High Stereocontrol in the Preparation of Silyl-Protected γ-Substituted Enoldiazoacetates

Article abstract of DOI:10.1055/s-0037-1611865

A robust and efficient synthesis of triisopropylsilyl (TIPS)-protected γ-substituted enoldiazoacetates with excellent Z stereocontrol by using lithium bis(trimethylsilyl)azanide (LiHMDS) as a base and TIPSOTf as a silyl transfer reagent is reported. Despite their increased size compared to previously tert -butyldimethylsilyl (TBS)-protected γ-unsubstituted enoldiazoacetates, a high product yield with exceptional stereocontrol has been achieved in copper-catalyzed [3+3] cycloaddition reaction with nitrones by using a chiral indeno bisoxazoline ligand.

Full text of DOI:10.1055/s-0037-1611865

SYNLETT
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© Georg Thieme Verlag Stuttgart · New York
2019, 30, A–E
letter
A
en
K. Dong et al.
Letter
Synlett
High Stereocontrol in the Preparation of Silyl-Protected -Substi-
tuted Enoldiazoacetates
Kuiyong Donga,b
Kostiantyn O. Maricheva
Xingfang Xu*b,c
Z:E = (1–4.5):1
O
OTIPS
0
0
0
0-0
0
0
1-
7
6
7
4-9
5
0
X
R1
O
OTIPS
OR2
R1
R2O
R2O
N2
Michael P. Doyle*a
0
0
0
0-0
0
0
3-1
3
8
6-3
7
8
0
R1, R2 = alkyl
12 examples
71 89% yield
Z:E > 20:1
N2
+
TEA
TIPS OTf
a Department of Chemistry, University of Texas at San Antonio,
San Antonio, Texas 78249, United States
michael.doyle@utsa.edu
O
OTIPS
R1
b Key Laboratory of Organic Synthesis of Jiangsu Province,
College of Chemistry, Chemical Engineering and Materials
Science, Soochow University, Suzhou 215123, P. R. of China
xinfangxu@suda.edu.cn
N2
Li
O
O
O
O
R1
R1
OR2
R2O
c Guangdong Key Laboratory of Chiral Molecule and Drug Dis-
covery, School of Pharmaceutical Sciences, Sun Yat-sen Uni-
versity, Guangzhou, 510006, P. R. of China
N2
N2
LiHMDS
Received: 14.04.2019
Accepted after revision: 28.05.2019
Published online: 26.06.2019
that were formed in high yields with exclusive Z geome-
try.3,5 However, with use of triisopropylsilyl triflate (TIP-
SOTf) as the silyl transfer agent and triethylamine as the
base, product yields were high (74–93%), but stereochemi-
cal control of the product geometry was low (Table 1).
DOI: 10.1055/s-0037-1611865; Art ID: st-2019-r0210-l
Abstract A robust and efficient synthesis of triisopropylsilyl (TIPS)-
protected -substituted enoldiazoacetates with excellent Z stereocon-
trol by using lithium bis(trimethylsilyl)azanide (LiHMDS) as a base and
TIPSOTf as a silyl transfer reagent is reported. Despite their increased
size compared to previously tert-butyldimethylsilyl (TBS)-protected -
unsubstituted enoldiazoacetates, a high product yield with exceptional
stereocontrol has been achieved in copper-catalyzed [3+3] cycloaddi-
tion reaction with nitrones by using a chiral indeno bisoxazoline ligand.
Table 1 Scope of TIPS-Protected Enoldiazoacetates Obtained by Using
Triethylamine as the Basea
k
O
O
O
OTIPS
R1
TEA (1.5 equiv)
TIPSOTf (1.1 equiv)
R1
R2O
R2O
CH2Cl2, 0 °C to rt, 2–12 h
N2
N2
Key words enoldiazoacetates, Z selectivity, cycloaddition, copper ca-
talysis, nitrones, bisoxazolines
2
3
Entry
R1
R2
Me
Ratio (Z/E)b
Yield of 3 (%)c
Silyl-protected enoldiazo compounds are becoming re-
agents of choice for [3+n] cycloaddition reactions through
which their three-carbon dipolar metal carbene intermedi-
ates are able to combine with n atoms to form carbo- and
heterocyclic products in high yields and stereoselectivities.
