.
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× 4.6 mm, Daicel column. Optical rotations were measured using a
quartz cell with 1-mL capacity and a 10-cm path length. Melting
points are uncorrected. Synthesis of allylboronic esters 4, 5, ent-4,
and ent-5 was accomplished according to literature procedures.9b
(Bent*)
B*
OH
OH
H
OH
R
O
R
O
CH2Cl2, r.t.
H
R
4
B*
Addition of Allylboronic Esters 4 and 5 to Aldehydes 19–26;
General Procedure A
OH
(Bent*)
ent-5
ent-6 to ent-8
and 9–13
(S)-allylboronic ester
Aldehyde 19–26 (5.00 equiv) was added to a precooled soln (0 °C)
of the allylboronic ester 4, 5, ent-4, or ent-5 (1.00 equiv) in anhyd
CH2Cl2 (0.5 mL/mmol allylboronic ester) before warming to r.t..
The mixture was stirred until full conversion as determined by TLC.
The solvent was removed under reduced pressure and the products
were purified by column chromatography to afford the allylic alco-
hols 6–13.
OH
(Bent*)
*B
H
OH
OH
R
R
O
O
R
CH2Cl2, r.t.
5
B*
6–8 and
HO
(Bent*)
ent-4
ent-9 to ent-13
(R)-allylboronic ester
Oxidation of Allylic Alcohols 6–13 to Lactones 1–3 and 14–18;
General Procedure B
Scheme 2 Proposed transition states for the allyl addition
To a soln of alcohols 6–13 in CH2Cl2 were added PhI(OAc)2 (4–
6 equiv) and TEMPO (0.2 equiv). The soln was stirred at r.t. until
full conversion was determined, and the reaction was quenched
with a mixture of sat. aq NaHCO3 (5 mL) and aq 10% Na2S2O3
(5 mL). The layers were separated and the aqueous layer was ex-
tracted with Et2O (3 × 5 mL). The combined organic layers were
dried (MgSO4), filtered, concentrated in vacuo, and purified by col-
umn chromatography to afford the lactones 1–3 and 14–18.
With the 2-ene-1,5-diols 6–13 in hand we turned our at-
tention towards the synthesis of the 5,6-dihydro-2H-py-
ran-2-one containing natural products 1–3 and their
derivatives 14–18 by means of oxidative ring closure.
Therefore 2-ene-1,5-diols 6–13 were directly oxidized to
the corresponding lactones 1–3 and 14–21 using an excess
of (diacetoxyiodo)benzene and catalytic amounts of
2,2,6,6-tetramethylpyrrolidin-1-oxyl (TEMPO). The re-
sults of this reaction, which are summarized in Table 2,
vary from moderate (30%, ent-2) to excellent (98%, ent-
3) yields.
(2Z,5R,6E)-7-Phenylhepta-2,6-diene-1,5-diol (9)
According to general procedure A using allylboronic ester ent-5
(350 mg, 0.65 mmol) and cinnamaldehyde (21, 0.25 mL,
1.97 mmol); after 3 d, workup of the reaction followed by column
chromatography (CH2Cl2–MeOH, 99:1) gave 9 (94 mg, 70%) as a
colorless oil; 94% ee [HPLC (flow rate 0.5 mL/min, 20% i-PrOH–
heptane): tR = 14.7 (9), 17.9 min (ent-9)]; Rf = 0.2 (PE–EtOAc,
60:40); [α]D20 +83.4 (c 0.21, CHCl3).
In conclusion we have reported the enantioselective syn-
thesis of both enantiomers of goniothalamin (1 and ent-1)
and a number of derivatives employing highly stereose-
lective allyl additions of allylboronic esters 4 and 5 as the
source of chirality. The synthesis was short (two steps
starting from cinnamaldehyde), efficient [51% for (R)-go-
niothalamin (1) and 64% for (S)-goniothalamin (ent-1)
overall yield], and highly selective (94% ee for both enan-
tiomers 1 and ent-1). The success of this total synthesis
shows the versatility and viability of the family of α-sub-
stituted allylboronic esters. Further applications of these
reagents in natural product synthesis are currently under
investigation in our laboratories.
FT-IR (film): 3332, 3023, 2871, 1494, 1029, 966, 749, 697 cm–1.
1H NMR (600 MHz, CDCl3): δ = 1.96 (br, 1 H, OH), 2.05 (br, 1 H,
OH), 2.45 (dddd, 2J = 14.2 Hz, 3J = 7.4 Hz, 3J = 4.7 Hz,
4J = 1.3 Hz, 1 H, H4b), 2.50 (dddd, 2J = 14.2 Hz, 3J = 8.7 Hz,
3J = 7.4 Hz, 4J = 1.3 Hz, 1 H, H4a), 4.15 (ddd, 2J = 12.3 Hz,
3J = 7.0 Hz, 4J = 1.1 Hz, 1 H, H1b), 4.22 (ddd, 2J = 12.3 Hz,
3J = 7.0 Hz, 4J = 1.1 Hz, 1 H, H1a), 4.37 (mc, 1 H, H5), 5.69
(ddddd, 3J = 11.0 Hz, 3J = 7.4 Hz, 3J = 7.4 Hz, 4J = 1.1 Hz,
4J = 1.1 Hz, 1 H, H3), 5.91 (ddddd, 3J = 11.0 Hz, 3J = 7.0 Hz,
3J = 7.0 Hz, 4J = 1.3 Hz, 4J = 1.3 Hz, 1 H, H2), 6.26 (dd,
3J = 15.9 Hz, 3J = 6.4 Hz, 1 H, H6), 6.62 (dd, 3J = 15.9 Hz,
3
4J = 1.3 Hz, 1 H, H7), 7.25 (t, J = 7.4 Hz, 1 H, H11), 7.32 (dd,
3J = 7.4 Hz, 3J = 7.4 Hz, 2 H, H10), 7.38 (d, 3J = 7.4 Hz, 2 H, H9).
13C NMR (151 MHz, CDCl3): δ = 35.3 (C4), 57.9 (C1), 71.6 (C5),
126.5 (C9), 127.8 (C11), 128.6 (C3), 128.6 (C10), 130.7 (C7), 131.4
(C6), 131.8 (C2), 136.4 (C8).
Unless otherwise specified the reactions were carried out using
standard Schlenk techniques under dry N2 with magnetic stirring.
Glassware was oven dried at 120 °C overnight. Solvents were dried
and purified by conventional methods prior to use. All reagents
were used as purchased from commercial suppliers without further
purification. Common solvents for chromatography [petroleum
ether (PE) bp 40–60 °C, EtOAc] were distilled prior to use. Flash
column chromatography was performed on silica gel 60, 0.040–
0.063 mm (230–400 mesh). TLC (monitoring the course of the re-
action) was performed on pre-coated plastic sheets with detection
by UV (254 nm) and/or by coloration with cerium molybdenum
soln [phosphomolybdic acid (25 g), Ce(SO4)2·H2O (10 g), concd
H2SO4 (60 mL), H2O (940 mL)]. 1H and 13C NMR spectra were re-
corded at r.t. in CDCl3 on a spectrometer at 600 and 151 MHz re-
spectively, relative to internal standard TMS (1H: δTMS = 0.00) or
relative to the resonance of the solvent [13C: δ(CDCl3) = 77.0].
