Ether-directed diastereoselectivity in catalysed Overman rearrangement: comparative studies of metal catalysts

Article abstract of DOI:10.1016/j.tet.2008.03.099

Ether-directed diastereoselectivity in Overman rearrangement of δ-methoxy and δ-TBDMSO substituted allylic trichloroacetimidates has been explored using PtCl₂, PtCl₄, AuCl and AuCl₃ catalysts in comparison with commonly us

Full text of DOI:10.1016/j.tet.2008.03.099

Tetrahedron 64 (2008) 5794–5799
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Ether-directed diastereoselectivity in catalysed Overman
rearrangement: comparative studies of metal catalysts
,
,b,
Ieva Jaunzeme a b, Aigars Jirgensons a
*
a Faculty of Material Science and Applied Chemistry, Riga Technical University, Riga, LV 1048, Latvia
b Latvian Institute of Organic Synthesis, Riga, LV 1006, Latvia
a r t i c l e i n f o
a b s t r a c t
Article history:
Ether-directed diastereoselectivity in Overman rearrangement of d-methoxy and d-TBDMSO substituted
allylic trichloroacetimidates has been explored using PtCl2, PtCl4, AuCl and AuCl3 catalysts in comparison
with commonly used Pd(II) catalysts. For both substrates the use of PtCl2 catalyst gave notably improved
anti/syn-ratio of 1,2-aminoalcohol derivatives (anti/syn¼11:1 for d-methoxy; 6:1 for d-TBDMSO) com-
pared to all metal catalysts known to promote Overman rearrangement. Formation of 2-tri-
chloromethyloxazoline was observed as a dominant side reaction in the metal catalysed rearrangement
of d-methoxy substituted allylic trichloroacetimidates considerably reducing the yield of the desired
product. This side reaction was suppressed when d-TBDMS-ether was used as a directing group.
Ó 2008 Elsevier Ltd. All rights reserved.
Received 12 December 2007
Received in revised form 9 March 2008
Accepted 27 March 2008
Available online 3 April 2008
1. Introduction
were used as substrates (anti/syn¼4:1, 5:1 and 7:1, respectively). MOM
group substitution at the d-oxygen provided a very strong directing
The rearrangement of O-allyltrichloroacetimidates to N-allyl-
trichloroacetamides, first discovered by Overman, is a useful
approach for the synthesis of nitrogen containing compounds.1 The
rearrangement can be performed thermally at elevated tempera-
tures or catalysed by ‘soft’ metal salts at very mild reaction condi-
tions. Recently developed chiral cobalt oxazoline palladacycle
(COP-Cl) catalysts provide a possibility to achieve enantioselective
rearrangement of prochiral O-allyltrichloroacetimidates.2 Substrate
controlled stereochemical induction has been intensively studied
for catalytic rearrangement of O-allyltrichloroacetimidates bearing
a metal chelating group adjacent to the double bond.3,4 High dia-
stereoselectivity has been reported in Pd(II) catalysed rearrange-
ment of trichloroacetimidates with d-tert-butoxycarbonylamino
group giving access to orthogonally protected anti-1,2-diamines.3
Recent investigations by Jamieson and Sutherland as well as others
have been devoted to the d-ether directed 1,2-stereoinduction in
the Pd(II) catalysed rearrangement of trichloroacetimidates leading
preferentially to anti-1,2-aminoalcohol derivatives (Fig. 1).4 It has
been shown that anti/syn-selectivity in rearrangement of allylic
trichloroacetimidates is largely influenced by the d-oxygen
substituent R1. Rearrangement proceeds with low stereoselectivity
when the oxygen substituent R1 is a bulky TBDMS group (anti/
syn¼2:1).4a Medium anti-stereoselectivity was observed when d-hy-
droxy, d-methoxy or d-ethoxy substituted O-allyltrichloroacetimidates
effect to give anti-1,2-aminoalcohol derivatives in high diastereomeric
excess (anti/syn¼10–15:1, depending on the solvent).4a,c
In the proposed stereoinduction model, palladium coordinates
with both the oxygen atom and the double bond, selecting the
diastereotopic face of the double bond that leads to the complex
with minimised 1,3-allylic strain (Fig. 1).4d The addition of tri-
chloroacetimidate occurs from the uncomplexed face of the acti-
vated alkene according to a cyclisation induced rearrangement
(CIR) mechanism.1d
Recently, we have reported Pt(II), Pt(IV), Au(I) and Au(III) as new
catalysts for the Overman rearrangement.5 In this publication, we
present our investigation of these metals as catalysts for the
ether-directed diastereoselective rearrangement in comparison
with commonly used Pd(II) catalysts. d-Methoxy and d-TBDMSO
substituted allylic trichloroacetimidates were chosen as test
substrates since diastereoselectivity in the rearrangement of such
substrates requires substantial improvement. The use of the TBDMS
etheras a directing group is of notable synthetic importance since O-
TBDMS-protected 1,2-aminoalcohol derivatives obtained as rear-
rangement products have high potential for further derivatisation.
R1
R
R1
R
H
O
O
R1
[M]
O
O
R
HN
HN
O
HN
O
CCl3
CCl3
CCl3
* Corresponding author. Tel.: þ371 29 33 4948; fax: þ371 754 14 08.
E-mail address: aigars@osi.lv (A. Jirgensons).
Figure 1. Proposed stereoinduction model.4d
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.03.099

I. Jaunzeme, A. Jirgensons / Tetrahedron 64 (2008) 5794–5799
5795
R1
R1
R1
iii (R1= TBDMS)
iv (R1= Me)
i (R1= TBDMS)
ii (R1= Me)
OH
O
O
O
v
O
O
O
R
R
R
R
OAlk1
OAlk
OH
OAlk
5-9
1-4
10-14
5-19
Scheme 1. Reagents and conditions: (i) TBDMSCl (1.1 equiv), imidazole (1.2 equiv), CH2Cl2; (ii) NaH (1.2 equiv), MeI (1.2 equiv), THF, 0 ꢀC; (iii) (a) DIBAL-H (1.1 equiv), Et2O, ꢁ78 ꢀC,
(b) (EtO)2P(O)CH2CO2Et (1.1 equiv), NaH (1.2 equiv), Et2O or Ph3PCHCO2Me (1.1 equiv), toluene, reflux; (iv) (a) LiAlH4 (1.0 equiv), Et2O, 0 ꢀC, (b) DMSO (2.4 equiv), (COCl)2 (1.2 equiv),
NEt3 (5.0 equiv), CH2Cl2, (c) (EtO)2P(O)CH2CO2Et (4.2 equiv), NaH (4.2 equiv), Et2O; (v) DIBAL-H (2.2 equiv), Et2O, ꢁ78 ꢀC to rt.