In pursuing these transformations, 3-(tert-butyldimethylsi-
lyloxy)-2-diazo-3-butenoates (1a) were the reactants,1,2
and only two structural analogues (1b,c with R = Me and
Ph) were reported as alternatives (Figure 1).3
1
2
Et
3:1
3a, 91
3b, 84
3c, 90
3d, 74
3e, 93
3f, 85
3g, 87
3h, 90
3i, 88
3j, 82
3k, 78
3l, 85
Me
Bn
Me
3:1
3
Me
1:1
4
i-Pr
Me
1:1
5
n-C8H17
Et
Me
(2.3):1
(2.3):1
(2.2):1
2:1
6
i-Pr
7
Et
Bn
8
Et
4-BrBn
4-OMeBn
3,4,5-triOMeBn
4-CF3Bn
4-OMeBn
O
OTBS
a R1 = H; R2 = alkyl
b R1 = Me; R2 = alkyl
c R1 = Ph; R2 = alkyl
R1
9
Et
(4.5):1
2:1
R2O
10
11
12
Et
N2
Et
2:1
1
Me
(4.5):1
Figure 1 Reported enoladiazoacetates 1 used in [3+n] cycloaddition
a Reaction conditions: To 2 (2.0 mmol) in dry CH2Cl2 (10 mL) was added
Et3N (0.42 mL, 3.0 mmol) in one portion at 0 °C, followed by a dropwise
addition of TIPSOTf (0.55 mL, 2.05 mmol); and the reaction solution was
stirred at r.t. for 2–12 h.
reactions
These structural analogues were prepared by the stan-
dard procedure that converted the corresponding -keto--
diazoester to its silyl enol ether by using TBSOTf as the silyl
transfer agent and triethylamine as the base.4 This method-
ology proved to be satisfactory for the production of 1b,c
b The Z/E ratios were determined by 1H NMR analysis.
c Isolated yields of the combined Z+E isomers after flash-chromatography.
© 2019. Thieme. All rights reserved. — Synlett 2019, 30, A–E
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
K. Dong et al.
Letter
Synlett
Enoldiazoacetates with relatively small substituents at
the 4-position (Me, 3b and Et, 3a) were obtained with mod-
erate Z/E ratios of 3:1. Increasing the size of the substituent
at the 4-position (n-C8H17, 3e) diminished the ratio of Z/E to
(2.3):1 and even to 1:1 when sterically encumbered sub-
stituents (Bn, 3c or i-Pr, 3d) were introduced. To investigate
the effect of the carboxylate group on stereoselectivity, we
also prepared a series of 4-ethyl-substituted alkyl enoldia-
zoacetates 3f–3k. Isopropyl-, benzyl-, and 4-substituted
benzyl-diazoacetates in most cases (entries 6–8, 10–11) did
not show an improvement in stereoselectivity (Z/E near
2:1). Surprisingly, 4-methoxybenzyl enoldiazoacetates 3i
and 3l were obtained with a higher Z/E ratio of (4.5):1.
Desiring to produce these enoldiazoacetates as one ste-
reoisomer, we considered other methodologies used in the
production of silyl enol ethers.6 However, the diazo func-
tionality places limitations on acceptable methodologies,
especially the need to avoid acids. Simple alternative strate-
gies, such as use of lower temperatures or different leaving
groups and bases did not offer advantages. Our investiga-
tion was carried out with -keto--diazoester 2a and triiso-
propylsilyl trifluoromethanesulfonate as model substrates
in dichloromethane (CH2Cl2) at 0 °C (Table 2). As part of our
previous work on enoldiazoacetates, triethylamine (Et3N)
was used as the base, and the desired product 3a was
formed in excellent yield (91%) but with low stereoselectiv-
ity (entry 1, Z/E = 3:1). Several amine bases were screened
in this transformation (entries 2–7), but none of them gave
any advantage in terms of both the yield and selectivity.
Most of the starting material (2a) was recovered because of
the competing facile TIPS transfer to the nitrogen atom of
those bases (entries 2–4, 6–7). Attempted optimization by
changing the concentration of Et3N did not show an im-
provement (ratios Z/E were lower at either lower or higher
concentration, entries 8, 9). The use of other solvents either
lowered the Z/E ratio (entry 10) or the yield of 3a (entries
11, 12). Temperature screening provided a higher ratio of
Z/E when the reaction was carried out at –78 °C by using
N,N-diisopropylethylamine (DIPEA) as the base (entry 14,
Z/E = 6:1). All of the results obtained with the use of amines
are consistent with initial silicon attachment to the ketone-
carbonyl group of the diazoacetoacetate followed by proton
transfer enolization of the silyl-activated -diazo--ketoac-
etate (Lewis acid-initiated enolization).7 The TIPS group is
sufficiently large to change the conformational preference
of torms the Z isomer.he silyl-activated -diazo--keto-
acetate (Figure 2) inhibiting product formation from the
conformation that preferentially forms the Z isomer.
