Enantiocontrol in intermolecular cyclopropanations: Use of diazosulfonate esters

Article abstract of DOI:10.1039/b412285b

The novel use of α-diazosulfonate esters as alternative cyclopropanating agents to diazoacetates is investigated. The effects of structure of both substrate and ligand on diastereo- and enantioselectivity are studied, and the catalytic ability of different metals is compared. The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2005.

Full text of DOI:10.1039/b412285b

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P A P E R
Enantiocontrol in intermolecular cyclopropanations: use of
diazosulfonate esters
Tao Ye*ab and Congying Zhoub
a Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic
University, Hung Hom, Kowloon, Hong Kong, China. E-mail: bctaoye@inet.polyu.edu.hk
b Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, China
Received (in Montpellier, France) 9th August 2004, Accepted 7th June 2005
First published as an Advance Article on the web 8th July 2005
The novel use of a-diazosulfonate esters as alternative cyclopropanating agents to diazoacetates is
investigated. The effects of structure of both substrate and ligand on diastereo- and enantioselectivity are
studied, and the catalytic ability of different metals is compared.
chiral dirhodium catalysts. We decided to choose the reaction
Introduction
between styrene and diazosulfonate 1 (Scheme 2), since this
had given the most promising anti/syn ratio of products in the
rhodium acetate catalysed reactions, and the results are pre-
sented in Table 2. Doyle’s catalyst,10 Rh2(MEPY)4 gave a
lower yield than the carboxylate-based catalyst previously
employed, but it did give a satisfactory anti/syn ratio of
product (entry 2). However, although the diastereoselectivity
was promising, the products, either syn or anti, were formed as
a racemic mixture. A racemic product was also obtained when
the prolinate ligand11 was used, but this system did not show
any differentiation between syn and anti products (entry 3).
Catalytic carbon–carbon bond-forming reactions have been a
major area of research for some time with advances in these
reactions occurring at pace in the areas of oxidation, reduction
and addition. A versatile source of such reactions is transfor-
mations involving metal-carbenes derived from diazocarbonyl
compounds, and we have been involved with their chemistry
for more than a decade.1 The metal-carbenes undergo a range
of insertion and cycloaddition reactions, governed in some part
by the metal involved.1–3 Much work has been published on
systems utilising ethyl diazoacetate for cyclopropanation reac-
tions, with both rhodium4 and copper catalysts,1–3 and this
reaction is seen as the benchmark system for testing catalyst
design. The copper catalysts have proven to be more effective
at inducing asymmetry in this reaction, with particularly high
selectivity achieved by the bisoxazoline (BOX) ligands.5 De-
spite a plethora of papers on diazoacetate insertions, few have
mentioned work with heteroatom esters. To the best of our
knowledge, the only papers mentioning the reaction of
a-diazosulfonates have been under photolysis6 or thermolysis
conditions.7 Here we discuss our findings on metal catalysed
cyclopropanation reactions involving a-diazosulfonate esters.
12
Use of the catalyst Rh2(PTTL)4 showed a slight preference
for the syn product and also a moderate degree of asymmetric
induction in each product (entry 4). When the axially-chiral
ligands based on the biphenyl structure13 were used, the
preference for the syn isomer was again seen, with varying
amounts of asymmetric induction observed.14 The methyl
(entry 5), tert-butyl (entry 6) and benzyl (entry 7) monoesters
of (S)-4,40,5,50,6,60-hexamethoxy-2,20-diphenic acid were all
employed as ligands for the dirhodium catalysts. The best
results, in terms of both diastereo- and enantioselectivity, were
Results and discussion
A range of diazosulfonates was produced following Danhei-
ser’s method,8 and these were initially reacted with a series of
alkenes in the presence of dirhodium tetraacetate (Scheme 1).
This catalyst readily effected the decomposition of the diazo-
sulfonate, and the corresponding cyclopropane–sulfonic acid
derivative was isolated in good to excellent yield (Table 1).