Higher order δ and J values are not corrected. 13C signals were as-
signed by means of C, H, COSY and HSQC, or HMBC spectrosco-
py. Enantiomeric excesses were determined by HPLC analysis
using Dionex (UltiMate® 3000) equipped with a Chiralpak IC, 250
MS (EI, 70 eV): m/z (%) = 186 (9, [(M – H2O)+]), 131 (100,
+
+
+
[C9H7O+]), 104 (77, [C8H8 ]), 91 (10, [C7H7 ]), 77 (13, [C6H5 ]).
FT-ICR-MS: m/z [M + Na]+ calcd for C13H16O2Na: 227.1048;
found: 227.1043.
(2Z,5S,6E)-7-Phenylhepta-2,6-diene-1,5-diol (ent-9)
According to general procedure A using allylboronic ester ent-4
(350 mg, 0.65 mmol) and cinnamaldehyde (21, 0.25 mL,
1.97 mmol); after 3 d, workup of the reaction followed by column
chromatography (CH2Cl2–MeOH, 99:1) gave ent-9 (118 mg, 88%)
as a colorless oil; [α]D20 –85.9 (c 0.20, CHCl3), 94% ee. The spec-
troscopic data are identical with those of diol 9.
(2Z,5R,6E)-7-(4-Methoxyphenyl)hepta-2,6-diene-1,5-diol (10)
According to general procedure A using allylboronic ester ent-5
(350 mg, 0.65 mmol) and 4-methoxycinnamaldehyde (22, 327 mg,
1.97 mmol); after 8 d, workup of the reaction followed by column
chromatography (CH2Cl2–MeOH, 98:2) gave 10 (120 mg, 78%) as
Synthesis 2013, 45, 1106–1114
© Georg Thieme Verlag Stuttgart · New York

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Allylboronic Esters in Total Synthesis
1109
Table 2 Oxidation towards 5,6-Dihydro-2H-pyran-2-one Containing Natural Products [(S)-Products from Diols ent-6 through ent-13]
AcO
OAc
OH
O
I
CH2Cl2, r.t.
OH
*
O
*
+
TEMPO (20 mol%)
R
R
6–13
(4–6 equiv)
1–3 and 14–18
Entry
1,5-Diol
Product
(R)-Product
ent-2
Yielda (%)
30
(S)-Product
Yielda (%)
39
O
O
1
2
6
7
2
O
O
14
50
ent-14
50
2
O
O
3
4
8
9
3
1
82
73
ent-3
ent-1
98
73
4
O
O
Ph
O
O
5
6
7
8
10
11
12
13
15
16
17
18
52
77
78
80
ent-15
ent-16
ent-17
ent-18
52
77
59
77
OMe
O
O
F
O
O
NO2
O
O
NO2
a Isolated yield after column chromatography.
a colorless solid; mp 58 °C; 95% ee [HPLC (flow rate 0.5 mL/min,
20% i-PrOH–heptane): tR = 22.6 (10), 27.6 min (ent-10)]; Rf = 0.1
(PE–EtOAc, 60:40); [α]D20 +77.6 (c 0.48, CHCl3).
1H NMR (600 MHz, CDCl3): δ = 1.99 (br, 2 H, OH), 2.43 (dddd,
2J = 14.2 Hz, 3J = 7.4 Hz, 3J = 4.7 Hz, 4J = 1.3 Hz, 1 H, H4b), 2.50
(dddd, 2J = 14.2 Hz, 3J = 8.7 Hz, 3J = 7.4 Hz, 4J = 1.3 Hz, 1 H,
H4a), 3.81 (s, 3 H, OCH3), 4.14 (ddd, J = 12.3 Hz, J = 7.0 Hz,
4J = 1.1 Hz, 1 H, H1b), 4.22 (ddd, 2J = 12.3 Hz, 3J = 7.0 Hz,
4J = 1.1 Hz, 1 H, H1a), 4.34 (mc, 1 H, H5), 5.69 (ddddd,
3J = 11.0 Hz, 3J = 7.4 Hz, 3J = 7.4 Hz, 4J = 1.1 Hz, 4J = 1.1 Hz,
2
3
FT-IR (film): 3334, 3013, 2935, 2835, 1607, 1512, 1250, 1175,
1032, 969, 816 cm–1.
© Georg Thieme Verlag Stuttgart · New York
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S. Bartlett et al.
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1 H, H3), 5.91 (ddddd, 3J = 11.0 Hz, 3J = 7.0 Hz, 3J = 7.0 Hz,
4J = 1.3 Hz, 4J = 1.3 Hz, 1 H, H2), 6.12 (dd, 3J = 15.9 Hz,
3J = 6.8 Hz, 1 H, H6), 6.55 (dd, 3J = 15.9 Hz, 4J = 1.3 Hz, 1 H, H7),
6.86 (d, 3J = 6.6 Hz, 2 H, H10), 7.32 (d, 3J = 6.6 Hz, 2 H, H9).
13C NMR (151 MHz, CDCl3): δ = 35.3 (C4), 55.3 (OCH3), 57.9
(C1), 71.8 (C5), 114.1 (C10), 127.7 (C9), 128.7 (C3), 129.2 (C6),
129.2 (C8), 130.3 (C7), 131.7 (C2), 159.4 (C11).
heptane): tR = 44.4 (12), 47.7 min (ent-12)]; Rf = 0.3 (CH2Cl2–
MeOH, 97:3); [α]D20 +56.7 (c 0.93, CHCl3).
FT-IR (film): 3342, 1521, 1345, 967, 742 cm–1.
1H NMR (600 MHz, CDCl3): δ = 2.21 (br, 1 H, OH), 2.60 (br, 1 H,
OH), 2.45–2.55 (m, 2 H, H4a, H4b), 4.16 (ddd, 2J = 12.4 Hz,
3J = 6.9 Hz, 4J = 0.9 Hz, 1 H, H1a), 4.22 (ddd, 2J = 12.4 Hz,
3J = 7.0 Hz, 4J = 1.0 Hz, 1 H, H1b), 4.42 (dddd, 3J = 7.0 Hz,
3J = 6.2 Hz, 3J = 4.6 Hz, 4J = 1.5 Hz, 1 H, H5), 5.69 (ddd,
3J = 11.0 Hz, 3J = 8.0 Hz, 3J = 7.6 Hz, 4J = 1.0 Hz, 4J = 0.9 Hz,
1 H, H3), 5.89–5.95 (m, 1 H, H2), 6.23 (dd, 3J = 15.8 Hz,
3J = 6.2 Hz, 1 H, H6), 7.08 (dd, 3J = 15.8 Hz, 4J = 1.5 Hz, 1 H, H7),
MS (EI, 70 eV): m/z (%) = 216 (10, [(M – H2O)+]), 163 (100,
+
+
+
[C10H11O2 ]), 145 (16, [C10H9O+]), 91 (12, [C7H7 ]), 77 (8, [C6H5 ]).
Anal. Calcd for C14H18O3: C, 71.77; H, 7.74. Found: C, 71.60; H,
7.66.
3
3
4
7.40 (ddd, J = 8.3 Hz, J = 7.0 Hz, J = 1.8 Hz, 1 H, H11), 7.55–
3
4
7.60 (m, 2 H, H12, H13), 7.92 (dd, J = 8.3 Hz, J = 0.9 Hz, 1 H,
(2Z,5S,6E)-7-(4-Methoxyphenyl)hepta-2,6-diene-1,5-diol (ent-
10)
H10).
