Relay catalytic cascade hydrosiloxylation and asymmetric hetero-diels-alder reaction

Article abstract of DOI:10.1055/s-0033-1340905

The hybrid gold(I)/Bronsted acid binary catalyst system enables enynes to participate in an asymmetric relay catalytic cascade intramolecular hydrosiloxylation and asymmetric hetero-Diels-Alder reaction with fluorenyl glyoxylate. Georg Thieme Verlag Stutt

Full text of DOI:10.1055/s-0033-1340905

SPECIAL TOPIC
▌1355
sRpeecilalatoypicCatalytic Cascade Hydrosiloxylation and Asymmetric Hetero-
Diels–Alder Reaction
Synthesis of 1,2-Oxasiline-Fused Pyrans
Nan Li, Dian-Feng Chen, Pu-Sheng Wang, Zhi-Yong Han, Liu-Zhu Gong*
Hefei National Laboratory for Physical Sciences at the Microscale and Department of Chemistry, University of Science and Technology of China,
Hefei 230026, P. R. of China
Fax +86(551)3606266; E-mail: gonglz@ustc.edu.cn
Received: 27.01.2014; Accepted after revision: 12.02.2014
reaction with quinones9 and Mukaiyama aldol reaction
Abstract: The hybrid gold(I)/Brønsted acid binary catalyst system
with glyoxylates,10 respectively (Scheme 1, equations 1
enables enynes to participate in an asymmetric relay catalytic cas-
and 2). As our interest continues in the asymmetric relay
cade intramolecular hydrosiloxylation and asymmetric hetero-
catalysis, we now report a cascade intermolecular hydro-
siloxylation and oxo-hetero-Diels–Alder reaction of [2-
(but-3-en-1-ynyl)phenyl]diphenylsilanol derivatives with
glyoxylates (Scheme 1, equation 3).
Diels–Alder reaction with fluorenyl glyoxylate.
Key words: Diels–Alder reaction, enantioselectivity, silicon, het-
erocycles, enynes
Terada and co-workers have previously demonstrated that
chiral phosphoric acids could effectively catalyze the oxo-
hetero-Diels–Alder reaction of glyoxylates with dienes.4d
We have found that the cationic gold(I) complexes were
able to effect intramolecular hydrosiloxylation to generate
dienes.9 Therefore, we initially investigated the cascade
reaction of enynyldiethylsilanol 1a with fluorenyl glyox-
ylate 210 in the presence of the gold complex 3 alone. Un-
fortunately, the desired cascade reaction was not observed
and a diene generated from the gold-catalyzed intermolec-
ular hydrosiloxylation was isolated (Table 1, entry 1).11
The use of the combined gold complex 312 and 4a was also
unable to promote the cascade reaction (entry 2). The ad-
dition of the phosphoric acid 4b bearing two bulkier sub-
stituents as a chiral co-catalyst led to trace amount of
product (entry 3). To our delight, the use of chiral N-triflyl
phosphoramide 4c,13 in combination of gold complex 3,
was able to afford the cascade reaction although the de-
sired adduct 5a was isolated in 15% yield with moderate
enantioselectivity (entry 4). Interestingly, the addition of
either anhydrous magnesium or sodium sulfate as an addi-
tive enhanced the yield and maintained enantioselectivity
(entries 5 and 6). The enynyldiphenylsilanol 1b gave an
even better result in terms of the yield and stereochemical
outcome (entry 7). Then, we screened a variety of struc-
turally diverse chiral N-triflyl phosphoramides 4d–h de-
rived from 3,3′-disubstituted 1,1′-bi-2-naphthols
(BINOLs) for the reaction and found that chiral N-triflyl
phosphoramide 4h was the optimal catalyst giving the cy-
clic product 5b in 70% yield and 86% ee (entries 8–12).
In addition, various solvents were investigated for the re-
action; nonpolar solvents were more suitable media and,
in particular, toluene was the solvent of choice in terms of
both the yield and enantioselectivity (entries 12–16). Sig-
nificantly, the loading of gold complex 3 could be reduced
to as little as 1 mol% without diminishing the reaction ef-
ficiency (entry 17).
The hetero-Diels–Alder reaction (HDA) is one of the most
important transformations for the synthesis of six-mem-
bered heterocycles, which are commonly found in natural
products and unnatural biologically active molecules;1 it
has received a great deal of research interest over a long
period.2 The asymmetric oxo-hetero-Diels–Alder of 2-si-
loxy-1,3-dienes with aldehydes gives directly chiral dihy-
dropyranone derivatives, which have been widely applied
in the total synthesis of a diverse spectrum of natural prod-
ucts as key intermediates, stands out in particular for its
importance and it has been intensely investigated.3,4 The
2-siloxy-1,3-dienes exploited in the asymmetric hetero-
Diels–Alder reaction were preformed from enolizable car-
bonyls, wherein a stoichiometric or more amount of
strong base was required. In contrast, the use of in situ
generated 2-siloxy-1,3-dienes for the asymmetric hetero-
Diels–Alder reaction avoids additional workup and puri-
fication processes associated with the classical methods
and, therefore, is unarguably more interesting. However,
this protocol has been much less explored.