Although the yields for these reactions were generally good, the
syn/anti selectivity9 exhibited by the catalyst was modest. The
general trend was for the anti product to be favoured, although
the best selectivity for this was only 2.9 : 1 (entry 11). Entries
1–5 suggest that the reagent has considerably less influence on
the diastereoselectivity than the structure of the substrate, with
each of the reagents giving a similar ratio of anti : syn products
with styrene. The non-aromatic substituted alkenes showed a
wide difference in the selectivity in this reaction: ethyl vinyl
ether showed only a slight preference for the anti product
(entry 10), whereas the tertiary butyl vinyl ether showed the
highest proportion of anti product (entry 11).
Scheme 1
Table 1 Cyclopropanation of various alkenes
Entry
R1
R2
Yield/%
Anti : Syn
1
Ph
Ph
CH3CH2
67
81
91
62
83
85
89
86
69
86
83
42
1.5 : 1
1.6 : 1
1.6 : 1
1.9 : 1
1.5 : 1
1.2 : 1
1.4 : 1
1.5 : 1
2.4 : 1
1.1 : 1
2.9 : 1
2.1 : 1
2
PhCH2CH2
Me2CHCH2
(Me2CH)2CH
Me3CCH2
Me3CCH2
Me3CCH2
Me3CCH2
Me3CCH2
Me3CCH2
Me3CCH2
Me3CCH2
3
Ph
Ph
4
5
Ph
6
p-OMe-Ph
p-Me-Ph
p-Cl-Ph
m-NO2-Ph
EtO
7
8
9
10
11
12
Me3CO
MeCO2CH2
Having observed only a modest diastereoselectivity in the
reaction, we investigated the enantioselectivity by using homo-
T h i s j o u r n a l i s & T h e R o y a l S o c i e t y o f C h e m i s t r y a n d t h e
C e n t r e N a t i o n a l d e l a R e c h e r c h e S c i e n t i f i q u e 2 0 0 5
N e w J . C h e m . , 2 0 0 5 , 2 9 , 1 1 5 9 – 1 1 6 3
1159

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and reduced enantioselectivity for each of the product isomers
(entry 8). Vinyl acetate gave a higher proportion of anti
product, and gave this product in greater than 99% ee (entry
9).14 Examining the preference for a particular isomer and
relating this to reactant structure readily explains the selectivity
shown in these reactions. In terms of the substrate, an electron-
deficient alkene has exhibited the best anti : syn ratio. This is
probably due to the electrophilic carbene species reacting less
readily with it, and therefore being more sensitive to steric
factors. In contrast, the electron-rich vinyl ether (Table 1, entry
10) showed virtually no selectivity in terms of product geome-
try. A bulky substituent on the alkene also encourages more
anti product to form, but the selectivity was relatively low.
Fig. 1
Scheme 2
Table 2 Cyclopropanations using different catalysts
Conclusion
Entry Catalyst
Yield/% anti : syn anti (ee%) Syn (ee%)
We have shown that a-diazosulfonates may be used as versatile
alternatives to diazoacetates. The behaviour of the diazosulfo-
nates is similar to the diazoacetates insofar as the anti product
is generally favoured, although this is somewhat influenced by
the catalyst employed for the decompositions. The reactions
proceed much more favourably with the copper catalyst than
the rhodium ones and again, this mirrors the results of the
analogous acetates. Rhodium catalysed reactions showed mod-
erate selectivity, but when copper was employed as the catalyst
far superior selectivities were observed, in terms of both
relative and absolute stereochemistry. The BOX ligands, which
have proven to be very versatile and effective ligands in a range
of different metal-mediated reactions, have proven to be so
again in this reaction.
1
2
3
4
5
6
7
8
Rh2(OAc)4
83
44
82
85
1.5 : 1
2.8 : 1
1.0 : 1
1 : 1.3
1 : 1.2
1 : 1.2
1 : 2.0
6.1 : 1
—
0
—
0
a
b
c
0
0
29
15
20
38
92
25
4
d (R ¼ Me) 80
d (R ¼ But) 84
7
d (R ¼ Bn)
60
90
15
79
e
obtained when the benzyl ester was used, but the selectivity was
still disappointingly moderate on each count.