According to general procedure A, allylboronic ester ent-4 (350 mg,
0.65 mmol) and 4-methoxycinnamaldehyde (22, 327 mg,
1.97 mmol); after 8 d, workup of the reaction followed by column
chromatography (CH2Cl2–MeOH, 98:2) gave ent-10 (142 mg,
92%) as a colorless oil; [α]D20 –84.5 (c 0.49, CHCl3); 93% ee. The
spectroscopic data are identical with those of diol 10.
13C NMR (151 MHz, CDCl3): δ = 35.0 (C4), 57.8 (C1), 71.1 (C5),
124.6 (C10), 125.8 (C7), 128.2 (C3), 128.2 (C11), 128.8 and 133.1
(C12, C13), 131.9 (C2), 137.0 (C8), 147.9 (C9).
MS (EI, 70 eV): m/z (%) = 178 (55, [(M – C4H7O)+]), 176 (57,
+
+
[C9H10NO3 ]), 132 (74, [C9H8O+]), 77 (70, [C6H5 ]).
Anal. Calcd for C13H15NO4: C, 62.64; H, 6.07. Found: C, 62.36; H,
6.07.
(2Z,5R,6E)-7-(4-Fluorophenyl)hepta-2,6-diene-1,5-diol (11)
According to general procedure A using allylboronic ester ent-5
(497 mg, 0.93 mmol) and 4-fluorocinnamaldehyde (23, 0.37 mL,
2.80 mmol); after 3 d, workup of the reaction followed by column
chromatography (CH2Cl2–MeOH, 95:5) gave 11 (176 mg, 85%) as
a colorless oil; 91% ee [HPLC (flow rate 0.5 mL/min, 10% i-PrOH–
heptane): tR = 26.6 (11), 29.0 min (ent-11)]; Rf = 0.1 (PE–EtOAc,
60:40); [α]D20 +75.0 (c 0.52, CHCl3).
(2Z,5S,6E)-7-(2-Nitrophenyl)hepta-2,6-diene-1,5-diol (ent-12)
According to general procedure A using allylboronic ester 5
(320 mg, 0.60 mmol) and 2-nitrocinnamaldehyde (24, 318 mg,
1.80 mmol); after 3 d, workup of the reaction followed by column
chromatography (CH2Cl2–MeOH, 98:2) gave ent-12 (148 mg,
99%) as a colorless oil; [α]D20 –56.3 (c 0.94, CHCl3); 95% ee. The
spectroscopic data are identical with those of diol 12.
FT-IR (film): 3338, 3018, 2932, 2876, 1602, 1509, 1228, 968, 816
cm–1.
(2Z,5R,6E)-7-(4-Nitrophenyl)hepta-2,6-diene-1,5-diol (13)
According to general procedure A using allylboronic ester 4
(377 mg, 0.71 mmol) and 4-nitrocinnamaldehyde (25, 375 mg,
2.12 mmol); after 3 d, workup of the reaction followed by column
chromatography (CH2Cl2–MeOH, 98:2) gave 13 (159 mg, 90%) as
a yellow solid; mp 85 °C; 97% ee [HPLC (flow rate 0.5 mL/min,
20% i-PrOH–heptane): tR = 34.9 (13), 30.8 min (ent-13)]; Rf = 0.3
(CH2Cl2–MeOH, 97:3); [α]D20 +129.3 (c 0.99, CHCl3).
1H NMR (600 MHz, CDCl3): δ = 1.92 (br, 1 H, OH), 2.08 (br, 1 H,
OH), 2.44 (dddd, 2J = 14.2 Hz, 3J = 7.4 Hz, 3J = 4.7 Hz,
4J = 1.3 Hz, 1 H, H4b), 2.49 (dddd, 2J = 14.2 Hz, 3J = 8.7 Hz,
3J = 7.4 Hz, 4J = 1.3 Hz, 1 H, H4a), 4.15 (ddd, 2J = 12.3 Hz,
3J = 7.0 Hz, 4J = 1.1 Hz, 1 H, H1b), 4.22 (ddd, 2J = 12.3 Hz,
3J = 7.0 Hz, 4J = 1.1 Hz, 1 H, H1a), 4.35 (mc, 1 H, H5), 5.69
(ddddd, 3J = 11.0 Hz, 3J = 7.4 Hz, 3J = 7.4 Hz, 4J = 1.1 Hz,
4J = 1.1 Hz, 1 H, H3), 5.91 (ddddd, 3J = 11.0 Hz, 3J = 7.0 Hz,
3J = 7.0 Hz, 4J = 1.3 Hz, 4J = 1.3 Hz, 1 H, H2), 6.17 (dd,
3J = 15.9 Hz, 3J = 6.4 Hz, 1 H, H6), 6.58 (dd, 3J = 15.9 Hz,
4J = 1.3 Hz, 1 H, H7), 7.01 (dd, 3J = 8.7 Hz, 3J = 8.7 Hz, 2 H, H10),
7.35 (dd, 3J = 8.7 Hz, 4J = 5.3 Hz, 2 H, H9).
FT-IR (film): 3329, 2871, 1594, 1509, 1338, 1108, 971, 747 cm–1.
1H NMR (600 MHz, CDCl3): δ = 2.16 (br, 1 H, OH), 2.63 (br, 1 H,
OH), 2.46–2.54 (m, 2 H, H4a, H4b), 4.16 (ddd, 2J = 12.3 Hz,
3J = 6.9 Hz, 4J = 1.1 Hz, 1 H, H1a), 4.23 (ddd, 2J = 12.3 Hz,
3J = 7.1 Hz, 4J = 1.3 Hz, 1 H, H1b), 4.43 (dddd, 3J = 5.4 Hz,
3J = 5.4 Hz, 3J = 5.4 Hz, 4J = 1.7 Hz, 1 H, H5), 5.69 (ddddd,
13C NMR (151 MHz, CDCl3): δ = 35.3 (C4), 57.9 (C1), 71.5 (C5),
115.6 (d, 2J10,F = 21.4 Hz, C10), 128.0 (d, 3J9,F = 8.2 Hz, C9), 128.6
3
3
4
3J = 10.9 Hz, J = 7.8 Hz, J = 6.6 Hz, J = 1.1 Hz, 1 H, H3), 5.93
(ddddd, 2J = 10.9 Hz, 3J = 7.1 Hz, 3J = 6.9 Hz, 4J = 1.5 Hz,
4J = 1.3 Hz, 1 H, H2), 6.45 (dd, 3J = 15.9 Hz, 3J = 5.4 Hz, 1 H, H6),
6.71 (dd, 3J = 15.9 Hz, 4J = 1.7 Hz, 1 H, H7), 7.50 (d, 3J = 8.8 Hz,
2 H, H9), 8.20 (d, 3J = 8.8 Hz, 2 H, H10).
4
(C3), 129.5 (C7), 131.1 (C6), 131.9 (C2), 132.6 (d, J8,F = 3.3 Hz,
C8), 162.4 (d, 1J11,F = 247.0 Hz, C11).
MS (EI, 70 eV): m/z (%) = 204 (9, [(M – H2O)+]), 151 (100
[C9H8+FO+]), 149 (30, [C9H6FO+]), 133 (48, [C9H6F+]), 77 (13
[C6H5 ]).
13C NMR (151 MHz, CDCl3): δ = 35.2 (C4), 57.1 (C1), 70.8 (C5),
124.1 (C10), 127.0 (C9), 128.1 (C7), 128.4 (C2), 132.0 (C3), 136.5
(C6), 143.1 (C8), 147.0 (C11).
Anal. Calcd for C13H15FO2: C, 70.25; H, 6.80. Found: C, 70.28; H,
6.83.