As a consequence of these results, we considered em-
ploying the enolate alternative: the use of a strong base
with a lithium cation that activates the ketone through pre-
sumed bidentate lithium ion coordination with both car-
bonyl oxygens of the ketoester that enforces proton abstrac-
tion by the base on the conformation that favors formation
of the Z lithium enolate. Subsequent nucleophilic attack of
TIPS-OTf by the enolate would produce the desired silyl
enoldiazoacetate with high stereocontrol.8 A strong base,
lithium diisopropylamide (LDA), was initially used in the
model reaction (Table 2, entry 15), and enoldiazoacetate 3a
was formed in good yield (74%) but with only a modest Z/E
ratio of (5.5):1. In contrast, the more sterically encumbered
lithium salt, lithium bis(trimethylsilyl)azanide (LiHMDS),
showed a much better result to afford 3a in 88% yield with
Table 2 Synthesis of TIPS-Protected Enoldiazoacetate 3a: Reaction
Optimizationa
k
O
O
O
OTIPS
Et
base (1.2 equiv)
TIPSOTf (1.1 equiv)
MeO
MeO
solvent, 0 °C
N2
N2
3a
2a
Entry
Base
Solvent
Ratio (Z/E)b
Yield of 3a (%)c
1
2
Et3N
DIPEA
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
chloroform
toluene
THF
3:1
91
51
37
21
82
15
23
88
89
82
20
41
91
71
74
88
n.d.
4:1
3d
i-Pr2NH
pyridine
DABCO
pyrrolidine
piperidine
Et3N
(1.3):1
(1.5):1
1:1
4d
5
6d
1:(1.8)
1:(1.5)
(2.8):1
(1.1):1
(1.8):1
(2.4):1
(2.3):1
(2.4):1
6:1
7d
8e
9f
Et3N
10
11d
12
13g
14g
15g
16g
17g,h
Et3N
Et3N
Et3N
Et3N
CH2Cl2
CH2Cl2
THF
DIPEA
LDA
(5.5):1
>20:1
–
LiHMDS
LiHMDS
THF
THF
a Reaction conditions: To 1a (85 mg, 0.50 mmol) and base (0.60 mmol) in
solvent (2.0 mL) was added TIPSOTf (169 mg, 0.55 mmol) under an argon
atmosphere at 0 °C.
TIPS
TIPS
R1
O
O
O
O
OR2
OR2
b Z/E ratios were determined by 1H NMR analysis,
c Isolated yields after flash-chromatography.
R1
N2
favored
N2
less favored
d Most of material 2a was recovered.
e The reaction was carried out at the conc. of 0.1 M.
f The reaction was carried out at the conc. of 0.5 M.
g The reaction was carried at –78 °C.
Figure 2 Preferential formation of E isomer in Lewis acid-initiated eno-
lization of -keto--diazoesters
h TIPSCl was used; n.d. = no product was detected.
© 2019. Thieme. All rights reserved. — Synlett 2019, 30, A–E

C
K. Dong et al.
Letter
Synlett
an Z/E ratio of >20:1 (entry 16). In addition to the remark-
able level of Z selectivity of the enolization, this procedure
also gives complete reaction in just five minutes. The use of
chloride instead of triflate as the leaving group in the silyl
transfer agent did not lead to the desired product 3a (entry
17); only starting material 2a was recovered.
3 in high yields (76–89%) with excellent Z stereoselectivity
(Z/E >20:1).
Our ultimate goal is to use the obtained -substituted
enoldiazoacetates 3 as the reactants in [3+n] cycloaddition
reactions. Therefore, to demonstrate the practicality and
synthetic utility of the current method, 5 mmol scale reac-
tions were carried out (Scheme 1). On this scale the desired
-substituted enoldiazoacetates 3 were obtained in compa-
rable high yields and excellent stereocontrol.