2. Results and discussion
OH
O
Me
The key intermediates for the synthesis of O-allyltri-
chloroacetimidatesdallylic alcohols 15–19, were prepared
according to a slightly modified known synthetic route (Scheme
1).4a Commercially available a-hydroxy-carboxylic acid esters 1–4
were O-derivatised with MeI or TBDMSCl. The resulting methyl
ether 5 was transformed to a,b-unsaturated ester 10 using a three-
step procedure that involves reduction of the ester to the primary
alcohol, Swern oxidation and Horner–Wadsworth–Emons olefina-
tion.4a Unfortunately, we were not able to achieve the yield of the
ester 10 reported in the literature probably due to high volatility of
intermediates. Final reduction of a,b-unsaturated ester 10 using
standard procedure with DIBAL-H resulted in allylic alcohol 15 in
low overall yield. TBDMS-protected esters 6–9 were reduced to
aldehydes and these were used without further purification in the
olefination reaction to yield a,b-unsaturated esters 11–14. After
separation of the undesired Z-isomer in the case of olefins 12–14, all
esters 11–14 were reduced using DIBAL-H to allylic alcohols 16–19
in good overall yields (Table 1).
N
H
CCl3
25
Figure 2. The product 25 of oxazoline 24 ring opening.
cases product 24 was isolated in trace amounts after flash
chromatography.
The best anti/syn-ratio of the amide 22 was achieved using PtCl2
as catalyst (Table 2, entry 1), which was higher than using Pd(II)
catalysts (entries 5 and 6). Moreover, compared to all other metal
catalysts explored, PtCl2 catalysed reaction was the least favourable
for undesired oxazoline 24 formation and consequently amide 22
was obtained in improved yield. In the case of AuCl and AuCl3, the
lowest anti-22/syn-22 ratio and the highest formation of oxazoline
24 was obtained (entries 3 and 4).
Similar results were observed with d-TBDMSO substituted
trichloroacetimidate 21 as the rearrangement substrate (Table 3).
High yield of rearrangement product 23 and substantially improved
Trichloroacetimidates 20 and 21 were freshly prepared from
allylic alcohols 15 and 16 by a standard procedure and subjected to
catalysis using PtCl2, PtCl4, AuCl, AuCl3 as well as PdCl2 as the
reference catalyst in CH2Cl2 (Scheme 2). The reaction was run for
18 hdthis was a sufficient time to achieve complete conversion of
trichloroacetimidates 20 and 21 (according to TLC or GC). After
removal of the catalyst by filtration trough a pad of FlorisilÒ, reaction
mixture was studied by GC analysis and 1H NMR spectroscopy.
According to 1H NMR spectroscopic data of the crude reaction
mixture obtained from the rearrangement of d-methoxy
substituted trichloroacetimidate 20, the expected Overman rear-
rangement products anti-22 and syn-22 were formed together with
oxazoline 24 as the main side product. Isolation of oxazoline 24
proved to be difficult due to its volatility and low stability when
exposed to moisture in the presence of the Lewis acidic catalyst. As
a result, trichloroacetamide 25 (Fig. 2) was obtained when the
product mixture was separated by flash chromatography. In several
Table 2
Rearrangement of d-methoxytrichloroacetimidate 20
Entry
Catalyst
Yield of
22 (%)
Ratiob
(anti/syn)
Ratioc
of 22:24
Yield of
25 (%)
1.
2.
3.
4
5.
6.
PtCl2
PtCl4
AuCl
AuCl3
PdCl2
PdCl2(MeCN)2
65
35
48
41
50
49a
11:1
10:1
5:1
3:1
2:1
1:1
1:1
2:1
d
16
12
d
d
21
d
5:1
8:1
7:1a
a
a
Data from Ref. 4a.
According to GC analysis of crude reaction mixture.
According to 1H NMR spectroscopic data of crude reaction mixture.
b
c
Table 3
Rearrangement of d-TBDMSO-trichloroacetimidate 21
Entry
Catalyst
Yield of
Ratiob
Ratioc
Yield of
23 (%)
(anti/syn)
23: 24
25 (%)
Table 1
1.
2.
3.
4.
5.
6.
PtCl2
PtCl4
AuCl
AuCl3
PdCl2
PdCl2(MeCN)2
85
50
70
40
62
68a
6:1
6:1
2:1
2:1
2:1
2:1a
8:1
10:1
5:1
5:1
n.d.
d
8
Substitution pattern, configuration and overall yield of allylic alcohols 15–19
d
d
d
d
d
Compound
Configuration
Alk
Alk1
R
R1
Overall yield (%)
1, 5, 10, 15
1, 6, 11, 16
2, 7, 12, 17
3, 8, 13, 18
4, 9, 14, 19
S
S
S,R
S,R
S
Me
Me
Et
Me
Me
Et
Et
Me
Me
Me
Me
Me
Bu
Ph
i-Pr
Me
8
52
52
52
59
a
TBDMS
TBDMS
TBDMS
TBDMS
a
Data from Ref. 4a.
According to GC analysis of crude reaction mixture.
According to 1H NMR spectroscopic data of crude reaction mixture.
b
c
OR1
HN
OR1
HN
OR1
HN
Me
i
ii
Me
Me
Me
+
+
15-16
N
O
O
O
O
CCl3
CCl3
anti-22 R1 = Me
CCl3
CCl3
20 R1 = Me (93%)
syn-22 R1 = Me
24
21 R1 = TBDMS (99%) anti-23 R1 = TBDMS syn-23 R1 = TBDMS
Scheme 2. Reagents and conditions: (i) CCl3CN (1.1 equiv), NaH (10 mol %), Et2O, 0 ꢀC to rt; (ii) catalyst, CH2Cl2, rt.