Moving from rhodium to copper, using the Cu(I)BOX
catalyst (entry 8), the preference for the anti product was quite
marked, and on analysing the product (chiral HPLC),14 the
anti cyclopropane was found to have an ee of 92%. Encoura-
gingly, the minor syn isomer was found to have an ee of 79%,
and the combined yield of 90% emphasised that this catalyst
was by far the best performer of those tried.
Experimental
General procedure for preparation of alkyl a-
diazomethanesulfonate
To a solution of alkyl methanesulfonate (15 mmol) in dry THF
(50 mL) was added a 1 M LiHMDS solution in hexane (18 mL,
18 mmol) at ꢀ78 1C. After stirring the reaction mixture for 30
min at this temperature, 2,2,2-trifluoroethyl trifluoroacetate
(2.4 mL, 18 mmol) was added rapidly in one portion via syringe
(over about 5 s.). After 10 min, the reaction mixture was
poured into a solution of diethyl ether (20 mL) and 5%
hydrochloric acid (40 mL). The mixture was extracted with
diethyl ether (200 mL), washed with brine, dried over Na2SO4,
filtered and concentrated under reduced pressure using a rotary
evaporator to give a yellow oil. This yellow oil was immediately
dissolved in CH3CN (30 mL). To this solution was added
4-acetamidobenzenesulfonyl azide (4.32 g, 18 mmol), Et3N
(2.5 ml, 18 mmol), and water (0.27 mL, 15 mmol). After
stirring the reaction mixture overnight at rt, the solvent was
removed under reduced pressure using a rotary evaporator.
The residue was filtered on short silica gel and washed with a
mixture of ethyl acetate (100 mL) and hexane (100 mL). The
filtrate was concentrated under vacuum and the residue was
purified by flash chromatography on silica gel to afford the
desired product.
Given these encouraging results, we decided to use the
Cu(I)BOX catalyst for some of the earlier transformations
and the results are shown in Table 3. In each case, the copper
catalyst showed a greater selectivity for the anti isomer over the
syn isomer. More importantly, the enantioselectivity shown
was very high. The examples with para-substituted styrenes
(entries 2–4) gave moderate to good diastereoselectivity, and
very good enantioselectivities in both the syn and anti isomers,
while meta-nitrostyrene (entries 5 and 6) showed almost total
selectivity in both isomers, albeit at the expense of overall yield.
Reaction of the sulfonate with 1,1-diphenylethene (entry 7)
proceeded to give the cyclopropanesulfonate ester almost en-
antio-specifically. Cyclopropanation of tert-butyl vinyl ether
proceeded to give a moderate preference for the anti isomer
Scheme 3
( )
Table 3 Cyclopropanations mediated by Cu I (BOX)
Entry
R1
R2
R3
Yield%
anti : syn
anti (ee%)
syn (ee%)
1
2
3
4
5
6
7
8
9
Me3CCH2
Me3CCH2
Me3CCH2
Me3CCH2
Me3CCH2
(Me2CH)2CH
Me3CCH2
Me3CCH2
Me3CCH2
Ph