The robust capability of gold complexes in the activation
of the carbon–carbon triple bond allowed the emergence
of numerous nucleophilic addition reactions of heteroat-
oms to alkynes and enynes, leading to the generation of
functionalized compounds that could participate in a di-
verse range of transformations.5 More interestingly, the
gold complexes are highly compatible with Brønsted
acids allowing the design of relay catalytic asymmetric re-
actions.6,7 In recent years, we have established a range of
asymmetric relay catalytic cascade reactions by using hy-
brid gold/chiral phosphoric acid binary catalyst sys-
tems.7c,8 Very recently, we demonstrated that the
gold(I)/Brønsted acid binary catalyst enabled enynes and
alkynes to act as latent 1,3-siloxydienes and silyl enol
ethers to undergo a highly enantioselective Diels–Alder
Under the optimized reaction conditions, the generality of
this reaction for enynes was then explored (Scheme 2). To
our delight, the asymmetric relay catalytic reaction toler-
SYNTHESIS 2014, 46, 1355–1361
Advanced online publication: 17.03.2014
DOI: 10.1055/s-0033-1340905; Art ID: SS-2014-C0068-OP
© Georg Thieme Verlag Stuttgart · New York
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X

1356
N. Li et al.
SPECIAL TOPIC
previous work:
R2
[L1AuNCMe]+SbF6
(6 mol%)
–
O
R1
O
O
R1
R2
B*H-1 (15 mol%)
O
R3
(1)
+
OH
Si
PhF, r.t.
R3
R4 R4
O
Si
R4
R4
O
R2
R2
L2AuMe (5 mol%)
B*H-2 (15 mol%)
O
CO2R3
(2)
HO
R1
OR3
+
R1
OH
toluene, 25 °C, 36 h
O
Si
OH
Si
Me Me
Me
Me
Ar
O
O
P
N
N
Ar
Ar
O
NHTf
t-Bu
t-Bu
P
L2 Ar = 2,6-(i-Pr)2C6H3
Ar
B*H-1 Ar = 1-pyrenyl
B*H-2 Ar = 2,4,6-(i-Pr)3C6H2
L1
this work: hetero-Diels–Alder reaction:
R2
OR5
O
R1
O
O
R1
(3)
Au(I)/B*-H
R3
R2
HO
OR5
+
R3
OH
Si
R4 R4
O
OH
Si
R4
R4
Scheme 1 Gold(I)-catalyzed hydrosiloxylation and related cascade reactions
ated a wide spectrum of enynyldiphenylsilanols bearing 63% yield, but with only 2:1 diastereomeric ratio and
either an electron-donating or -withdrawing aryl substitu- moderate enantioselectivities of 67% and 45% ee, respec-
ent, giving the desired compounds 5c and 5d in moderate tively. However, if a phenyl substituent was introduced at
yields and enantioselectivities. The enynyldiphenylsilan- C4 of the enyne, the desired hetero-Diels–Alder adduct
ols with an alkyl or phenyl substituent at C3 underwent was not observed. The configuration of 5g was deter-
the cascade reaction cleanly, furnishing the desired prod- mined by X-ray crystallographic analysis (Figure 1).
ucts 5e–i in moderate yields (50–73%) and with high lev-
In the presence of triethylamine, the cyclic compound 5b
els of diastereo- and enantioselectivities (up to >20:1 dr
obtained from the relay catalytic cascade reaction could
and 93% ee). Surprisingly, the enynyldiphenylsilanol 1j
be transformed into an anti-disubstituted cyclohexanone
with a methyl substituent at C4 provided the product 5j in
Figure 1 X-ray crystal structure of 5g
Synthesis 2014, 46, 1355–1361
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
Synthesis of 1,2-Oxasiline-Fused Pyrans
1357
Table 1 Catalyst Screening and Optimization of the Reaction Conditionsa
OH
O
Au(I) cat. 3 (6 mol%)
OFlu
O
R
R
4 (15 mol%)
+
OH
R
HO
Flub
Si
Si
O
toluene, additive, 35 °C
O
O
R
1a R = Et
1b R = Ph
2
5a R = Et
5b R = Ph
–
SbF6
Ar
4a X = O, Ar = Ph
4b X = O, Ar = 9-anthracenyl
N
N
Ar
Ar
4c X = NTf, Ar = 9-anthracenyl
4d X = NTf, Ar = 1-pyrenyl
O
O
O
Au
N
P
4e X = NTf, Ar = 4-O2NC6H4
4f X = NTf, Ar = 2,4,6-(i-Pr)3C6H2
XH
4g X = NTf, Ar = 2,6-(i-Pr)2, 4-(t-Bu)C6H2
4h X = NTf, Ar = 2,4,6-(Cy)3C6H2
Ar
Me
3 Ar = 2,6- (i-Pr)2C6H3
Entry
R
4
Additive
Yieldc (%)
eed (%)
e
1
2
Et
–
–
–
–
e
Et
4a
4b
4c
4c
4c
4c
4d
4e
4f
–
–
–
3
Et
–
trace
15
–
4
Et
–
60
60
60
62
–
5
Et
MgSO4
Na2SO4
Na2SO4
Na2SO4
Na2SO4
Na2SO4
Na2SO4
Na2SO4
Na2SO4
Na2SO4
Na2SO4
Na2SO4
Na2SO4
23
6
Et
30
7
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
48
e
8
–
e
9
–
–
10
11
12
13
14
15
16
17
45
64
70
58
70
60
62
70
77
74
86
80f
83g
86h
84i
86j
4g
4h
4h
4h
4h
4h
4h
a Unless indicated otherwise, reaction conditions: 1 (0.1 mmol), 2 (0.2 mmol), gold catalyst 3 (6 mol%), Brønsted acid 4 (15 mol%), additive
(50 mg), toluene (2 mL), 35 °C.