5796
I. Jaunzeme, A. Jirgensons / Tetrahedron 64 (2008) 5794–5799
OTBDMS OTBDMS OTBDMS
Ph
i
R
ii
R
R
17-19
+
+
N
O
HN
O
O
O
HN
HN
CCl3
CCl3
anti-29-31
CCl3
syn-29-31
CCl3
26-28
32
Scheme 3. Reagents and conditions: (i) CCl3CN (1.1 equiv), NaH (10 mol %), Et2O, 0 ꢀC to rt; (ii) catalyst, CH2Cl2, rt.
anti-23/syn-23 ratio was obtained with PtCl2 as the catalyst (entry
1). Again AuCl and AuCl3 gave the lowest anti-23/syn-23 ratio and
highest formation of oxazoline 24 (entries 3 and 4). Noteworthy, in
all cases oxazoline 24 formation was less favourable from
d-TBDMSO substituted trichloroacetimidate 21 compared to
d-methoxy substituted trichloroacetimidate 20.
Me
Me
Me
Me
[M]
Me
Me
O
[M]
O
O
HN+
O
[M]
HN+
O
HN
O
?
CCl3
CCl3
20*[M]
CCl3
34
33
Structurally different d-TBDMSO substituted O-allylic tri-
chloroacetimidates 26–28 were used as substrates for the PtCl2 and
PdCl2 catalysed Overman rearrangement (Scheme 3). Good yields
with both catalysts were observed only in the case of n-Bu
substituted trichloroacetimidate 26 (Table 4, entries 1 and 2). PtCl2
again provided considerably better anti/syn-ratio compared to
PdCl2 catalyst. Trichloroacetimidate 27 bearing phenyl substituent
gave low chemical yield and anti/syn-selectivity of amides anti,syn-
30 (Table 3, entries 3 and 4) and notable amount of oxazoline 32.
Oxazoline 32 was stable to be isolated by flash chromatography in
52% for PtCl2 and 44% yield for PdCl2 catalysed reactions. In the case
of trichloroacetimidate 28 bearing an iso-propyl substituent,
decomposition was observed with only trace of amide 31 formation
(Table 3, entries 5 and 6) leading to the mixture of unidentified
products. In this case, formation of oxazoline was not observed in
contrast to other rearrangement substrates 20, 21 and 26, 27.
The formation of oxazolines 24 and 32 in the rearrangement of
trichloroacetimidates 20, 21 and 27 deserves attention as a domi-
nant side reaction in the rearrangement of d-oxy substituted allylic
trichloroacetimidates.
-[M]
-MeOH
-[M]
Me
Me
Me
O
N
O
O
HN
CCl3
CCl3
22
24
Figure 3. Mechanistic explanation of oxazoline 24 formation.
both 5-exo-trig and 6-endo-trig cyclisations. An evidence has been
recently provided that C–N bond formation is rate limiting
(first irreversible step) in the rearrangement of allylic tri-
chloroacetimidates to amides, e.g., 22.7 It cannot be excluded,
however, that for oxazoline 24 formation de-oxymetallation is the
first irreversible step due to lower ability of methanol to serve as
a leaving group in intermediate 34 compared to protonated imidate
in 33. In this case, not only 5-exo-trig and 6-endo-trig cyclisations
but also de-aminometallation and de-oxymetallation rates of
intermediate 34 may determine the products 22 and 24 ratio.
Although such a product formation has not been reported pre-
viously in ether-directed diastereoselective Overman rearrange-
ment, vinyloxazoline has been isolated as the major product in the
metal catalysed rearrangement of trichloroacetimidate derived
from Z-(3-benzyloxy)crotyl alcohol or bis-trichloroacetimidate
from Z-but-2-ene-1,4-diol.5,6 In analogy to the CIR mechanism of
the Overman rearrangement, we hypothesise that oxazoline 24
results from the metal ion induced 5-exo-trig cyclisation to ami-
nometallation intermediate 34 and a subsequent de-oxymetalation
step in which methanol elimination regenerates the catalyst in the
original oxidation state (Fig. 3). It is puzzling why the 5-exo-trig
cyclisation product is observed with d-oxy substituted tri-
chloroacetimidates while it has never been observed as a dominant
side reaction for d-unsubstituted allylic trichloroacetimidates that
should give b-hydride elimination product with Pd(0) formation.
One of the explanations would be that the imidate nitrogen attack
at C-2 is driven by the electronic effect of the d-oxygen assuming
intermolecular aminometallation as the first irreversible step for
3. Conclusions
In summary, we have shown that for both d-methoxy and
d-TBDMSO substituted trichloroacetimidates the use of PtCl2 catalyst
gives notably improved anti/syn-ratio of 1,2-aminoalcohol de-
rivatives compared to all metalcatalystsknowntopromote Overman
rearrangement. The formation of 2-trichloromethyloxazoline was
observed as a dominant side reaction reducing the yield of Overman
rearrangement product. This side reaction was suppressed by using
a d-TBDMS-ether as a directing group. For the PtCl2 catalysed rear-
rangement of such substrates, both the yield and improved anti/syn-
ratio of the resulting protected 1,2-aminoalcohols are satisfactory to
be used as a synthetic method. Further investigation to understand
factors determining formation of Overman rearrangement product
versus 2-trichloromethyloxazoline formation is underway.
4. Experimental section
4.1. General
Table 4
Rearrangement of trichloroacetimidates 26–28
Entry
Imidate
Catalyst
Yield of
29–31 (%)
Ratioa
(anti/syn)
Reagents and starting materials were obtained from commercial
sources and used as-received. The solvents were purified and dried
by standard procedures prior to use; petroleum ether of boiling
range 60–80 ꢀC was used. All reactions were performed under an
argon atmosphere. Flash chromatography was carried out using
Merck Kieselgel (230–400 mesh). Thin layer chromatography was
performed on silica gel and was visualised by staining with KMnO4.
NMR spectra were recorded on Varian Mercury spectrometer (400
1.
2.
3.
4.
5.
6.
26, R¼n-Bu
27, R¼Ph
PtCl2
PdCl2
PtCl2
PdCl2
PtCl2
PdCl2
71
65
22
18
<5
d
6:1
3:1
3:1
2:1
2:1
d
28, R¼i-Pr
a
According to GC analysis of crude reaction mixture.

I. Jaunzeme, A. Jirgensons / Tetrahedron 64 (2008) 5794–5799
5797
and 200 MHz) with chemical shifts values (d) in parts per million
(ppm) relative to TMS using residual chloroform signal as internal
standard. Gas chromatographic analysis was performed using HP
6890 gas chromatographic system with HP 5972 MSD detector.