Having the optimized conditions in hand, we converted
a variety of substrates 2 to the corresponding enoldiazoace-
tates 3 effectively with exclusive Z stereoselectivity (Z/E >
20:1) (Table 3). -Keto--diazoesters 2 with small substi-
tuents R1 = Et, Me underwent a smooth conversion to
enoldiazoacetates 3a,b in good yields (71–88%) (entries 1,
2). More sterically hindered alkyl groups such as Bn (2c)
and i-Pr (2d) also worked well and afforded the desired
products 3c,d in high yields (85–87%). The long chain n-oc-
tyl group (2e) was also tolerated in this process to produce
enoldiazoacetate 3e in high yield (81%). Furthermore, we
explored the substituent variations in the ester group, and
the nature of the substituents at the 4-position (R1) of -
keto--diazoester 2 (Me or Et) did not affect the reaction
outcome. The isopropyl ester (2f) and a series of benzyl -
keto--diazoesters 2 bearing electron-neutral (2g), -donat-
ing (2h–1j and 2l), or -withdrawing (2k) substituents on
the aromatic ring smoothly underwent the enolization
with TIPSOTf to afford the corresponding enoldiazoacetates
LiHMDS (1.2 equiv)
TIPSOTf (1.1 equiv)
O
OTIPS
R1
O
O
R1
R2O
R2O
THF, –78 °C, 5–10 min
N2
N2
3
2
(5 mmol)
2a, R1 = Et, R2 = Me
2e, R1 = C8H17, R2 = Me
2i, R1 = Et, R2 = PMB
3a, R1 = Et, R2 = Me, 1.42 g, 87% yield, Z/E > 20:1
3e, R1 = C8H17, R2 = Me, 1.77 g, 86 yield, Z/E > 20:1
3i, R1 = Et, R2 = PMB,1.80 g, 83% yield, Z/E > 20:1
Scheme 1 Examples of the 5 mmol scale syntheses of -substituted
enoldiazoacetates with high Z stereocontrol
In a previous study of the enantioselective [3+3] cyclo-
addition of TBS-protected (Z)-4-phenyl-substituted enoldi-
azoacetates, we reported that dirhodium catalysts were un-
able to effect [3+3] cycloaddition with nitrones but that sil-
ver/t-BuBOX [BOX: bis(oxazoline)] catalysis was effective.3d
There is no other example of a [3+3] cycloaddition reaction
of a -substituted enoldiazoacetate with a nitrone, and we
anticipated that there could be a significant barrier to cyc-
loaddition with the bulkier TIPS-protected -substituted
enoldiazoacetates. However, we have found that the repre-
sentative substrate, TIPS-protected (Z)-4-octyl-substituted
enoldiazoacetate 3e, undergoes cycloaddition with nitrone
4 using copper(I)/InBOX catalysis (Scheme 2). Chiral ox-
azine 5 was obtained as a single diastereomer in high yield
(93%) and enantioselectivity (93% ee), and its absolute con-
figuration was determined by comparison of the sign of op-
tical rotation with those of previously reported [3+3] cyc-
loaddition products to be (3S,6R).3d Notably, the same
transformation under silver/t-BuBOX catalysis resulted in a
high yield (81%) of oxazine 5 but negligible enantioselectiv-
ity (Scheme 2), which indicates the substantial effect of li-
gand and metal catalyst to stereocontrol of this process. In
addition, two other combinations of metal–ligand
[Cu(MeCN)4PF6/(S)-t-BuBOX and AgSbF6/L1] did not provide
an improvement in enantioselectivity (30 and 38% ee, re-
spectively, Scheme 2), although the yields of oxazine 5 were
high (83–88%). As anticipated, other examples of -substi-
tuted enoldiazoacetates 3 also gave high yields and selectiv-
ities in [3+3] cycloaddition with nitrone 4 with use of the
Cu(I)/L1 catalyst.
Table 3 Scope of TIPS-Protected Enoldiazoacetates Obtained by Using
LiHMDS as the Base9,a
k
O
O
LiHMDS (1.2 equiv)
TIPSOTf (1.1 equiv)
O
OTIPS
R1
R1
R2O
R2O
THF, –78 °C, 5–10 min
N2
N2
2
3
Entry
R1
R2
Me
Ratio (Z/E)b
Yield of 3 (%)c
1
2
Et
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
3a, 88
3b, 71
3c, 85
3d, 87
3e, 81
3f, 88
3g, 81
3h, 83
3i, 82
3j, 77
3k, 89
3l, 76
Me
Bn
Me
3
Me
4
i-Pr
Me
5
n-C8H17
Et
Me
6
i-Pr
7
Et
Bn
8
Et
4-BrBn
4-OMeBn
3,4,5-triOMeBn
4-CF3Bn
4-OMeBn
9
Et
10
11
12
Et
Et
Me
a Reaction conditions: to 1 (0.50 mmol) in THF (2.0 mL) LiHMDS (0.60 mL,
0.60 mmol, 1.0 M in hexane) followed by TIPSOTf (169 mg, 0.55 mmol)
were added dropwise under N2 atmosphere at –78 °C.
b Z/E ratios were determined by 1H NMR analysis.