b Flu = 9H-fluoren-9-yl.
c Isolated yield.
d The ee was determined by HPLC.
e The desired product was not obtained.
f In CH2Cl2.
g In CHCl3.
h In PhF.
i In DCE.
j 1 mol% of 3 was used.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 1355–1361

1358
N. Li et al.
SPECIAL TOPIC
R2
3
FluO2C
O
R1
R2
2
Au(I) cat. 3 (1 mol%)
4h (15 mol%)
1
OH
4
R1
OFlu
R3
R3
toluene, Na2SO4, 35 °C
+
HO
O
OH
Ph
Si
O
Si
Ph
Ph
Ph
2
1
5
FluO2C
O
FluO2C
O
FluO2C
O
FluO2C
O
MeO
MeO
Ph
n-Bu
O
O
O
O
F
Si
Si
Si
Si
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
5e
5f
5c
5d
yield = 50%
ee = 87%
dr = 6:1
yield = 59%
ee = 87%
dr = 5:1
yield = 72%
ee = 78%
yield = 66%
ee = 86%
FluO2C
O
FluO2C
O
FluO2C
O
Me
FluO2C
O
O
Me
n-Pr
Me
Me
2
O
O
O
Si
Si
Si
Si
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
5g
5h
5i
5j
yield = 73%
ee = 88%
dr = 13:1
yield = 66%
ee = 88%
dr = 10:1
yield = 68%
ee = 93%
dr >20:1
yield = 63%
ee = 67%, 45%
dr = 2:1
Scheme 2 Generality of the reaction. Reagents and conditions: 1 (0.1 mmol), 2 (0.2 mmol), gold catalyst 3 (1 mol%), Brønsted acid 4h (15
mol%), anhyd Na2SO4 (50 mg), toluene (2 mL), 35 °C; dr was determined from the 1H NMR spectra of the crude reaction mixture.
derivative 6 in methanol in 80% yield and almost main-
taining the enantiomeric excess (Scheme 3).
NMR spectra were recorded on a Bruker 400 MHz spectrometer.
FT-ICRMS spectra were recorded on P-SIMS-Gly of Bruker Dal-
tonics Inc. IR spectra were recorded on a Nicolet MX-1E FT-IR
spectrophotometer. HPLC analysis was performed on Waters-
Breeze (2487 dual absorbance detector and 1525 binary HPLC
pump, UV detection: 254nm) and Agilent 1200. Chiralpak AD, IC,
and IA columns were purchased from Daicel Chemical Industries,
O
O
Ltd. The absolute configuration of 5g was assigned by X-ray anal-
ysis. Analytical grade solvents for the column chromatography and
commercially available reagents were used as received. DCE,
MeCN, and CH2Cl2 were dried over CaH2 and distilled prior to use.
Toluene, THF, and Et2O were dried over Na and distilled prior to
use. The gold complex14 and Brønsted acid catalysts15 were pre-
pared following the literature report. The substrates9 and fluorenyl
glyoxylate10 were synthesized according to the literature.
O
O
O
Et3N (1.5 equiv)
MeOH, r.t.
O
O
OMe
O
Si
Si
Ph
Ph
Ph
Ph
6
5b
80% yield
82% ee
86% ee
[2-(But-3-en-1-ynyl)-5-fluorophenyl]diphenylsilanol (1c)
Isolated as a light yellow oil; yield: 492 mg (1.43 mmol, 77%).
Scheme 3
IR (KBr): 3383, 3081, 2971, 2861, 1733, 1587, 1468, 1267, 1207,
1168, 854, 634, 506 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.73–7.32 (m, 11 H), 7.16–6.99
(m, 2 H), 5.70 (dd, J = 17.4, 11.3 Hz, 1 H), 5.37 (dd, J = 11.3, 2.0
Hz, 1 H), 5.26 (dd, J = 17.4, 1.9 Hz, 1 H), 3.05 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 162.1 (d, J = 162 Hz, 1 C), 136.4,
136.0, 134.4, 134.2, 134.1, 130.3, 129.8, 127.9, 127.9, 127.5, 116.3,
91.5, 90.4.