Optical rotations were measured on a Perkin–Elmer 141 polarim-
eter. IR spectra were measured on a Shimadzu FTIR IR Prestige-21
spectrometer.
4.2.5. (E)-(S)-4-Methoxypent-2-enoic acid ethyl ester (10)
LiAlH4 (1.82 g, 0.048 mol) was suspended in Et2O (100 mL) and
the mixture cooled to 0 ꢀC. The solution of methyl (S)-2-meth-
oxypropanoate (5) (5.6 g, 0.048 mol) in Et2O (10 mL) was added
dropwise and the reaction mixture was stirred at room tempera-
ture for 1 h. Water was added to the reaction mixture until white
precipitate has formed. The precipitate was filtered through a pad
of CeliteÒ, which was washed with Et2O. The filtrate was dried
(Na2SO4) and concentrated in vacuo. The (S)-2-methoxypropanol
obtained was used without further purification.
Dimethyl sulfoxide (3.26 mL, 0.046 mol) was added to a solution
of oxalyl chloride (1.97 mL, 0.022 mol) in CH2Cl2 (100 mL) at
ꢁ78 ꢀC. The resulting solution was stirred for 15 min and then (S)-
2-methoxypropanol solution in CH2Cl2 (120 mL) was added. This
solution was allowed to stir for additional 15 min. Triethylamine
(13.44 mL) was then added and the reaction mixture brought to
room temperature over 2 h. Aldehyde obtained from (S)-
2-methoxypropanol was used for the next transformation without
isolation from reaction mixture.
In a separate flask, sodium hydride (60% in mineral oil) (3.12 g,
0.078 mol) was washed with hexane (2ꢂ15 mL) and suspended in
THF (50 mL). Triethyl phosphonoacetate (16 mL, 0.08 mol) was
added and the mixture was allowed to stir for 40 min. The depro-
tonated phosphonoacetate solution was slowly added to the alde-
hyde solution at 0 ꢀC and the reaction mixture was allowed to stir
for 2 h at room temperature. The reaction mixture was then diluted
with CH2Cl2 (50 mL) and quenched with brine. The organic phase
was separated, dried (Na2SO4) and concentrated in vacuo. Purifi-
cation was performed by flash chromatography on silica gel eluting
with a mixture of petroleum ether and ethyl acetate (4:1) to give
the title compound (1.9 g, 25% over three steps).
4.1.1. (S)-2-Methoxypropionic acid methyl ester (5)
Sodium hydride (60% in mineral oil) (1.2 g, 0.03 mol) was
washed with hexane (2ꢂ5 mL). The powder was suspended in THF
(22 mL) and cooled to 0 ꢀC, and the solution of methyl (S)-lactate 1
(2.6 g, 0.025 mol) in THF (10 mL) was added dropwise. After stirring
for 0.5 h, methyl iodide (4.26 g, 0.03 mol) was added and the
reaction mixture was warmed to room temperature and stirred for
4 h. To the reaction mixture, NH4Cl solution (50 mL) was added and
the resulting mixture extracted with diethyl ether (2ꢂ50 mL). The
organic layers were combined and washed with brine (20 mL),
dried (Mg2SO4) and concentrated in vacuo to yield 1.49 g (50%) of
the title compound as colourless oil.
Spectroscopic data is identical to that reported in the literature.8
4.2. Generalprocedure for thepreparationofTBDMSethers6–9
To the solution of a-hydroxy ester (18.7 mmol) in CH2Cl2
(23 mL), imidazole (19.6 mmol) and tert-butyldimethylsilyl chlo-
ride (19.6 mmol) were added. The reaction mixture was stirred at
room temperature for 24 h and then water (40 mL) was added. The
organic layer was separated and the aqueous layer extracted with
CH2Cl2 (2ꢂ25 mL). The organic extracts were combined, dried
(Na2SO4) and concentrated in vacuo. Purification of the product was
performed by means of flash chromatography on silica gel eluting
with a mixture of petroleum ether and ethyl acetate (15:1).
Spectroscopic data is identical to that reported in the
literature.4a
4.2.6. (E)-(S)-4-(tert-Butyldimethylsilanyloxy)pent-2-enoic acid
ethyl ester (11)
4.2.1. (S)-2-(tert-Butyldimethylsilanyloxy)propionic
acid methyl ester (6)
To the solution of methyl ester 6 (3.0 g, 0.0137 mol) in Et2O
(60 mL) at ꢁ78 ꢀC, 1 M DIBAL-H solution in hexane (14 mL) was
added dropwise and the reaction mixture was allowed to stir at
ꢁ78 ꢀC for 2 h. The reaction was quenched with MeOH (4 mL) and
allowed to warm to room temperature. This mixture was treated
with brine (70 mL) and the aqueous phase was separated and
extracted with Et2O (3ꢂ50 mL). The combined organic phase was
washed with brine (50 mL) and dried (Na2SO4). The crude aldehyde
was obtained after filtration and concentration in vacuo and was
used further without purification.
Solution of triethyl phosphonoacetate (3.07 g, 0.0137 mol) in
Et2O (20 mL) was added dropwise to a suspension of sodium
hydride (60%, 0.55 g, 0.0137 mol) in Et2O (30 mL). To this mixture
was added the solution of crude aldehyde in Et2O (20 mL) and the
mixture stirred at room temperature overnight. After addition of
water (70 mL), the product was extracted with Et2O, dried over
Na2SO4 and purified by flash chromatography on silica gel eluting
with a mixture of petroleum ether and ethyl acetate (20:1) to give
the title compound in 67% (2.3 g) yield as a colourless oil; [a]2D0 þ4.2
(c 3.0, CHCl3) {lit.4a [a]D21 þ4.4 (c 1.0, CHCl3)}. Spectroscopic data is
identical to that reported in the literature.4a
Yield: 4.04 g (99%); colourless oil; [a]2D0 ꢁ27.7 (c 2.0, CCl4) {lit.8
[a]D ꢁ26.9 (c 1.9, CCl4)}. Spectroscopic data is identical to that
reported in the literature.9
4.2.2. 2-(tert-Butyldimethylsilanyloxy)hexanoic acid ethyl ester (7)
Yield: 4.05 g (79%); colourless oil; nmax (neat): 2953, 2927, 2856,
1753, 1733, 1471, 1251, 1143; dH (400 MHz, CDCl3): 4.10–4.25 (3H, m,
Et CH2 and OCH), 1.65–1.75 (2H, m) and 1.25–1.45 (4H, m, n-Bu
(CH2)3), 1.27 (3H, t, J 7.2 Hz, Et CH3), 0.85–0.95 (12H, m, n-Bu CH3
and SiC(CH3)3), 0.08 (3H, s, SiCH3) and 0.05 (3H, s, SiCH3); dC
(100 MHz, CDCl3): 174.0, 72.3, 60.6, 34.9, 27.3, 25.7, 22.4, 18.3, 14.2,
13.9, ꢁ4.9 and ꢁ5.3; m/z (EI): 259 (MþꢁCH3, 1%), 217 (53), 201 (30),
189 (72), 161 (10), 145 (25), 115 (19), 103 (36), 75 (100), 59 (30) and
45 (15).