A motivation for the use of the TIPS-protected -substi-
tuted enoldiazoacetates is our discovery that [3+1] cycload-
dition of enoldiazoesters3a did not occur with TBS-protect-
c Isolated yields after flash chromatography.
© 2019. Thieme. All rights reserved. — Synlett 2019, 30, A–E

D
K. Dong et al.
Letter
Synlett
In summary, we have demonstrated the robust synthe-
sis of TIPS-protected -substituted enoldiazoacetates with
excellent Z stereoselectivity. Products were obtained in high
yields from common -keto--diazoesters by using LiHMDS
as a base and TIPSOTf as a silyl transfer reagent. Besides
high stereocontrol, another great advantage of this method
is the possibility to prepare -substituted enoldiazoacetates
in just five minutes. In addition, the first example of highly
enantioselective copper-catalyzed [3+3] cycloaddition of si-
lyl-protected (Z)-4-alkyl-substituted enoldiazoacetate with
nitrone is reported. Future studies that focus on the appli-
cation of solely the Z stereoisomer of enoldiazoacetates in
[3+n] cycloaddition reactions with stable dipoles are under-
way in our laboratory.
Scheme 2 An example of a highly enantioselective copper(I)-catalyzed
[3+3] cycloaddition of silyl-protected -substituted enoldiazoacetate 3e
with nitrone 4
ed -substituted enoldiazoacetates. To exemplify the pro-
cess, treatment of TIPS-protected (Z)-4-ethyl-substituted
enoldiazoacetate 3a with sulfur ylide 6 by using a cop-
per(I)/SaBOX catalyst (Scheme 3) gave chiral cyclobutene 7
in high yield (74%) and enantioselectivity (90% ee) as a sin-
gle diastereomer.
Funding Information
We acknowledge the U.S. National Science Foundation (CHE-
1763168) for funding this research. The NMR spectrometer used in
this research was supported by a grant from the U.S. National Science
Foundation (CHE-1625963). K.D. acknowledges the support from
China Scholarship Council (CSC).
D
i
v
i
si
o
n
of
C
h
e
m
i
stry(C
H
E-1
6
2
5
9
6
3)D
i
v
i
si
o
n
of
C
h
e
m
i
stry(C
H
E-1
7
6
3
1
6
8)
Another example of the utility of this methodology is
found in reactions with 1-methylindole 8. In contrast to pri-
or reports of [3+2] cycloaddition with enoldiazoacetates,10
the TIPS-protected -substituted enoldiazoacetate 3a (Z/E >
20:1) gave the product from formal C–H functionalization
(9) exclusively (88% isolated yield) in reactions catalyzed by
rhodium acetate (Scheme 4). In contrast, the same reaction
over the same reaction time with 3a (Z/E = 1:1) gave a low
yield of 9 and produced the donor–acceptor cyclopropene
10 in only 51% combined yield.
Acknowledgment
We thank W. G. Griffith (UTSA) for mass spectral analyses.
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1611865.
S
u
p
p
orit
n
gInformati
o
n
S
u
p
p
orit
n
gInformati
o
n
O
OTIPS
Et
TIPSO
Et
CO2Me
CuOTf Tol1/2 (5.0 mol%)
O
Me
S
L2 (6.0 mol%)
+
MeO
Ph
O
Ph
Me
CH2Cl2, r.t., 24 h
N2
3a, Z/E > 20:1
t-Bu
t-Bu
6
7
74%, >20:1 dr, 90% ee
O
O
N
N
Ph
Ph
L2
Scheme 3 An example of copper(I)-catalyzed [3+1] cycloaddition of silyl-protected -substituted enoldiazoacetate 3a with sulfur ylide 6
OTIPS
MeO2C
O
OTIPS
Et
Et
Rh2(OAc)4 (1.0 mol%)
CHCl3, r.t., 4 h
+
MeO
N
N2
3a, Z/E > 20:1
N
Me
Me
8
9
88% yield
CO2Me
OTIPS
O
OTIPS
Et
Rh2(OAc)4 (1.0 mol%)
CHCl3, r.t., 4 h
9
+
+
Et
MeO
34% yield
N
N2
3a, Z/E = 1:1
Me
10
8
17% yield
Scheme 4 An example of rhodium(II)-catalyzed reaction of silyl-protected -substituted enoldiazoacetate 3a with 1-methylindole 8
© 2019. Thieme. All rights reserved. — Synlett 2019, 30, A–E