In summary, we have established an unprecedented relay
catalytic cascade intramolecular hydrosiloxylation and
asymmetric hetero-Diels–Alder reaction between enynyl-
diphenylsilanols and fluorenyl glyoxylate. The 3,3′-
bis(2,4,6-tricyclohexylphenyl)-BINOL-based phosphor-
amide showed the highest stereochemical control. A wide
range of enynyldiphenylsilanols were able to participate HRMS (ESI): m/z [M + Na]+ calcd for C22H17FNaOSi: 367.09249;
found: 367.09206.
in the relay catalytic cascade reaction, leading to genera-
tion of 3,6-dihydropyran derivatives in fairly good yields
and with high levels of enantioselectivity.
[2-(But-3-en-1-ynyl)-4,5-dimethoxyphenyl]diphenylsilanol (1d)
Isolated as a yellow oil; yield: 539 mg (1.48 mmol, 81%).
Synthesis 2014, 46, 1355–1361
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
Synthesis of 1,2-Oxasiline-Fused Pyrans
1359
IR (KBr): 3512, 3081, 3017, 2952, 2192, 1585, 1493, 1322, 1257,
1110, 1056, 845, 698 cm–1.
127.8, 127.8, 126.0, 125.9, 125.7, 121.4, 120.0, 119.9, 107.3, 75.7,
74.3, 62.0, 30.0.
1H NMR (400 MHz, CDCl3): δ = 7.88–7.41 (m, 10 H), 7.14 (s, 1 H),
7.10 (s, 1 H), 5.79 (dd, J = 17.2, 11.4 Hz, 1 H), 5.43 (d, J = 11.0 Hz,
1 H), 5.33 (d, J = 17.5 Hz, 1 H), 3.99 (s, 3 H), 3.84 (s, 3 H), 3.39 (s,
1 H).
13C NMR (100 MHz, CDCl3): δ = 150.1, 148.8, 135.2, 135.0, 130.6,
129.9, 127.8, 126.7, 121.4, 118.2, 116.6, 115.3, 91.5, 90.6, 55.8,
55.7.
HRMS (ESI): m/z [M + Na]+ calcd for C37H28O4NaSi: 587.16491;
found: 587.16415.
9H-Fluoren-9-yl (S)-8-Fluoro-6,6-diphenyl-1,3,4,6-tetrahydro-
benzo[c]pyrano[3,4-e][1,2]oxasiline-1-carboxylate (5c)
20
Isolated as a colorless oil; yield: 41.9 mg (0.072 mmol, 72%); [α]D
–5.1 (c 0.312, CHCl3); 78% ee [HPLC (Chiracel-IC-H, hexane–
i-PrOH, 90:10, flow rate 1.0 mL/min, T = 30 °C, 254 nm): tR = 8.06
(minor), 9.12 min (major)]; the absolute configuration was tenta-
tively assigned by analogy.
HRMS (ESI): m/z [M + H]+ calcd for C24H23FO3Si: 387.14110;
found: 387.14081.
IR (KBr): 3439, 2932, 1733, 1429, 1192, 1120, 999, 743, 698, 504
cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.79–6.92 (m, 21 H), 6.80 (s, 1 H),
5.38 (s, 1 H), 4.39–4.19 (m, 1 H), 4.05–3.88 (m, 1 H), 2.81–2.58 (m,
1 H), 2.47–2.29 (m, 1 H).
[2-(6-Methyl-3-methylenehept-1-ynyl)phenyl]diphenylsilanol
(1h)
Isolated as a yellow oil; yield: 576 mg (1.54 mmol, 86%).
IR (KBr): 3512, 3429, 3090, 3035, 2952, 1477, 1449, 1120, 1056,
836, 772, 698, 506 cm–1.
13C NMR (100 MHz, CDCl3): δ = 171.6, 160.7 (d, J = 249.4 Hz, 1
C), 159.5, 148.9, 141.6, 141.4, 141.1, 141.0, 136.48, 135.7, 135.7,
135.2, 135.0, 134.2, 132.3, 131.8, 131.0, 130.9, 129.8, 129.6, 129.5,
129.0, 128.9, 128.2, 128.1, 128.0, 127.9, 127.8, 125.9, 125.6, 123.7,
123.6, 120.2, 120.0, 120.0, 117.7, 117.5, 106.9, 75.8, 74.2, 62.0,
29.8.
1H NMR (400 MHz, CDCl3): δ = 7.63–7.12 (m, 14 H), 5.04 (d,
J = 1.6 Hz, 1 H), 4.90 (d, J = 2.0 Hz, 1 H), 3.14 (s, 1 H), 1.94–1.79
(m, 2 H), 1.43–1.33 (m, 1 H), 1.19–1.12 (m, 2 H), 0.74 (d, J = 3.2
Hz, 6 H).