4.2.3. (tert-Butyldimethylsilanyloxy)phenylacetic acid
methyl ester (8)
Yield: 5.14 g (98%); colourless oil. Spectroscopic data is identical
to that reported in the literature.10
4.2.4. (S)-2-(tert-Butyldimethylsilanyloxy)-3-methylbutyric acid
methyl ester (9)
4.3. General procedure for the preparation of a,b-unsaturated
methyl esters 12–14
Yield: (96%); colourless oil; [a]2D0 ꢁ31.3 (c 2.0, CCl4); nmax (neat):
2953, 1755, 1471, 1387, 1250, 1188, 1145, 1070, 1005; d (200 MHz,
H
CDCl3): 3.97 (1H, d, J 5.2 Hz, OCH), 3.71 (3H, s, CO2CH3), 2.02 (1H, m,
i-Pr CH), 0.85–0.95 (15H, m, i-Pr (CH3)2 SiC(CH3)3), 0.05 (3H, s,
SiCH3) and 0.04 (3H, s, SiCH3); dC (100 MHz, CDCl3): 174.0, 77.1, 51.5,
32.8, 25.7, 19.0, 17.0, ꢁ5.1 and ꢁ5.4; m/z (EI): 231 (MþꢁCH3, 1%), 189
(48), 161 (24), 131 (10), 89 (100), 73 (47), 59 (36) and 41 (15).
The reductions of esters 7–9 to aldehydes were performed as in
the case of TBDMS-protected ester 6 using 1 M DIBAL-H solution.
The crude aldehyde (w1 mmol) was taken up in toluene (3 mL) and
methyl (triphenylphosphoranylidene)acetate (1 mmol) was added.
The reaction mixture was refluxed for 30 min, cooled to room

5798
I. Jaunzeme, A. Jirgensons / Tetrahedron 64 (2008) 5794–5799
temperature and concentrated in vacuo. The residue was purified
by flash chromatography on silica gel eluting with a mixture of
petroleum ether and ethyl acetate (20:1).
4.4.4. (E)-4-(tert-Butyldimethylsilanyloxy)-4-
phenylbut-2-en-1-ol (18)
Yield: 0.25 (89%); colourless oil; n
(neat): 3327, 2950, 2924,
max
2852, 1741, 1600, 1469, 1360, 1251, 1093, 1057, 1002; dH (400 MHz,
CDCl3): 7.20–7.35 (5H, m, Ph), 5.75–5.90 (2H, m, HC]CH), 5.19 (1H,
d, J 5.3 Hz, OCH), 4.14 (2H, m, OCH2), 1.26 (1H, m, OH), 0.90 (9H, s,
4.3.1. (E)-4-(tert-Butyldimethylsilanyloxy)oct-2-enoic
acid methyl ester (12)
Yield: 72%; colourless oil; n
(neat) 2956, 2931, 2859, 1730,
SiC(CH3)3), 0.06 (3H, s, SiCH3), ꢁ0.02 (3H, s, SiCH3); d (100 MHz,
max
C
1661, 1463, 1274, 1259, 1165, 1092 cmꢁ1; dH (200 MHz, CDCl3): 6.94
(1H, dd, J 15.5, 4.5 Hz, ]CH), 5.98 (1H, dd, J 15.4, 1.7 Hz, ]CH),
4.25–4.35 (1H, m, OCH), 3.74 (3H, s, CO2CH3), 1.50–1.60 (2H, m) and
1.25–1.35 (4H, m, n-Bu (CH2)3), 0.80–1.00 (12H, m, n-Bu CH3 and
Si(C(CH3)3)), 0.03 (3H, s, SiCH3) and 0.05 (3H, s, SiCH3); dC (100 MHz,
CDCl3): 167.2, 151.5, 119.2, 71.5, 51.5, 37.0, 26.9, 25.8, 22.7, 18.2, 14.0,
ꢁ4.6 and ꢁ4.9; m/z (EI): 286 (Mþ, 1%), 229 (71), 197 (40), 129 (10),
89 (100), 81 (23), 73 (78), 59 (32) and 41 (33).
CDCl3): 143.7, 135.3, 128.2, 128.0, 127.1, 125.9, 74.8, 63.1, 25.8, 18.3,
ꢁ4.6 and ꢁ4.8; m/z (EI): 221 (Mþꢁt-Bu, 3%), 129 (50), 115 (7), 91
(13), 75 (100), 57 (8) and 41 (13).
4.4.5. (E)-(S)-4-(tert-Butyldimethylsilanyloxy)-5-
methylhex-2-en-1-ol (19)
Yield: 0.24 g (99%); colourless oil; [a]2D0 þ2.8 (c 3.0, CHCl3).