MS (EI, 70 eV): m/z (%) = 231 (10, [M – H2+O]+), 178 (55, [(M –
(2Z,5S,6E)-7-(4-Fluorophenyl)hepta-2,6-diene-1,5-diol (ent-11)
According to general procedure A using allylboronic ester ent-4
(345 mg, 0.65 mmol) and 4-fluorocinnamaldehyde (23, 0.26 mL,
1.97 mmol); after 3 d, workup of the reaction followed by column
chromatography (CH2Cl2–MeOH, 95:5) gave ent-11 (136 mg,
95%) as a colorless oil; [α]D20 –79.0 (c 0.48, CHCl3); 97% ee. The
spectroscopic data are identical with those of diol 11.
C4H7O)+]), 132 (68, [C9H8O+]), 77 (70, [C6H5 ]).
Anal. Calcd for C13H15NO4: C, 62.64; H, 6.07. Found: C, 62.53; H,
6.09.
(2Z,5S,6E)-7-(4-Nitrophenyl)hepta-2,6-diene-1,5-diol (ent-13)
According to general procedure A using allylboronic ester 5
(320 mg, 0.60 mmol) and 4-nitrocinnamaldehyde (25, 318 mg,
1.80 mmol); after 3 d, workup of the reaction followed by column
chromatography (CH2Cl2–MeOH, 98:2) gave ent-13 (136 mg,
91%) as a colorless oil; [α]D20 –114.7 (c 1.00, CHCl3); 95% ee. The
spectroscopic data are identical with those of diol 13.
(2Z,5R,6E)-7-(2-Nitrophenyl)hepta-2,6-diene-1,5-diol (12)
According to general procedure A using allylboronic ester 4
(320 mg, 0.60 mmol) and 2-nitrocinnamaldehyde (24, 318 mg,
1.80 mmol); after 3 d, workup of the reaction followed by column
chromatography (CH2Cl2–MeOH, 98:2) gave 12 (139 mg, 93%) as
a colorless oil; 97% ee [HPLC (flow rate 0.5 mL/min, 20% i-PrOH–
Synthesis 2013, 45, 1106–1114
© Georg Thieme Verlag Stuttgart · New York

PAPER
Allylboronic Esters in Total Synthesis
1111
20
(2Z,5R)-Hex-2-ene-1,5-diol (6)
[α]D +1.0 (c 3.73, CHCl3); 93% ee. The spectroscopic data are
identical with those of diol 7.
According to general procedure A using allylboronic ester 5
(343 mg, 0.64 mmol) and acetaldehyde (19, 0.12 mL, 3.32 mmol);
after 3 d, workup of the reaction followed by column chromatogra-
phy (CH2Cl2–MeOH, 95:5) gave 6 (54 mg, 72%) as colorless oil;
99% ee [HPLC (flow rate 0.5 mL/min, 5% i-PrOH–heptane):
tR = 47.2 (ent-6), 44.5 min (6)]; Rf = 0.3 (CH2Cl2–MeOH, 95:5);
[α]D20 –15.0 (c 0.20, CHCl3).
(2Z,5R)-Dec-2-ene-1,5-diol (8)
According to general procedure A using allylboronic ester 5
(300 mg, 0.56 mmol) and hexanal (21, 0.20 mL, 1.68 mmol); after
3 d, workup of the reaction followed by column chromatography
(CH2Cl2–MeOH, 95:5) gave 8 (88 mg, 91%) as a colorless oil; 95%
ee [HPLC (flow rate 0.5 mL/min, 20% i-PrOH–heptane):
tR = 13.5 (8), 14.3 min (ent-8)]; Rf = 0.3 (CH2Cl2–MeOH, 95:5);
[α]D20 –3.0 (c 0.82, CHCl3).
FT-IR (film): 3313, 3017, 2968, 2921, 2875, 1737, 1653, 1374,
1125, 1075, 1044, 1006, 939, 843 cm–1.
3
1H NMR (600 MHz, CDCl3): δ = 1.24 (d, J = 6.2 Hz, 3 H, H6),
FT-IR (film): 3329, 2926, 2926, 2859, 1458, 1018 cm–1.
1.97 (br, 2 H, OH), 2.25 (dddd, 2J = 14.0 Hz, 3J = 8.7 Hz,
3J = 7.6 Hz, 4J = 1.4 Hz, 1 H, H4a), 2.31 (dddd, 2J = 14.0 Hz,
3J = 7.3 Hz, 3J = 4.3 Hz, 4J = 1.4 Hz, 1 H, H4b), 3.87 (dqd,
3J = 7.6 Hz, 3J = 6.2 Hz, 3J = 4.3 Hz, 1 H, H5), 4.13 (ddd,
2J = 12.3 Hz, 3J = 7.0 Hz, 4J = 1.3 Hz, 1 H, H1a), 4.21 (ddd,
2J = 12.3 Hz, 3J = 7.0 Hz, 4J = 1.3 Hz, 1 H, H1b), 5.65 (dddd,
3
1H NMR (600 MHz, CDCl3): δ = 0.90 (t, J = 7.0 Hz, 3 H, H10),
1.25–1.33 (m, 6 H, H7, H8, H9), 1.41–1.50 (m, 2 H, H6), 2.23–2.33
(m, 2 H, H4), 2.80 (br, 2 H, OH), 3.62–3.66 (m, 1 H, H5), 4.09 (ddd,
2J = 12.3 Hz, 3J = 6.8 Hz, 4J = 1.3 Hz, 1 H, H1a), 4.19 (ddd,
2J = 12.3 Hz, 3J = 7.4 Hz, 4J = 1.5 Hz, 1 H, H1b), 5.64 (ddddd,
3J = 11.1 Hz, 3J = 8.6 Hz, 3J = 7.3 Hz, 4J = 1.3 Hz, 4J = 1.3 Hz,
1 H, H3), 5.87 (ddddd, 3J = 11.1 Hz, 3J = 7.4 Hz, 3J = 6.8 Hz,
4J = 1.5 Hz, 4J = 1.5 Hz, 1 H, H2).
3
3
4
3J = 11.0 Hz, J = 8.7 Hz, J = 7.3 Hz, J = 1.3 Hz, 1 H, H3), 5.88
(ddddd, 3J = 11.0 Hz, 3J = 7.0 Hz, 3J = 7.0 Hz, 4J = 1.4 Hz,
3J = 1.4 Hz, 1 H, H2).
13C NMR (151 MHz, CDCl3): δ = 14.0 (C10), 22.6 (C7), 25.4 (C8),
31.8 (C9), 35.0 (C4), 37.1 (C6), 57.6 (C1), 70.7 (C5), 129.6 (C3),
131.3 (C2).
13C NMR (151 MHz, CDCl3): δ = 23.2 (C6), 36.8 (C4), 57.9 (C1),
66.6 (C5), 129.3 (C3), 131.5 (C2).
MS (EI, 70 eV): m/z (%) = 98 (6, [M – H2O]+), 83 (10, [(M –
MS (EI, 70 eV): m/z (%) = 83 (14, [(M – C3H9O)+]), 73 (8, [(M –
CH3O)+]), 69 (6, [(M – C2H7O)+]), 57 (12, [(M – C3H7O)+]), 54
C4H7O)+]), 71 (34 [(M – C4H9O)+]), 54 (100 [(M – C4H10O2)+]).
+
(100, [(M – C2H6O)2 ]).
FT-ICR-MS: m/z [M + Na]+ calcd for C10H20O2Na: 195.1361;
found: 195.1356.