13C NMR (100 MHz, CDCl3): δ = 138.0, 136.1, 135.2, 134.9, 132.5,
131.4, 130.0, 129.9, 128.5, 127.9, 127.8, 127.6, 121.6, 93.9, 90.3,
37.2, 34.6, 27.4, 22.5.
HRMS (ESI): m/z [M + Na]+ calcd for C37H27O4FNaSi: 605.15549;
found: 605.15527.
HRMS (ESI): m/z [M + H]+ calcd for C27H29OSi: 397.19822; found:
397.19753.
9H-Fluoren-9-yl (S)-8,9-Dimethoxy-6,6-diphenyl-1,3,4,6-tetra-
hydrobenzo[c]pyrano[3,4-e][1,2]oxasiline-1-carboxylate (5d)
Isolated as a yellow oil; yield: 41.2 mg (0.066 mmol, 66%);
[α]D20–5.5 (c 0.35, CHCl3); 86% ee [HPLC (Chiracel-IC-H, hexane–
i-PrOH, 70:30, flow rate 1.0 mL/min, T = 30 °C, 254 nm): tR = 6.63
(minor), 7.20 min (major)]; the absolute configuration was tenta-
tively assigned by analogy.
[(Z)-2-(Pent-3-en-1-ynyl)phenyl]diphenylsilanol (1j)
Isolated as a yellow oil; yield: 477 mg (1.50 mmol, 85%).
IR (KBr): 3357, 3050, 2962, 2921, 1431, 1110, 836, 744, 698, 506
cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.71–7.22 (m, 14 H), 5.92 (dq,
J = 10.8, 6.9 Hz, 1 H), 5.44 (dd, J = 10.7, 1.7 Hz, 1 H), 3.21 (s, 1 H),
1.63 (dd, J = 6.9, 1.6 Hz, 3 H).
IR (KBr): 3071, 2932, 2852, 2247, 1731, 1630, 1503, 1447, 1365,
1256, 907, 714, 494 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.79–7.09 (m, 18 H), 6.90 (s, 1 H),
6.79 (s, 1 H), 6.66 (s, 1 H), 5.40 (s, 1 H), 4.36–4.29 (m, 1 H), 4.00–
3.94 (m, 1 H), 3.78 (s, 3 H), 3.41 (s, 3 H), 2.78–2.54 (m, 1 H), 2.48–
2.29 (m, 1 H).
13C NMR (100 MHz, CDCl3): δ = 171.9, 151.0, 148.3, 147.3, 141.6,
141.4, 141.0, 141.0, 135.2, 135.1, 133.9, 133.4, 133.0, 130.7, 130.7,
129.6, 129.5, 128.1, 128.0, 127.9, 127.9, 126.1, 125.7, 120.0, 120.0,
117.1, 115.7, 106.8, 105.8, 75.9, 74.2, 62.0, 56.0, 55.3, 29.8.
13C NMR (100 MHz, CDCl3): δ = 140.6, 139.4, 136.0, 135.1, 134.2,
132.5, 132.1, 130.0, 129.8, 127.9, 127.8, 127.3, 95.2, 92.3, 18.8.
HRMS (ESI): m/z [M + H]+ calcd for C23H21OSi: 341.13562; found:
341.13540.
9H-Fluoren-9-yl (S)-6,6-Diphenyl-1,3,4,6-tetrahydroben-
zo[c]pyrano[3,4-e][1,2]oxasiline-1-carboxylates 5b–j; General
Procedure
To a solution of gold complex 3 (1 mol%), N-triflyl phosphoramide
4h (15 mol%), fluorenyl glyoxylate 2 (0.2 mmol), and Na2SO4 (50
mg) in toluene (1 mL) was added a solution of enynylsilanol 1 (0.1
mmol) in toluene (1 mL) in one portion under argon. The resulting
mixture was stirred at 35 °C for 6 d, and then the mixture was di-
rectly subjected to flash column chromatography (silica gel,
EtOAc–petroleum ether) to afford product 5.
HRMS (ESI): m/z [M + Na]+ calcd for C39H32O6NaSi: 647.18604;
found: 647.18604.
9H-Fluoren-9-yl (1S,4R)-4,6,6-Triphenyl-1,3,4,6-tetrahydro-
benzo[c]pyrano[3,4-e][1,2]oxasiline-1-carboxylate (5e)
Isolated as a yellow oil; yield: 32.1 mg (0.05 mmol, 50%); [α]D
20
–21.1 (c 0.32, CHCl3); 87% ee [HPLC (Chiracel-IC-H, hexane–
i-PrOH, 90:10, flow rate 1.0 mL/min, T = 30 °C, 254 nm): tR = 6.08
(minor), 6.58 min (major)]; the absolute configuration was tenta-
tively assigned by analogy.