Spectroscopic data is identical to that reported in the literature.9
4.3.2. (E)-4-(tert-Butyldimethylsilanyloxy)-4-phenylbut-2-enoic
acid methyl ester (13)
4.5. General procedure for the preparation of
trichloroacetimidates 20, 21, and 26–28
Yield: 60%; colourless oil; n
(neat) 2952, 2930, 2858, 1726,
max
1659, 1436, 1298, 1279, 1259, 1193, 1165, 1125 cmꢁ1; dH (400 MHz,
CDCl3): 7.05–7.35 (5H, m, Ph), 6.98 (1H, dd, J 15.5, 4.5 Hz, ]CH), 6.12
(1H, dd, J 15.5, 2.0 Hz, ]CH), 5.31 (1H, dd, J 4.2, 1.8 Hz, OCH), 3.72
(3H, s, CO2CH3), 0.91 (9H, s, SiC(CH3)3), 0.06 (3H, s, SiCH3) and ꢁ0.06
Sodium hydride (60% in mineral oil) (10 mol %) was added to
a solution of allylic alcohol 15–19 (10 mmol) in Et2O (15 mL). The
reaction mixture was cooled to ꢁ10 ꢀC and a solution of tri-
chloroacetonitrile (11 mmol) in diethyl ether (10 mL) was added
dropwise. The solution was allowed to warm to room temperature
and the solvent was evaporated. Light petroleum ether (20 mL)
containing methanol (0.1 mL) was added to the residue. The solu-
tion was filtered through a pad of CeliteÒ, evaporated and used
without further purification.
(3H, s, SiCH3); d (100 MHz, CDCl3): 167.1, 150.6, 141.6, 128.5, 127.7,
C
126.2, 118.4, 74.1, 51.5, 25.7, 18.3, ꢁ4.9 and ꢁ4.9; m/z (EI): 291
(MþꢁCH3, 1%), 249 (45), 173 (7), 115 (100), 89 (59), 75 (23), 59 (15)
and 41 (10).
4.3.3. (E)-(S)-4-(tert-Butyldimethylsilanyloxy)-5-methylhex-2-
enoic acid methyl ester (14)
Yield: 62%; colourless oil; [a]2D0 þ2.0 (c 2.0, CCl4) {lit.9 [a]D þ1.0
(c 1.0, CHCl3)}. Spectroscopic data is identical to that reported in the
literature.9
4.5.1. 2,2,2-Trichloroacetimidic acid (E)-(S)-4-methoxy-
pent-2-enyl ester (20)
Yield: 2.42 g (93%); colourless oil; dH (200 MHz, CDCl3): 8.32
(1H, br s, NH), 5.70–5.95 (2H, m, HC]CH), 4.14 (2H, d, J 4.5 Hz,
OCH2), 3.78 (1H, m, OCH), 3.29 (3H, s, OCH3), 1.26 (3H, d, J 6.5 Hz,
CH3).
4.4. General procedure for the preparation of allylic alcohols
15–19
The solution of unsaturated ester (1 mmol) in Et2O (20 mL) was
cooled to ꢁ78 ꢀC and 1 M DIBAL-H solution in hexane (2.2 equiv)
was added dropwise. The reaction mixture was allowed to stir at
ꢁ78 ꢀC for 2 h and then warmed to room temperature. A solution of
Rochelle salt (30 mL) was added and stirred until the phases have
separated. The aqueous phase was separated and extracted with
Et2O (2ꢂ20 mL). The combined organic phase was washed with
brine (50 mL), dried over Na2SO4 and purified by flash chroma-
tography on silica gel eluting with a mixture of petroleum ether and
ethyl acetate (20:1).
4.5.2. 2,2,2-Trichloroacetimidic acid (E)-(S)-4-(tert-butyldi-
methylsilanyloxy)pent-2-enyl ester (21)
Yield: 3.71 g (99%); colourless oil; d (200 MHz, CDCl3): 8.29
H
(1H, br s, NH), 5.75–5.95 (2H, m, CH]CH), 4.79 (2H, d, J 4.5 Hz,
OCH2), 4.25–4.40 (1H, m, OCH), 1.23 (3H, d, J 6.5 Hz, CH3), 0.89 (9H,
s, SiC(CH3)3), 0.06 (3H, s, SiCH3) and 0.05 (3H, s, SiCH3).
4.5.3. 2,2,2-Trichloroacetimidic acid (E)-4-(tert-butyldi-
methylsilanyloxy)oct-2-enyl ester (26)
Yield: 4.12 g (99%); colourless oil; dH (200 MHz, CDCl3): 8.28
(1H, br s, NH), 5.70–5.95 (2H, m, CH]CH), 4.79 (2H, d, J 5.0 Hz,
OCH2), 4.05–4.20 (1H, m, OCH), 1.20–1.55 (6H, m, n-Bu (CH2)3),
0.80–0.95 (3H, m, n-Bu CH3), 0.89 (9H, s, SiC(CH3)3), 0.04 (3H, s,
SiCH3), 0.02 (3H, s, SiCH3); dC (100 MHz, CDCl3): 69.1, 72.6, 91.5,
122.2, 139.2, 162.5, 37.7, 27.3, 25.9, 22.6, 18.2, 14.1, ꢁ4.3 and ꢁ4.8.
4.4.1. (E)-(S)-4-Methoxypent-2-en-1-ol (15)
Yield: 0.07 g (61%); colourless oil. Spectroscopic data is identical
to that reported in the literature.4a
4.4.2. (E)-(S)-4-(tert-Butyldimethylsilanyloxy)pent-2-en-1-ol (16)
Yield: 0.17 g (79%); colourless oil; [a]2D0 þ3.6 (c 3.0, CHCl3) {lit.4a
[a]1D9 þ3.7 (c 3.0, CHCl3)}. Spectroscopic data is identical to that
reported in the literature.4a
4.5.4. 2,2,2-Trichloroacetimidic acid (E)-4-(tert-butyldi-
methylsilanyloxy)-4-phenylbut-2-enyl ester (27)
Yield: 3.89 g (89%); colourless oil; d (200 MHz, CDCl3): 8.29
H
(1H, br s, NH), 7.20–7.35 (5H, m, Ph), 5.90–6.00 (2H, m, CH]CH),
5.20–5.25 (1H, m, OCH), 4.75–4.85 (2H, m, OCH2), 0.91 (9H, s,
SiC(CH3)3), 0.07 (3H, s, SiCH3) and ꢁ0.01 (3H, s, SiCH3).
4.4.3. (E)-4-(tert-Butyldimethylsilanyloxy)oct-2-en-1-ol (17)
Yield: 0.24 g (92%); colourless oil; n
(neat) 3600–3100 (br),
max
2957, 2930, 2859, 1473, 1463, 1361, 1256, 1083, 1006 cmꢁ1; d
H
(400 MHz, CDCl3): 5.60–5.80 (2H, m, HC]CH), 4.10–4.15 (2H, m,
OCH2), 1.40–1.55 (2H, m) and 1.25–1.35 (4H, m, n-Bu (CH2)3), 0.85–
0.95 (12H, m, n-Bu CH3 and Si(C(CH3)3)), 0.05 (3H, s, SiCH3) and 0.03
(3H, s, SiCH3); dC (100 MHz, CDCl3): 135.5, 128.2, 72.7, 63.3, 37.9,
27.4, 25.9, 22.7, 18.2, 14.1, ꢁ4.3 and ꢁ4.8; m/z (EI): 243 (MþꢁCH3,
1%), 201 (23), 75 (100), 67 (24) and 41 (23).