E
K. Dong et al.
Letter
Synlett
References and Notes
(8) (a) Ireland, R. E.; Mueller, R. H.; Willard, A. K. J. Am. Chem. Soc.
1976, 98, 2868. (b) Fataftah, Z. A.; Kopka, I. E.; Rathke, M. W.
J. Am. Chem. Soc. 1980, 102, 3959. (c) Corey, E. J.; Gross, A. W.
Tetrahedron Lett. 1984, 25, 495.
(1) For reviews, see: (a) Xu, X.; Doyle, M. P. Acc. Chem. Res. 2014, 47,
1396. (b) Deng, Y.; Cheng, Q.-Q.; Doyle, M. P. Synlett 2017, 28,
1695. (c) Cheng, Q.-Q.; Deng, Y.; Lankelma, M.; Doyle, M. P.
Chem. Soc. Rev. 2017, 46, 5425. (d) Yin, Z.; He, Y.; Chiu, P. Chem.
Soc. Rev. 2018, 47, 8881. (e) Marichev, K. O.; Doyle, M. P. Org.
Biomol. Chem. 2019, 17, 4183.
(2) For recent research articles, see: (a) Li, S.-J.; Fang, D.-C. Organo-
metallics 2018, 37, 1373. (b) Marichev, K. O.; Adly, F. G.;
Carranco, A. M.; Garcia, E. C.; Arman, H.; Doyle, M. P. ACS Catal.
2018, 8, 10392.
(3) (a) Deng, Y.; Massey, L. A.; Zavalij, P.; Doyle, M. P. Angew. Chem.
Int. Ed. 2017, 56, 7479. (b) Deng, Y.; Massey, L. A.; Rodriguez
Núñez, Y. A.; Arman, H.; Doyle, M. P. Angew. Chem. Int. Ed. 2017,
56, 12292. (c) Xu, X.; Zavalij, P. Y.; Hu, W.; Doyle, M. P. J. Org.
Chem. 2013, 78, 1583. (d) Xu, X.; Zavalij, P. J.; Doyle, M. P. Chem.
Commun. 2013, 49, 10287. (e) Qian, Y.; Xu, X.; Wang, X.; Zavalij,
P. J.; Hu, W.; Doyle, M. P. Angew. Chem. Int. Ed. 2012, 51, 5900.
(f) Xu, X.; Zavalij, P. J.; Doyle, M. P. Angew. Chem. Int. Ed. 2012,
51, 9829.
(4) (a) Shved, A. S.; Tabolin, A. A.; Novikov, R. A.; Nelyubina, Y. V.;
Timofeev, V. P.; Ioffe, S. L. Eur. J. Org. Chem. 2016, 5569. (b) Zhu,
C.; Xu, G. Sun J. 2016, 55, 11867. (c) Nocquet, P.-A.; Opatz, T. Eur.
J. Org. Chem. 2016, 1156. (d) Xu, X.; Wang, X.; Zavalij, P. Y.;
Doyle, M. P. Org. Lett. 2015, 17, 790.
(9) General Procedure for the Preparation of (Z)-Enoldiazoace-
tates 3: A 10 mL oven-dried vial equipped with a magnetic stir-
ring bar was charged with diazoacetate 2 (0.50 mmol) and the
system was filled with nitrogen. THF (2.0 mL) was then added,
and the reaction solution was cooled to –78 °C (dry ice/acetone
bath). LiHMDS (0.60 mL, 1.0 M in the hexanes) was introduced
dropwise in 2 min, followed by the addition of TIPSOTf (168.5
mg, 0.55 mmol) at –78 °C. The resulting solution was stirred at
–78 °C until the reaction was complete (monitored by TLC,
about 5–15 min). THF was then removed under reduced pres-
sure, and the residue was purified by column chromatography
on silica gel which was pretreated with triethylamine
(5 vol.%)/hexanes (eluent: pure hexanes) to give the desired
products 3 in high yields and excellent stereoselectivity.