9H-Fluoren-9-yl (S)-6,6-Diphenyl-1,3,4,6-tetrahydroben-
zo[c]pyrano[3,4-e][1,2]oxasiline-1-carboxylate (5b)
20
Isolated as a yellow oil; yield: 39.5 mg (0.07 mmol, 70%); [α]D
–15.1 (c 0.44, CHCl3); 86% ee [HPLC (Chiracel-IC-H, hexane–
i-PrOH, 90:10, flow rate 1.0 mL/min, T = 30 °C, 254 nm): tR = 6.24
(minor), 7.34 min (major)]; the absolute configuration was tenta-
tively assigned by analogy.
IR (KBr): 3053, 2923, 1732, 1632, 1429, 1361, 1193, 1135, 912,
697, 513 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.74–6.86 (m, 27 H), 6.85 (s, 1 H),
5.61 (d, J = 1.3 Hz, 1 H), 4.19–4.08 (m, 2 H), 3.73 (t, J = 5.2 Hz, 1
IR (KBr): 3474, 3070, 2923, 1731, 1631, 1429, 1107, 898, 743, 697,
514 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.78–7.10 (m, 22 H), 6.81 (s, 1 H),
5.42 (s, 1 H), 4.31–4.20 (m, 1 H), 4.02–3.91 (m, 1 H), 2.77–2.61 (m,
1 H), 2.45–2.32 (m, 1 H).
13C NMR (100 MHz, CDCl3): δ = 171.7, 149.5, 141.7, 141.5, 141.1,
141.0, 139.7, 135.2, 135.1, 134.2, 134.1, 133.0, 132.8, 130.8, 130.7,
130.7, 130.1, 129.8, 129.5, 129.4, 128.2, 128.1, 128.0, 127.9, 127.8,
H).
13C NMR (100 MHz, CDCl3): δ = 170.3, 149.2, 140.5, 140.4, 140.0,
139.9, 138.5, 138.3, 134.4, 133.7, 133.1, 131.5, 131.2, 129.7, 129.6,
129.1, 128.4, 128.3, 127.9, 127.0, 126.8, 126.7, 126.7, 126.5, 125.4,
125.3, 125.2, 125.0, 124.6, 120.6, 118.9, 118.8, 108.0, 74.7, 68.5,
45.2, 28.6.
HRMS (ESI): m/z [M + Na]+ calcd for C43H32O4NaSi: 663.19621;
found: 663.19589.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 1355–1361

1360
N. Li et al.
SPECIAL TOPIC
9H-Fluoren-9-yl (1S,4R)-4-Butyl-6,6-diphenyl-1,3,4,6-tetrahy-
drobenzo[c]pyrano[3,4-e][1,2]oxasiline-1-carboxylate (5f)
(minor), 6.21 min (major)]; the absolute configuration was tenta-
tively assigned by analogy.
20
Isolated as a yellow oil; yield: 36.6 mg (0.059 mmol, 59%); [α]D
–33.3 (c 0.04, CHCl3); 87% ee [HPLC (Chiracel-IC-H, hexane–
i-PrOH, 95:5, flow rate 1.0 mL/min, T = 30 °C, 254 nm): tR = 7.20
(minor), 8.55 min (major)]; the absolute configuration was tenta-
tively assigned by analogy.
IR (KBr): 3070, 3046, 2965, 2932, 1730, 1629, 1454, 1428, 1151,
1120, 875, 727, 509 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.89–7.05 (m, 22 H), 6.81 (s, 1 H),
5.46 (s, 1 H), 3.97 (dd, J = 11.2, 5.5 Hz, 1 H), 3.86 (dd, J = 11.2, 7.5
Hz, 1 H), 2.74–2.61 (m, 1 H), 1.05 (d, J = 6.9 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 171.7, 153.0, 141.7, 141.5, 141.1,
140.9, 139.8, 135.3, 135.0, 134.0, 133.0, 132.7, 130.8, 130.7, 130.6,
129.4, 129.4, 128.0, 127.9, 127.8, 127.7, 126.0, 126.0, 125.9, 125.7,
121.7, 120.0, 119.9, 107.1, 75.7, 75.1, 68.6, 33.7, 14.2.
IR (KBr): 3070, 2917, 2858, 1728, 1621, 1467, 1159, 1118, 741,
696, 510 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.81–7.00 (m, 22 H), 6.82 (s, 1 H),
5.47 (s, 1 H), 3.99–3.93 (m, 2 H), 2.53 (s, 1 H), 1.12–0.98 (m, 4 H),
0.94–0.82 (m, 2 H), 0.62 (t, J = 6.9 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 171.7, 152.4, 141.7, 141.0, 140.9,
139.9, 135.3, 135.1, 134.0, 133.0, 132.6, 130.7, 130.7, 130.5, 129.4,
129.4, 128.0, 127.8, 127.7, 127.7, 126.0, 125.8, 125.6, 121.6, 119.9,
119.9, 107.6, 75.3, 74.2, 66.9, 38.6, 29.7, 29.1, 22.8, 13.7.