4.5.5. 2,2,2-Trichloroacetimidic acid (E)-(S)-4-(tert-butyldi-
methylsilanyloxy)-5-methylhex-2-enyl ester (28)
Yield: 3.22 g (80%); colourless oil; d (200 MHz, CDCl3): 8.28
H
(1H, br s, NH), 5.70–5.90 (2H, m, CH]CH), 3.87 (2H, m, OCH2),
1.60–1.70 (1H, m, CH(CH3)2), 0.80–0.90 (15H, s, CH(CH3)2 and
SiC(CH3)3), 0.03 (3H, s, SiCH3) and ꢁ0.01 (3H, s, SiCH3).

I. Jaunzeme, A. Jirgensons / Tetrahedron 64 (2008) 5794–5799
5799
4.6. General procedure for the Overman rearrangement
(EI): 346 (Mþꢁt-Bu, 15%), 220 (39), 201 (78), 183 (15), 145 (15), 115
(18), 93 (20), 73 (100), 59 (14) and 41 (10).
To the solution of trichloroacetimidate 20, 21, and 26–28
(1 mmol) in CH2Cl2 (or THF in the case of PtCl4) (0.5 M) under argon
atmosphere, metal catalyst (10 mol %) was added and stirred for
18 h at room temperature. The reaction mixture was filtered
through a pad of FlorisilÒ and the isomers were separated by flash
chromatography on silica gel eluting with a mixture of petroleum
ether and ethyl acetate (10:1).
4.6.6. N-{1-[(tert-Butyldimethylsilanyloxy)-phenylmethyl]-allyl}-
2,2,2-trichloroacetamide (anti-30) and N-{1-[(tert-butyldimethyl-
silanyloxy)-phenylmethyl]-allyl}-2,2,2-trichloroacetamide (syn-30)
Yields are shown in Table 4, entries 3 and 4.
anti-30: white solid, mp 74–76 ꢀC; [Found: C, 51.3; H, 6.0; N, 3.2.
C18H26Cl3NO2Si requires C, 51.13; H, 6.20; N, 3.31%] n
(Nujol):
max
3374 (br), 1699, 1514 and 1044 cmꢁ1; dH (200 MHz, CDCl3):
7.25–7.40 (5H, m, Ph), 6.98 (1H, m, NH), 5.78 (1H, ddd, J 16.8, 11.0
and 6.6 Hz, ]CH), 5.00–5.20 (2H, m, ]CH2), 4.94 (1H, d, J 3.6 Hz,
OCH), 4.57 (1H, m, NCH), 0.94 (9H, s, SiC(CH3)3), 0.09 (3H, s, SiCH3)
and ꢁ0.17 (3H, s, SiCH3); dC (100 MHz, CDCl3): 161.0, 139.8, 131.6,
128.1, 127.9, 126.5, 118.3, 75.8, 59.8, 25.8, 18.1, ꢁ4.5 and ꢁ5.2; m/z
(EI): 366 (Mþꢁt-Bu, 13%), 221 (100), 203 (14), 163 (12), 149 (15), 129
(10) and 73 (53).
4.6.1. 2,2,2-Trichloro-N-[(R)-1-((S)-1-methoxyethyl)-
allyl]acetamide (anti-22)
Yields are shown in Table 2; pale yellow oil; [a]1D9 þ17.5 (c 3.0,
CHCl3). Spectroscopic data is identical to that reported in the
literature.4a
4.6.2. N-{(R)-1-[(S)-1-(tert-Butyldimethylsilanyloxy)-ethyl]-allyl}-
2,2,2-trichloroacetamide (anti-23) and N-{(S)-1-[(S)-1-(tert-
butyldimethylsilanyloxy)-ethyl]-allyl}-2,2,2-trichloroacetamide
(syn-23)
syn-30: colourless oil; dH (200 MHz, CDCl3): 7.25–7.40 (5H, m,
Ph), 7.21 (1H, m, NH), 6.02 (1H, ddd, J 17.6, 9.8 and 4.8 Hz, ]CH),
5.20–5.35 (2H, m, ]CH2), 4.87 (1H, d, J 3.0 Hz, OCH), 4.48 (1H, m,
NCH), 0.93 (9H, s, SiC(CH3)3), 0.07 (3H, s, SiCH3) and ꢁ0.14 (3H, s,
SiCH3).
Yields are shown in Table 3; pale yellow oil. Spectroscopic data is
identical to that reported in the literature.4a
4.6.3. 4-((E)-Propenyl)-2-trichloromethyl-4,5-dihydrooxazole (24)
4.6.7. 4-((E)-Styryl)-2-trichloromethyl-4,5-dihydrooxazole (32)
Yellow oil; nmax (neat): 3421, 2968, 1718, 1654, 1449, 1226 cmꢁ1
;
Yield: 52%dPtCl2, and 44%dPdCl2. Yellow oil; d (200 MHz,
H
d
(400 MHz, CDCl3): 5.78 (1H, dq, J 15.1, 6.4 Hz, ]CH), 5.48 (1H,
CDCl3): 7.25–7.45 (5H, m, Ph), 6.66 (1H, d, J 16.1 Hz, ]CH), 6.19 (1H,
dd, J 16.1 and 8.0 Hz, ]CH), 4.95–5.15 (1H, m, NCH), 4.84 (1H, t, J
H
ddq, J 15.1, 7.6, 1.8 Hz, ]CH), 4.75–4.85 (1H, m, CHO), 4.72 (1H, dd,
J 9.6, 8.2 Hz), 4.29 (1H, t, J 8.2 Hz, CH2N), and 1.73 (3H, dd, J 6.6,
1.8 Hz, CH3); dC (100 MHz, CDCl3): 162.8, 130.1, 128.6, 76.2, 68.6 and
17.8.