FT-ICR-MS: m/z [M + Na]+ calcd for C6H12O2Na: 138.0735; found:
138.0730.
(2Z,5S)-Dec-2-ene-1,5-diol (ent-8)
(2Z,5S)-Hex-2-ene-1,5-diol (ent-6)
According to general procedure A using allylboronic ester 4
(354 mg, 0.66 mmol) and butanal (21, 0.25 mL, 2.77 mmol); after 3
d, workup of the reaction followed by column chromatography
(CH2Cl2–MeOH, 95:5) gave ent-8 (63 mg, 85%) as a colorless oil;
[α]D +1.4 (c 1.04, CHCl3); 94% ee. The spectroscopic data are
identical with those of diol 8.
According to general procedure A using allylboronic ester 4
(342 mg, 0.64 mmol) and acetaldehyde (19, 0.12 mL, 2.14 mmol);
after 3 d, workup of the reaction followed by column chromatogra-
phy (CH2Cl2–MeOH, 99:1) gave ent-6 (63 mg, 85%) as a colorless
oil; [α]D +19.0 (c 0.19, CHCl3); 98% ee. The spectroscopic data
are identical with those of diol 6.
20
20
(R)-Goniothalamin (1)
(2Z,5R)-Oct-2-ene-1,5-diol (7)
According to general procedure B using alcohol 9 (80 mg,
0.39 mmol), PhI(OAc)2 (650 mg, 1.98 mmol), and TEMPO (13 mg,
0.08 mmol) in CH2Cl2 (1.6 mL); after 1 d, workup of the reaction
and column chromatography (PE–EtOAc, 75:25) gave 1 (63 mg,
73%) as colorless solid; mp 83 °C; Rf = 0.2 (PE–EtOAc, 85:15);
[α]D20 +167.1 (c 0.21, CHCl3) [Lit.7 [α]D20 +169.8 (c 1.45, CHCl3)].
According to general procedure A using allylboronic ester 5
(233 mg, 0.44 mmol) and butanal (20, 0.17 mL, 1.89 mmol); after 3
d, workup of the reaction followed by column chromatography
(CH2Cl2–MeOH, 95:5) gave 7 (57 mg, 91%) as a colorless oil; 99%
ee [HPLC (flow rate 0.5 mL/min, 5% i-PrOH–heptane):
tR = 37.0 (7), 38.5 min (ent-7)]; Rf = 0.3 (CH2Cl2–MeOH, 95:5);
[α]D20 –3.0 (c 2.19, CHCl3).
FT-IR (film): 3028, 1722, 1494, 1383, 1245, 1058, 1021, 968, 814,
750, 695 cm–1.
FT-IR (film): 3335, 3017, 2958, 2926, 2870, 1738, 1366, 1217,
1010 cm–1.
1H NMR (600 MHz, CDCl3): δ = 2.53–2.56 (m, 2 H, H5), 5.11
(dddd, 3J = 9.1 Hz, 3J = 6.2 Hz, 3J = 6.2 Hz, 4J = 1.3 Hz, 1 H, H6),
6.10 (ddd, 3J = 9.8 Hz, 4J = 1.9 Hz, 4J = 1.9 Hz, 1 H, H3), 6.28 (dd,
3J = 15.9 Hz, 3J = 6.2 Hz, 1 H, H7), 6.73 (dd, 3J = 15.9 Hz,
4J = 1.3 Hz, 1 H, H8), 6.93 (ddd, 3J = 9.8 Hz, 3J = 4.9 Hz,
3
1H NMR (600 MHz, CDCl3): δ = 0.94 (t, J = 7.2 Hz, 3 H, H8),
1.32–1.52 (m, 4 H, H6, H7), 2.06 (br, 2 H, OH), 2.28 (m, 2 H, H4),
3.65–3.69 (m, 1 H, H5), 4.12 (ddd, 2J = 12.3 Hz, 3J = 6.9 Hz,
4J = 1.1 Hz, 1 H, H1a), 4.20 (ddd, 2J = 12.3 Hz, 3J = 7.1 Hz,
4J = 1.3 Hz, 1 H, H1b), 5.66 (ddddd, 3J = 11.0 Hz, 3J = 8.6 Hz,
3J = 7.5 Hz, 4J = 1.3 Hz, 4J = 1.1 Hz, 1 H, H3), 5.89 (ddddd,
3J = 11.0 Hz, 3J = 7.1 Hz, 3J = 6.9 Hz, 4J = 1.4 Hz, 4J = 1.4 Hz,
1 H, H2).
3
3J = 3.6 Hz, 1 H, H4), 7.28 (t, J = 7.4 Hz, 1 H, H12), 7.34 (dd,
3J = 7.4 Hz, 3J = 7.4 Hz, 2 H, H11), 7.40 (d, 3J = 7.4 Hz, 2 H, H10).
13C NMR (151 MHz, CDCl3): δ = 29.9 (C5), 78.0 (C6), 121.7 (C3),
125.7 (C7), 126.7 (C10), 128.4 (C12), 128.7 (C11), 133.2 (C8),
135.8 (C9), 144.6 (C4), 163.9 (C2).
13C NMR (151 MHz, CDCl3): δ = 14.0 (C8), 18.9 (C7), 35.0 (C4),
39.3 (C6), 57.8 (C1), 70.4 (C5), 129.5 (C3), 131.5 (C2).
MS (EI, 70 eV): m/z (%) = 200 (61, [M+]), 172 (27, [(M – CO)+]),
+
+
131 (28, [C9H7O+]), 115 (26), 104 (100, [C8H8 ]), 91 (42, [C7H7 ]),
77 (31, [C6H5 ]), 68 (93).
+
MS (EI, 70 eV): m/z (%) = 99 (27, [C5H7O2 ]), 83 (20, [C5H7O+]),
+
+
71 (34, [C5H11+]), 54 (100, [C4H6 ]).
The analytical data are in full agreement with the reported data.7,13
FT-ICR-MS: m/z [M + Na]+ calcd for C8H16O2Na: 167.1048; found:
167.1043.
(S)-Goniothalamin (ent-1)
According to general procedure B using alcohol ent-9 (100 mg,
0.49 mmol), PhI(OAc)2 (807 mg, 2.46 mmol), TEMPO (16 mg,
0.10 mmol) in CH2Cl2 (1.6 mL); after 1 d, workup of the reaction
and column chromatography (PE–EtOAc, 75:25) gave ent-1
(2Z,5S)-Oct-2-ene-1,5-diol (ent-7)
According to general procedure A using allylboronic ester 4
(354 mg, 0.66 mmol) and butanal (20, 0.25 mL, 2.77 mmol); after 3
d, workup of the reaction followed by column chromatography
(CH2Cl2–MeOH, 95:5) gave ent-7 (63 mg, 85%) as a colorless oil;
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 1106–1114

1112
S. Bartlett et al.
PAPER
20
(71 mg, 73%) as a colorless solid; [α]D –166.4 (c 0.19, CHCl3).
The spectroscopic data are identical with those of enantiomer 1.