HRMS (ESI): m/z [M + Na]+ calcd for C38H30O4NaSi: 601.18056;
found: 601.18014.
9H-Fluoren-9-yl (1S)-3-Methyl-6,6-diphenyl-1,3,4,6-tetrahy-
drobenzo[c]pyrano[3,4-e][1,2]oxasiline-1-carboxylate (5j)
Isolated as a yellow oil; yield: 36.4 mg (0.063 mmol, 63%); 67% ee
(major), 45% ee (minor) [HPLC (Chiracel-IA-H, hexane–i-PrOH,
90:10, flow rate 1.0 mL/min, T = 30 °C, 254 nm): tR = 5.71 (major),
6.62 min (minor); tR = 7.68 (major), 10.28 min (minor)]; the relative
configuration of 5j was determined by NOESY analysis of this
compound, the absolute configuration was tentatively assigned by
analogy.
HRMS (ESI): m/z [M + Na]+ calcd for C41H36O4NaSi: 643.22751;
found: 643.22690.
9H-Fluoren-9-yl (1S,4R)-6,6-Diphenyl-4-propyl-1,3,4,6-tetra-
hydrobenzo[c]pyrano[3,4-e][1,2]oxasiline-1-carboxylate (5g)
Isolated as a yellow solid; yield: 44.2 mg (0.073 mmol, 73%); [α]D
20
–40.8 (c 0.16, CHCl3); 88% ee [HPLC (Chiracel-IC-H, hexane–
i-PrOH, 95:5, flow rate 1.0 mL/min, T = 30 °C, 254 nm): tR = 7.39
(minor), 8.53 min (major)]; the absolute configuration was deter-
mined by X-ray crystallography analysis.
IR (KBr): 3072, 3053, 2972, 1739, 1631, 1452, 1429, 1197, 1117,
908, 745, 713, 510 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.75–6.99 (m, 22 H, major), 7.75–
6.99 (m, 22 H, minor), 6.84 (s, 1 H, minor), 6.74 (s, 1 H, major),
5.55 (s, 1 H, major), 5.43 (s, 1 H, minor), 4.17–4.05 (m, 1 H, minor),
3.96–3.85 (m, 1 H, major), 2.54–2.34 (m, 2 H, major), 2.32–2.24
(m, 2 H, minor), 1.33–1.30 (m, 3 H, major), 1.27–1.23 (m, 3 H, mi-
nor).
13C NMR (100 MHz, CDCl3): δ = 171.6, 149.9, 141.7, 141.5, 141.0,
140.8, 135.49, 135.2, 135.1, 134.9, 134.0, 130.8, 130.8, 130.7,
130.5, 129.5, 129.4, 129.3, 129.3, 128.0, 128.0, 127.9, 127.8, 127.8,
127.7, 127.7, 126.2, 125.8, 125.6, 125.6, 121.5, 120.0, 120.0, 119.8,
119.8, 107.1, 75.6, 74.5, 67.1, 37.7, 21.0.
IR (KBr): 3066, 2959, 2926, 1730, 1629, 1159, 1123, 906, 743, 504
cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.05–6.95 (m, 22 H), 6.82 (s, 1 H),
5.46 (s, 1 H), 3.96 (dd, J = 5.9, 2.3 Hz, 2 H), 2.62–2.44 (m, 1 H),
1.46–1.34 (m, 2 H), 1.20–1.12 (m, 2 H), 0.67 (t, J = 7.3 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 171.6, 152.4, 141.7, 141.5, 141.0,
140.9, 135.2, 135.0, 134.0, 130.7, 130.7, 130.5, 129.4, 129.4, 128.0,
127.8, 127.8, 127.7, 126.0, 125.8, 125.7, 121.6, 119.9, 119.9, 107.6,
75.7, 75.3, 66.9, 38.5, 31.6, 19.8, 14.1.
HRMS (ESI): m/z [M + Na]+ calcd for C40H34O4NaSi: 629.21186;
found: 629.21220.
HRMS (ESI): m/z [M + Na]+ calcd for C38H30O4NaSi: 601.18056;
found: 601.18134.
9H-Fluoren-9-yl (1S,4R)-4-Isopentyl-6,6-diphenyl-1,3,4,6-tet-
rahydrobenzo[c]pyrano[3,4-e][1,2]oxasiline-1-carboxylate (5h)
9H-Fluoren-9-yl (2S,3R)-3-[2-(Methoxydiphenylsilyl)phenyl]-
4-oxotetrahydro-2H-pyran-2-carboxylate (6)
20
Isolated as a yellow oil; yield: 41.8 mg (0.066 mmol, 66%); [α]D
–15.0 (c 0.12, CHCl3); 88% ee [HPLC (Chiracel-IC-H, hexane–
i-PrOH, 95:5, flow rate 1.0 mL/min, T = 30 °C, 254 nm): tR = 7.34
(minor), 8.37 min (major)]; the absolute configuration was tenta-
tively assigned by analogy.