9.0 Hz) and 4.43 (1H, t, J 8.0 Hz, OCH2); d (100 MHz, CDCl3): 163.3,
C
136.0, 133.3, 128.6, 128.2, 126.6, 126.6, 76.1 and 68.6; m/z (EI): 291
(Mþ, 4%), 254 (27), 224 (15), 189 (13), 182 (53), 154 (11), 142 (16),
128 (46), 115 (100), 102 (16), 91 (29), 77 (24), 63 (24), 51 (24), 51
(22) and 39 (17).
4.6.4. 2,2,2-Trichloro-N-((E)-1-hydroxymethylbut-2-enyl)-
acetamide (25)
Yields are shown in Tables 2 and 3; white solid, mp 67–69 ꢀC;
[Found: C, 34.3; H, 3.9; N, 5.5. C7H10Cl3NO2 requires C, 34.11; H,
4.09; N, 5.68%] nmax (liquid film): 3302, 2938,1710,1688,1530,1454,
1259, 1032 cmꢁ1; dH (200 MHz, CDCl3): 7.26 (1H, br s, NH),
5.70–5.85 (1H, m, ]CH), 5.45–5.55 (1H, m, ]CH), 4.40–4.50 (1H, m,
NCH), 2.13 (1H, br s, OH), 3.70–3.85 (2H, m, CH2O) and 1.70–1.75
Acknowledgements
The work was supported by a grant from Latvian Council of
Science and European Social Fund within the National Programme
‘Support for the carrying out doctoral study programm’s and post-
doctoral researches’. The authors thank Dr. Juris Fotins for valuable
suggestions during the preparation of the manuscript.
(3H, m, CH3); d (100 MHz, CDCl3): 161.6, 129.7, 126.1, 92.6, 64.3,
C
54.6 and 17.9.
References and notes
4.6.5. N-[2-(tert-Butyldimethylsilanyloxy)-1-vinylhexyl]-2,2,2-
trichloroacetamide (anti-29) and N-[2-(tert-butyldimethyl-
silanyloxy)-1-vinylhexyl]-2,2,2-trichloro-acetamide (syn-29)
Yields are shown in Table 4, entries 1 and 2.
1. (a) Overman, L. E. J. Am. Chem. Soc. 1974, 96, 597–599; (b) Overman, L. E. J. Am.
Chem. Soc. 1976, 98, 2901–2910; (c) Overman, L. E. Acc. Chem. Res. 1980, 13,
218–224; (d) Overman, L. E.; Carpenter, N. E. Organic Reactions; Overman, L. E.,
Ed.; Wiley: Hoboken, NJ, 2005; Vol. 66, pp 653–760.
anti-29: colourless oil; nmax (neat): 3405 (br), 2958, 2873, 1699,
1511, 1329 and 1055 cmꢁ1; dH (200 MHz, CDCl3): 7.00–7.10 (1H, br s,
NH), 5.80 (1H, ddd, J 16.8, 10.2 and 7.3 Hz, ]CH), 5.25–5.40 (2H, m,
]CH2), 4.35–4.45 (1H, m, NCH), 3.75–3.85 (1H, OCH),1.20–1.55 (6H,
m, n-Bu (CH2)3), 0.85–1.00 (3H, m, n-Bu CH3), 0.90 (9H, s, SiC(CH3)3),
2. (a) Anderson, C. E.; Overman, L. E. J. Am. Chem. Soc. 2003, 125, 12412–12413; (b)
Kirsch, S.; Overman, E. L.; Watson, M. P. J. Org. Chem. 2004, 69, 8101–8104.
ˇ
3. (a) Gonda, J.; Helland, A. C.; Ernst, B.; Bellus, D. Synthesis 1993, 729–733; (b)
Doherty, A. M.; Kornberg, B. E.; Reily, M. D. J. Org. Chem. 1993, 58, 795–798.
4. (a) Jamieson, A. G.; Sutherland, A. Org. Biomol. Chem. 2005, 3, 735–736; (b)
Jamieson, A. G.; Sutherland, A. Org. Biomol. Chem. 2005, 3, 3749–3756; (c)
Jamieson, A. G.; Sutherland, A. Org. Biomol. Chem. 2006, 4, 2932–2937; (d)
Jamieson, A. G.; Sutherland, A. Tetrahedron 2007, 63, 2123–2131; (e) Swift, M.
D.; Sutherland, A. Tetrahedron Lett. 2007, 48, 3771–3773; (g) Yoon, Y. J.; Chun,
M. H.; Joo, J. E. Arch. Pharm. Res. 2004, 27, 136–142.
0.09 (3H, s, SiCH3) and 0.10 (3H, s, SiCH3); d (100 MHz, CDCl3):
C
161.6, 135.5, 116.6, 92.9, 69.7, 58.6, 25.7, 21.4, 17.9, ꢁ4.3 and ꢁ4.8;
m/z (EI): 346 (Mþꢁt-Bu, 13%), 260 (15), 218 (38), 201 (82), 183 (12),
145 (13), 115 (19), 93 (18), 73 (100), 59 (14) and 41 (10).
5. Jaunzeme, I.; Jirgensons, A. Synlett 2005, 2984–2986.
6. Sabat, M.; Johnson, C. R. Org. Lett. 2000, 2, 1089–1092.
syn-29: dH (200 MHz, CDCl3): 7.20–7.30 (1H, br s, NH), 5.70–5.85
(1H, m, ]CH), 5.15–5.30 (2H, m, ]CH2), 4.35–4.45 (1H, m, NCH),
3.75–3.85 (1H, OCH), 1.20–1.55 (6H, m, n-Bu (CH2)3), 0.85–1.00 (3H,
m, n-Bu CH3), 0.89 (9H, s, SiC(CH3)3), 0.08 (3H, s, SiCH3) and 0.05
(3H, s, SiCH3)dextracted from the spectra of isomeric mixture; m/z
7. Watson, M. P.; Overman, L. E.; Bergman, R. G. J. Am. Chem. Soc. 2007, 129, 5031–
5044.
8. Stammen, B.; Berlage, U.; Kindermann, R. J. Org. Chem. 1992, 57, 6566–6575.
ˇ
9. Ernst, B.; Oehrlein, R.; Bellus, D.; Gonda, J.; Jeschke, R.; Nubbemeyer, U. Helv.
Chim. Acta 1997, 80, 876–891.
10. Joly, G. D.; Jacobsen, E. N. Org. Lett. 2002, 4, 1795–1798.