(S)-6-[(E)-2-(4-Fluorophenyl)ethenyl]-5,6-dihydro-2H-pyran-
2-one (ent-16)
According to general procedure B using alcohol ent-11 (100 mg,
0.45 mmol), PhI(OAc)2 (740 mg, 2.25 mmol), and TEMPO (15 mg,
0.09 mmol) in CH2Cl2 (1.8 mL); after 3 d, workup of the reaction
followed by column chromatography (PE–EtOAc, 75:25) gave ent-
16 (76 mg, 77%) as a colorless solid; [α]D20 –160.1 (c 0.51, CHCl3)
(R)-6-[(E)-2-(4-Methoxyphenyl)ethenyl]-5,6-dihydro-2H-py-
ran-2-one (15)
According to general procedure B using alcohol 10 (100 mg,
0.43 mmol), PhI(OAc)2 (702 mg, 2.14 mmol), and TEMPO (14 mg,
0.09 mmol) in CH2Cl2 (1.8 mL); after 3 d, workup of the reaction
followed by column chromatography (PE–EtOAc, 75:25) gave 15
(51 mg, 52%) as a colorless solid; mp 102 °C; Rf = 0.4 (PE–EtOAc,
60:40); [α]D20 +140.5 (c 0.51, CHCl3).
25
[Lit.2f [α]D –158.0 (c 1.00, CHCl3)]. The spectroscopic data are
identical with those of enantiomer 16.
(R)-6-[(E)-2-(2-Nitrophenyl)ethenyl]-5,6-dihydro-2H-pyran-2-
one (17)
FT-IR (film): 2935, 1708, 1607, 1515, 1260, 1027, 969, 848,
812 cm–1.
According to general procedure B using alcohol 12 (111 mg,
0.45 mmol), PhI(OAc)2 (732 mg, 2.25 mmol), and TEMPO (14 mg,
0.09 mmol) in CH2Cl2 (1.9 mL); after 1 d, workup of the reaction
and column chromatography (PE–EtOAc, 75:25) gave 17 (85 mg,
78%) as a yellow solid; mp 78 °C; Rf = 0.3 (PE–EtOAc, 60:40);
[α]D20 +134.4 (c 1.01, CHCl3).
1H NMR (600 MHz, CDCl3): δ = 2.52–2.55 (m, 2 H, H5), 3.82 (s, 3
H, OCH3), 5.08 (dddd, 3J = 9.1 Hz, 3J = 6.6 Hz, 3J = 6.6 Hz,
4J = 1.3 Hz, 1 H, H6), 6.09 (ddd, 3J = 9.8 Hz, 4J = 1.9 Hz,
4J = 1.9 Hz, 1 H, H3), 6.14 (dd, 3J = 15.9 Hz, 3J = 6.6 Hz, 1 H, H7),
6.67 (dd, 3J = 15.9 Hz, 4J = 1.3 Hz, 1 H, H8), 6.87 (d, 3J = 8.7 Hz,
FT-IR (film): 3027, 2338, 1721, 1520, 1344, 1243, 1059, 1023, 964,
812 cm–1.
3
3
3
2 H, H11), 6.92 (ddd, J = 9.8 Hz, J = 4.5 Hz, J = 4.0 Hz, 1 H,
H4), 7.34 (d, 3J = 8.7 Hz, 2 H, H10).
1H NMR (600 MHz, CDCl3): δ = 2.55–2.65 (m, 2 H, H5), 5.16
(dddd, 3J = 10.2 Hz, 3J = 6.4 Hz, 3J = 5.1 Hz, 4J = 1.3 Hz, 1 H, H6),
6.11 (ddd, 3J = 9.9 Hz, 4J = 1.5 Hz, 4J = 1.3 Hz, 1 H, H3), 6.26 (dd,
3J = 15.9 Hz, 3J = 6.4 Hz, 1 H, H7), 6.95 (ddd, 3J = 9.9 Hz,
3J = 5.4 Hz, 3J = 3.0 Hz, 1 H, H4), 7.20 (dd, 3J = 15.9 Hz,
4J = 1.3 Hz, 1 H, H8), 7.46 (ddd, 3J = 8.2 Hz, 3J = 8.2 Hz,
4J = 1.7 Hz, 1 H, H12), 7.59–7.63 (m, 2 H, H13, H14), 7.99 (dd,
3J = 8.2 Hz, 4J = 1.7 Hz, 1 H, H11).
13C NMR (151 MHz, CDCl3): δ = 30.0 (C5), 55.3 (OCH3), 78.3
(C6), 114.1 (C11), 121.7 (C3), 123.4 (C7), 128.0 (C10), 128.5 (C9),
132.9 (C8), 144.6 (C4), 159.8 (C12), 164.0 (C2).
MS (EI, 70 eV): m/z (%) = 230 (73, [M+]), 202 (5, [(M – CO)+]),
+
185 (21, [(M – CHO2)+]), 162 (42), 161 (41, [C10H9O2 ]), 134 (100,
+
[C9H10O+]), 121 (41, [C8H9O+]), 91 (18, [C7H7 ]).
The analytical data are in full agreement with the reported data.2f,g
13C NMR (151 MHz, CDCl3): δ = 25.9 (C5), 77.5 (C6), 121.6 (C3),
124.7 (C11), 128.8 (C8), 128.9 (C12), 130.0 and 133.4 (C13, C14),
131.0 (C7), 131.8 (C9), 144.5 (C4), 147.8 (C10), 163.5 (C2).
(S)-6-[(E)-2-(4-Methoxyphenyl)ethenyl]-5,6-dihydro-2H-py-
ran-2-one (ent-15)
According to general procedure B using alcohol ent-10 (100 mg,
0.43 mmol), PhI(OAc)2 (702 mg, 2.14 mmol), and TEMPO (14 mg,
0.09 mmol) in CH2Cl2 (1.8 mL); after 3 d, workup of the reaction
followed by column chromatography (PE–EtOAc, 75:25) gave ent-
15 (51 mg, 52%) as a colorless solid; [α]D20 –141.7 (c 0.35, CHCl3)
+
MS (EI, 70 eV): m/z (%) = 97 (64, [C5H5O2 ]), 68 (100, C4H4O+).
Anal. Calcd for C13H11NO4: C, 63.67; H, 4.52. Found: C, 63.59; H,
4.56.
The analytical data are in full agreement with the reported data.10
25
[Lit.2f [α]D –133.7 (c 1.02, CHCl3)]. The spectroscopic data are
identical with those of enantiomer 15.
(S)-6-[(E)-2-(2-Nitrophenyl)ethenyl]-5,6-dihydro-2H-pyran-2-
one (ent-17)
(R)-6-[(E)-2-(4-Fluorophenyl)ethenyl]-5,6-dihydro-2H-pyran-
2-one (16)
According to general procedure B using alcohol ent-12 (120 mg,
0.48 mmol), PhI(OAc)2 (792 mg, 2.41 mmol), and TEMPO (16 mg,
0.10 mmol) in CH2Cl2 (2.0 mL); after 1 d, workup of the reaction
and column chromatography (PE–EtOAc, 75:25) gave ent-17
According to general procedure B using alcohol 11 (100 mg,
0.45 mmol), PhI(OAc)2 (740 mg, 2.25 mmol), and TEMPO (15 mg,
0.09 mmol) in CH2Cl2 (1.9 mL); after 3 d, workup of the reaction
followed by column chromatography (PE–EtOAc, 75:25) gave 16
(75 mg, 77%) as a colorless solid; mp 128 °C; Rf = 0.4 (PE–EtOAc,
60:40); [α]D20 +156.8 (c 0.49, CHCl3).
20
(70 mg, 59%) as a colorless solid; [α]D –128.6 (c 1.03, CHCl3).
The spectroscopic data are identical with those of enantiomer 17.