Compound 5a (18 mg, 0.03 mmol) and Et3N (5 mg, 0.045 mmol)
were dissolved in MeOH (1 mL). The mixture was stirred at r.t.
overnight, and then diluted with EtOAc and washed with H2O and
brine, dried (anhyd Na2SO4), and concentrated. The residue was pu-
rified by flash column chromatography to afford 6 (14.3 mg, 0.024
mmol, 80%) as a colorless oil; [α]D20 +62.8 (c 0.23, CHCl3); 82% ee
[HPLC (Chiracel-IC-H, hexane–i-PrOH, 90:10, flow rate 1.0
mL/min, T = 30 °C, 254 nm): tR = 9.30 (major), 11.11 min (minor)];
the absolute configuration was tentatively assigned by analogy.
IR (KBr): 2956, 2920, 1732, 1622, 1451, 1265, 1119, 1016, 198,
735, 510 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.85–6.98 (m, 22 H), 6.82 (s, 1 H),
5.48 (s, 1 H), 3.95 (d, J = 5.5 Hz, 2 H), 2.65–2.22 (m, 1 H), 0.97–
0.82 (m, 5 H), 0.63 (d, J = 6.6 Hz, 3 H), 0.56 (d, J = 6.6 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 170.6, 151.3, 140.7, 140.5, 140.0,
139.9, 138.8, 134.2, 134.1, 133.0, 131.9, 131.6, 129.7, 129.6, 129.5,
128.4, 128.3, 127.0, 126.8, 126.7, 124.9, 124.8, 124.6, 120.5, 118.9,
118.8, 106.5, 74.5, 74.3, 65.0, 37.8, 34.3, 27.2, 26.3, 21.3, 21.1.
IR (KBr): 3071, 2923, 1745, 1593, 1426, 1149, 1119, 998, 945, 736,
706, 504 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.63–7.02 (m, 21 H), 6.65 (d,
J = 7.6 Hz, 1 H), 6.40 (s, 1 H), 4.20–4.03 (m, 2 H), 3.80 (t, J = 10.9
Hz, 1 H), 3.43 (d, J = 10.8 Hz, 1 H), 3.09 (s, 3 H), 2.14 (d, J = 12.7
Hz, 1 H), 2.05–1.93 (m, 1 H).
13C NMR (100 MHz, CDCl3): δ = 209.6, 170.7, 141.8, 141.5, 141.0,
141.0, 140.8, 135.8, 134.8, 134.6, 134.3, 133.6, 130.8, 130.3, 130.2,
130.0, 129.5, 129.3, 127.9, 127.7, 127.7, 127.4, 126.9, 125.9, 119.7,
119.7, 99.5, 80.5, 77.3, 65.6, 53.2, 48.6, 35.6.
HRMS (ESI): m/z [M + Na]+ calcd for C42H38O4NaSi: 657.24316;
found: 657.24276.
9H-Fluoren-9-yl (1S,4R)-4-Methyl-6,6-diphenyl-1,3,4,6-tetra-
hydrobenzo[c]pyrano[3,4-e][1,2]oxasiline-1-carboxylate (5i)
Isolated as a yellow oil; yield: 39.3 mg (0.068 mmol, 68%); [α]D
20
–20.5 (c 0.35 CHCl3); 93% ee [HPLC (Chiracel-IC-H, hexane–
i-PrOH, 90:10, flow rate 1.0 mL/min, T = 30 °C, 254 nm): tR = 5.54
HRMS (ESI): m/z [M + Na]+ calcd for C38H32O5NaSi: 619.19112;
found: 619.19025.
Synthesis 2014, 46, 1355–1361
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
Acknowledgment
Synthesis of 1,2-Oxasiline-Fused Pyrans
1361
(d) Momiyama, N.; Tabuse, H.; Terada, M. J. Am. Chem.
Soc. 2009, 131, 12882.
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D.; Toste, F. D. Chem. Rev. 2008, 108, 3351.
We are grateful for financial support from MOST (973 project
2010CB833300), NSFC (21232007 and 21172207) and the Mini-
stry of Education.
(6) (a) Mizushima, E.; Hayashi, T.; Tanaka, M. Org. Lett. 2003,
5, 3349. (b) Luo, Y.; Li, Z.; Li, C.-J. Org. Lett. 2005, 7,
2675.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnuIomprifgtooatrinSugpIoi
n
nfomartit
(7) For reviews: (a) Loh, C. C. J.; Enders, D. Chem. Eur. J.
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(11) A 73% yield of diene was isolated.
(12) Kim, S. M.; Park, J. H.; Choi, S. Y.; Chung, Y. K. Angew.
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Primary Data for this article are available online at
http://www.thieme-connect.com/ejournals/toc/synthesis and can be
cited using the following DOI: 10.4125/pd0056th. mPiDrayramPtirDayra4t0.215p/d00P56hri
m
t.yarDaZataehnl101
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© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 1355–1361