Methyl
(Z)-2-Diazo-3-[(triisopropylsilyl)oxy]hex-3-enoate
(3a): Orange oil; Yield: 138 mg (88%). 1H NMR (500 MHz,
CDCl3):  = 5.07 (t, J = 7.2 Hz, 1 H), 3.80 (s, 3 H), 2.15–2.22
(comp, 2 H), 1.24–1.16 (comp, 3 H), 1.12 (d, J = 6.6 Hz, 18 H),
1.01 (t, J = 7.4 Hz, 3 H), 13C NMR (125 MHz, CDCl3):  = 165.8,
133.4, 116.3, 52.1, 19.7, 18.0, 14.1, 13.5; HRMS (ESI): m/z [M + H]+
calcd for C16H31N2O3Si: 327.2098; found: 327.2093.
Methyl (Z)-2-Diazo-3-[(triisopropylsilyl)oxy]pent-3-enoate
(3b): Orange oil; Yield: 111 mg (71%). 1H NMR (500 MHz,
CDCl3):  = 5.13 (q, J = 7.0 Hz, 1 H), 3.77 (s, 3 H), 1.70 (d, J = 7.0
Hz, 3 H), 1.20–1.13 (comp, 3 H), 1.10 (d, J = 6.7 Hz, 18 H); 13C
NMR (125 MHz, CDCl3):  = 165.8, 134.7, 108.7, 52.1, 18.0, 13.5,
(5) (a) Wang, X.; Zhou, Y.; Qiu, L.; Yao, R.; Zheng, Y.; Zhang, C.; Bao,
X.; Xu, X. Adv. Synth. Catal. 2016, 358, 1571. (b) Deng, Y.; Jing, C.;
Doyle, M. P. Chem. Commun. 2015, 51, 12924.
(6) (a) Fleming, I. Organic silicon chemistry., In: Comprehensive
organic chemistry, Vol. 3; Barton, D. H. R.; Ollis, W. D., Ed.; Per-
gamon: Oxford, 1979, 541. (b) Brownbridge, P. Synthesis 1983,
1. (c) Weber, W. P. Preparation of Silyl Enol Ethers, In: Silicon
Reagents for Organic Synthesis. Reactivity and Structure Concepts
in Organic Chemistry, Vol. 14; Springer: Berlin/Heidelberg, 1983.
(d) Fleming, I. A primer in organmilicon biochemistry, In: Silicon
Biochemistry (Ciba Foundation Symposium No. 121); Wiley: New
York, 1986, 112. (e) Walshe, N. D. A.; Goodwin, G. B. T.; Smith, G.
C.; Woodward, F. E. Org. Synth. 1987, 65, 1.
11.9; HRMS (ESI): m/z [M
+
H]+ calcd for C15H29N2O3Si:
313.1942; found: 313.1935.
Methyl (Z)-2-Diazo-5-phenyl-3-[(triisopropylsilyl)oxy]pent-
3-enoate (3c): Orange oil, Yield 165 mg (85%). 1H NMR (500
MHz, CDCl3):  = 7.29 (t, J = 7.5 Hz, 2 H), 7.23 (d, J = 7.1 Hz, 2 H),
7.19 (t, J = 7.2 Hz, 1 H), 5.31 (t, J = 7.4 Hz, 1 H), 3.78 (s, 3 H), 3.54
(d, J = 7.4 Hz, 2 H), 1.26–1.18 (comp, 3 H), 1.13 (d, J = 6.9 Hz, 18
H); 13C NMR (125 MHz, CDCl3)  = 165.6, 141.0, 134.6, 128.5,
128.5, 126.1, 112.6, 52.1, 32.5, 18.0, 13.5; HRMS (ESI): m/z [M + H]+
calcd for C21H33N2O3Si: 389.2255; found: 389.2251.
(7) Lienhard, G. E.; Wang, T.-C. J. Am. Chem. Soc. 1969, 91, 1146.
For more examples, see the Supporting Information.
(10) Jing, C.; Cheng, Q.-Q.; Deng, Y.; Arman, H.; Doyle, M. P. Org. Lett.
2016, 18, 4550.
© 2019. Thieme. All rights reserved. — Synlett 2019, 30, A–E