(R)-6-[(E)-2-(4-Nitrophenyl)ethenyl]-5,6-dihydro-2H-pyran-2-
one (18)
FT-IR (film): 3043, 2916, 1713, 1600, 1508, 1417, 1380, 1246,
1228, 1053, 1014, 972, 849, 821 cm–1.
According to general procedure B using alcohol 13 (95 mg,
0.38 mmol), PhI(OAc)2 (627 mg, 1.91 mmol), and TEMPO (12 mg,
0.08 mmol) in CH2Cl2 (1.6 mL); after 1 d, workup of the reaction
and column chromatography (PE–EtOAc, 75:25) gave 18 (74 mg,
80%) as a yellow solid; mp 125 °C; Rf = 0.3 (PE–EtOAc, 60:40);
[α]D20 +196.2 (c 1.03, CHCl3).
1H NMR (600 MHz, CDCl3): δ = 2.53–2.65 (m, 2 H, H5), 5.09
(dddd, 3J = 9.3 Hz, 3J = 6.3 Hz, 3J = 6.3 Hz, 4J = 1.3 Hz, 1 H, H6),
6.10 (ddd, 3J = 9.8 Hz, 4J = 2.3 Hz, 4J = 1.5 Hz, 1 H, H3), 6.19 (dd,
3J = 15.9 Hz, 3J = 6.3 Hz, 1 H, H7), 6.70 (dd, 3J = 15.9 Hz,
4J = 1.3 Hz, 1 H, H8), 6.93 (ddd, 3J = 9.8 Hz, 3J = 4.9 Hz,
3J = 3.6 Hz, 1 H, H4), 7.03 (dd, 3J = 8.7 Hz, 3J = 8.7 Hz, 2 H, H11),
7.37 (d, 3J = 8.7 Hz, 4J = 5.3 Hz, 2 H, H10).
FT-IR (film): 3032, 1721, 1594, 1509, 1340, 1246, 1107, 1089, 979,
822 cm–1.
1H NMR (600 MHz, CDCl3): δ = 2.55 (dddd, 2J = 18.3 Hz,
3J = 10.7 Hz, 3J = 2.8 Hz, 4J = 2.5 Hz, 1 H, H5a), 2.62 (dddd,
2J = 18.3 Hz, 3J = 5.7 Hz, 3J = 4.5 Hz, 4J = 1.2 Hz, 1 H, H5b), 5.17
(dddd, 3J = 10.7 Hz, 3J = 5.7 Hz, 3J = 4.5 Hz, 4J = 1.5 Hz, 1 H, H6),
6.12 (ddd, 3J = 9.7 Hz, 4J = 2.5 Hz, 4J = 1.2 Hz, 1 H, H3), 6.45 (dd,
3J = 15.9 Hz, 3J = 5.7 Hz, 1 H, H7), 6.84 (dd, 3J = 15.9 Hz,
4J = 1.5 Hz, 1 H, H8), 6.96 (ddd, 3J = 9.7 Hz, 3J = 5.7 Hz,
13C NMR (151 MHz, CDCl3): δ = 29.9 (C5), 77.8 (C6), 115.7 (d,
2J11,F = 21.7 Hz, C11), 121.7 (C3), 125.4 (C7), 128.3 (d, 3J10,F = 8.2
4
Hz, C10), 132.0 (d, J9,F = 3.4 Hz, C9), 132.0 (C8), 144.6 (C4),
162.7 (d, 1J12,F = 247.9 Hz, C12), 163.8 (C2).
MS (EI, 70 eV): m/z (%) = 218 (51 [M+]), 190 (31, [(M – CO)+]),
149 (24, [C9H6FO+]), 122 (100, [C8H7F+]), 68 (91, C4H2F+).
3
Anal. Calcd for C13H11FO2: C, 71.55; H, 5.08. Found: C, 71.38; H,
5.15.
3J = 2.8 Hz, 1 H, H4), 7.50 (d, J = 9.0 Hz, 2 H, H10), 8.20 (d,
3J = 9.0 Hz, 2 H, H11).
The analytical data are in full agreement with the reported data.2f
13C NMR (151 MHz, CDCl3): δ = 29.6 (C5), 77.0 (C6), 121.7 (C3),
124.1 (C11), 127.3 (C10), 130.2 (C7), 130.5 (C8), 142.4 (C9), 144.4
(C4), 147.4 (C12).
Synthesis 2013, 45, 1106–1114
© Georg Thieme Verlag Stuttgart · New York

PAPER
Allylboronic Esters in Total Synthesis
1113
MS (EI, 70 eV): m/z (%) = 245 (35 [M+]), 217 (31, [(M – CO)+]),
The analytical data are in full agreement with the reported data.11b
+
149 (24, [C8H7NO2 ]), 68 (100, C4H4O+).
(S)-6-Propyl-5,6-dihydro-2H-pyran-2-one (ent-14)
Anal. Calcd for C13H11NO4: C, 63.67; H, 4.52. Found: C, 63.59; H,
4.56.
The analytical data are in full agreement with the reported data.2f
According to general procedure B using alcohol 8 (71 mg,
0.49 mmol), PhI(OAc)2 (678 mg, 2.06 mmol), and TEMPO (14 mg,
0.17 mmol) in CH2Cl2 (1.8 mL); after 1 d, workup of the reaction
and column chromatography (PE–EtOAc, 75:25) gave ent-14
20
(S)-6-[(E)-2-(4-Nitrophenyl)ethenyl]-5,6-dihydro-2H-pyran-2-
one (ent-18)
(35 mg, 50%) as a colorless solid; [α]D +135.1 (c 1.66, CHCl3)
22
[Lit.11b [α]D +130.0 (c 1.20, CHCl3)]. The spectroscopic data are
According to general procedure B using alcohol ent-13 (100 mg,
0.40 mmol), PhI(OAc)2 (656 mg, 2.00 mmol), and TEMPO (13 mg,
0.08 mmol) in CH2Cl2 (1.7 mL); after 1 d, workup of the reaction
and column chromatography (PE–EtOAc, 75:25) gave ent-18
identical with those of enantiomer 14.
Massoia Lactone [(R)-6-Pentyl-5,6-dihydro-2H-pyran-2-one]
(3)
20
According to general procedure B using alcohol 8 (50 mg,
0.29 mmol), PhI(OAc)2 (636 mg, 1.94 mmol), and TEMPO (10 mg,
0.06 mmol) in CH2Cl2 (1.7 mL); after 1 d, workup of the reaction
and column chromatography (PE–EtOAc, 75:25) gave 3 (40 mg,
82%) as a colorless solid; Rf = 0.5 (PE–EtOAc, 70:30) [α]D20 –112.5
(c 0.65, CHCl3) [Lit.12 [α]D25 –115.6 (c 1.00, CHCl3)].
(76 mg, 77%) as a colorless solid; [α]D –191.6 (c 1.04, CHCl3)
25
[Lit.2f [α]D –205.0 (c 1.0, CHCl3)]. The spectroscopic data are
identical with those of enantiomer 18.
(S)-Parasorbic Acid [(S)-6-Methyl-5,6-dihydro-2H-pyran-2-
one] (2)
According to general procedure B using alcohol ent-6 (58 mg,
0.50 mmol), PhI(OAc)2 (823 mg, 2.50 mmol), and TEMPO (16 mg,
0.10 mmol) in CH2Cl2 (2.2 mL); after 1 d, workup of the reaction
and column chromatography (PE–EtOAc, 75:25) gave 2 (17 mg,
30%) as a colorless oil; [α]D20 +156.8 (c 0.49, CHCl3); Rf = 0.3 (PE–
EtOAc, 70:30).
FT-IR (film): 2931, 2861, 1712, 1467, 1386, 1248, 1037, 813 cm–1.
3
1H NMR (600 MHz, CDCl3): δ = 0.90 (t, J = 6.9 Hz, 3 H, H11),
1.28–1.35 (m, 4 H, H9, H10), 1.37–1.44 (m, 1 H, H8a), 1.49–1.55
(m, 1 H, H8b), 1.64 (dddd, 2J = 13.9 Hz, 3J = 10.4 Hz, 3J = 5.4 Hz,
3J = 5.2 Hz, 1 H, H7a), 1.80 (dddd, 2J = 13.9 Hz, 3J = 10.4 Hz,
3
3
3J = 7.4 Hz, J = 5.2 Hz, 1 H, H7b), 2.28–2.38 (m, 2 H, H5), 4.42
1H NMR (600 MHz, CDCl3): δ = 1.44 (d, J = 6.4 Hz, 3 H, H7),
(dddd, 3J = 10.4 Hz, 3J = 7.4 Hz, 3J = 5.4 Hz, 3J = 5.2 Hz, 1 H, H6),
6.02 (ddd, 3J = 9.8 Hz, 4J = 2.5 Hz, 4J = 1.3 Hz, 1 H, H3), 6.88
(ddd, 3J = 9.8 Hz, 3J = 5.5 Hz, 3J = 3.0 Hz, 1 H, H4).
2.30 (dddd, 2J = 18.3 Hz, 3J = 11.3 Hz, 4J = 2.6 Hz, 3J = 2.6 Hz,
1 H, H5a), 2.37 (dddd, 2J = 18.3 Hz, 4J = 5.9 Hz, 3J = 4.2 Hz,
3J = 1.1 Hz, 1 H, H5b), 4.57 (dqd, 3J = 11.3 Hz, 3J = 6.4 Hz,
3J = 4.2 Hz, 1 H, H6), 6.03 (ddd, 3J = 9.7 Hz, 3J = 2.6 Hz,
3J = 1.1 Hz, 1 H, H4), 6.87 (ddd, 3J = 9.7 Hz, 4J = 5.9 Hz,
4J = 2.6 Hz, 1 H, H3).
13C NMR (151 MHz, CDCl3): δ = 14.0 (C11), 22.5 (C10), 24.5
(C8), 29.4 (C5), 31.6 (C9), 34.8 (C7), 78.0 (C6), 121.5 (C3), 145.0
(C4), 164.6 (C2).
13C NMR (151 MHz, CDCl3): δ = 20.8 (C7), 31.0 (C5), 74.4 (C6),
121.4 (C3), 144.9 (C4), 164.6 (C2).
MS (EI, 70 eV): m/z (%) = 97 (100, [(M – C5H11)+]), 68 (90, [(M –
C6H12O)+]).
The analytical data are in full agreement with the reported data.4a,11
The analytical data are in full agreement with the reported data.12
(R)-6-Methyl-5,6-dihydro-2H-pyran-2-one (ent-2)
(S)-6-Pentyl-5,6-dihydro-2H-pyran-2-one (ent-3)
According to general procedure B using alcohol 6 (41 mg,
0.29 mmol), PhI(OAc)2 (397 mg, 1.21 mmol), and TEMPO (8 mg,
0.05 mmol) in CH2Cl2 (1.1 mL); after 1 d, workup of the reaction
and column chromatography (PE–EtOAc, 75:25) gave ent-2
(16 mg, 39%) as a colorless oil; [α]D20 –160.1 (c 0.51, CHCl3). The
spectroscopic data are identical with those of enantiomer 2.
According to general procedure B using alcohol ent-8 (46 mg,
0.27 mmol), PhI(OAc)2 (581 mg, 1.77 mmol), and TEMPO (10 mg,
0.06 mmol) in CH2Cl2 (1.7 mL); after 1 d, workup of the reaction
and column chromatography (PE–EtOAc, 75:25) gave ent-3
(44 mg, 98%) as a colorless oil; [α]D20 +113.1 (c 0.65, CHCl3). The
spectroscopic data are identical with those of enantiomer 3.
(R)-6-Propyl-5,6-dihydro-2H-pyran-2-one (14)
According to general procedure B using alcohol ent-7 (71 mg,
0.49 mmol), PhI(OAc)2 (678 mg, 2.06 mmol), and TEMPO (14 mg,
0.17 mmol) in CH2Cl2 (1.8 mL); after 1 d, workup of the reaction
and column chromatography (PE–EtOAc, 75:25) gave 14 (35 mg,
50%) as a colorless solid; Rf = 0.5 (PE–EtOAc, 70:30); [α]D
–109.1 (c 0.63, CHCl3).
Acknowledgment
We acknowledge gratefully the Fonds der Chemischen Industrie
(scholarship to D.B.), the Deutsche Forschungs-gemeinschaft
(DFG PI 263/5-1), the DAAD (RISE-scholarship for S.B.) the Mi-
nistry of Innovation, Science, and Research of the German federal
state of North Rhine-Westphalia, the Heinrich-Heine-Universität
Düsseldorf and the Forschungszentrum Jülich GmbH for their ge-
nerous support of our projects. Furthermore, we thank the analytical
departments of the Forschungszentrum Jülich as well as Marvin
Lübcke, Monika Gehsing, Rainer Goldbaum, Birgit Henßen, Erik
Kranz, Vera Ophoven, Bea Paschold, Truc Pham, Dagmar
Drobietz, and Saskia Schuback for their ongoing support.
20
FT-IR (film): 2960, 2931, 2875, 2298, 1716, 1467, 1421, 1386,
1245, 1158, 1114, 1069, 1028, 960, 920, 814, 743, 662 cm–1.
3
1H NMR (600 MHz, CDCl3): δ = 0.96 (t, J = 7.3 Hz, 3 H, H9),
1.45 (ddqd, 2J = 14.5 Hz, 3J = 10.2 Hz, 3J = 7.3 Hz, 3J = 5.8 Hz,
1 H, H8a), 1.55 (ddqd, 2J = 14.5 Hz, 3J = 10.0 Hz, 3J = 7.3 Hz,
3J = 5.2 Hz, 1 H, H8b), 1.62 (dddd, 2J = 13.7 Hz, 3J = 10.0 Hz,
3J = 5.8 Hz, 3J = 5.3 Hz, 1 H, H7a), 1.80 (dddd, 2J = 13.7 Hz,
3J = 10.2 Hz, 3J = 7.5 Hz, 3J = 5.2 Hz, 1 H, H7b), 2.28–2.38 (m,
2 H, H5), 4.44 (dddd, 3J = 10.3 Hz, 3J = 7.5 Hz, 3J = 5.3 Hz,
3J = 5.1 Hz, 1 H, H6), 6.02 (ddd, 3J = 9.7 Hz, 4J = 2.5 Hz,
4J = 1.3 Hz, 1 H, H3), 6.88 (ddd, 3J = 9.7 Hz, 3J = 5.5 Hz,
3J = 2.8 Hz, 1 H, H4).
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnoIufproi
m
tgioSrantnugIifoop
r
itmnatr
13C NMR (151 MHz, CDCl3): δ = 13.8 (C9), 18.1 (C8), 29.4 (C5),
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© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 1106–1114

1114
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Synthesis 2013, 45, 1106–1114
© Georg Thieme Verlag Stuttgart · New York