H
H
H
H
H
H
Ph
H
H
90
87
92
85
69
65
43
81
34
6.1 : 1
5.1 : 1
4.1 : 1
5.9 : 1
9.2 : 1
11.4 : 1
—
92
90
79
90
85
88
97
—
—
91
—
p-Me-C6H4
p-MeO-C6H4
p-Cl-C6H4
m-NO2-C6H4
m-NO2-C6H4
Ph
89
90
499
499
499
77
Me3CO
MeCO2CH2
3.1 : 1
4.5 : 1
499
1160
N e w J . C h e m . , 2 0 0 5 , 2 9 , 1 1 5 9 – 1 1 6 3

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J ¼ 8.5, 6.6, 5.6 Hz), 1.80(dt, 1H, 9.8, 5.6 Hz), 2.67(ddd, 1H, J
2,2-Dimethylpropyl a-diazomethanesulfonate. This com-
pound was obtained as a yellow oil (60%). 1H NMR (300
MHz, CDCl3) dH 0.96(s, 9H), 3.79(s, 2H), 5.26(s, 1H). 13C
NMR (75 MHz, CDCl3) dC, 79.9, 51.9, 31.5, 25.8. IR (neat)
3096, 2967, 2106, 1468, 1367, 1273, 1145, 956, 829
¼ 8.5, 5.6, 4.5 Hz), 2.80(ddd, 1H, J ¼ 9.8, 6.6, 4.5 Hz), 4.34(q,
2H, J ¼ 7.1 Hz), 7.12–7.36(m, 5H). 13C NMR (75 MHz,
CDCl3) dC, 137.1, 128.7, 127.3, 126.5, 66.7, 36.3, 23.3, 15.1,
13.8. IR (neat) 2922, 1351, 1168, 1004, 916. MS (EI): 226(M1,
2), 117(100). HRMS (EI): calcd for C11H14O3S 226.0663,
1
found 226.0656. syn-isomer: H NMR (400 MHz, CDCl3) dH
2-Methylpropyl a-diazomethanesulfonate. This compound
was obtained as a yellow oil (48%). 1H NMR (270 MHz,
CDCl3) dH 1.00(d, 6H, J ¼ 6.9 Hz), 2.02(m, 1H), 3.95(d, 2H,
J ¼ 6.6 Hz), 5.29(s, 1H). 13C NMR (67.8 MHz, CDCl3)
dC.76.7, 52.1, 27.8, 18.5. IR(neat) 2966, 2117, 1472, 1355,
1170, 975. MS (EI): 150(M1 ꢀ N2, 8). HRMS (EI): calcd for
C5H10O3S 150.0350, found 150.0346.
1.27(t, 3H, J ¼ 7.1 Hz), 1.64(td, 1H, J ¼ 8.6, 5.6 Hz), 1.97(dt,
1H, J ¼ 8.0, 5.6 Hz), 2.73(q, 1H, J ¼ 8.5 Hz), 2.81(td, 1H, J ¼
8.6, 5.6 Hz), 4.06(dq, 2H, J ¼ 7.1, 1.2 Hz), 7.24–7.38(m, 5H).
13C NMR (100 MHz, CDCl3) dC, 133.3, 129.5, 128.0, 127.4,
65.9, 35.1, 23.7, 15.0, 10.6. IR (neat) 2919, 1350, 1167, 1003,
899. MS (EI): 226(M1, 3), 160(4), 117(100). HRMS (EI): calcd
for C11H14O3S, 226.0663, found 226.0664.
Ethyl a-diazomethanesulfonate. This compound was ob-
tained as a yellow oil (40%). 1H NMR (300 MHz, CDCl3)
2-Phenylethyl 2-phenylcyclopropanesulfonate. anti-isomer. 1H
NMR (300 MHz, CDCl3) dH 1.42(dt, 1H, J ¼ 8.5, 6.7 Hz),
1.72(dt, 1H, J ¼ 10.7, 5.6 Hz), 2.52(dt, 1H, J ¼ 8.5, 5.6 Hz),
2.73(ddd, 1H, J ¼ 10.7, 6.7, 4.5 Hz), 3.04(t, 2H, J ¼ 6.9 Hz),
4.45(t, 2H, J ¼ 6.9 Hz), 7.03–7.32(m, 10H). 13C NMR (75
MHz, CDCl3) dC, 137.0, 136.3, 128.9, 128.7, 128.6, 127.2,
126.9, 126.4, 70.5, 36.2, 35.6, 23.3, 13.7. IR (neat) 3010,
2950, 1358, 1168, 958, 696. MS (EI): 302(M1, 2), 117(100),
104(73). HRMS (EI): calcd for C17H18O3S 302.0977, found
302.0974. syn-isomer: 1H NMR (300 MHz, CDCl3) dH 1.52(td,
1H, J ¼ 8.6, 6.1 Hz), 1.91(q, 1H, J ¼ 6.1 Hz), 2.67(dd, 2H, J ¼
8.6, 6.7 Hz), 2.91(t, 2H, J ¼ 7.2 Hz), 4.18(dt, 2H, J ¼ 7.2, 2.0
Hz), 7.12–7.34(m, 10H). 13C NMR (75 MHz, CDCl3) dC,
136.4, 133.2, 129.5, 128.9, 128.5, 128.0, 127.4, 126.9, 69.8,
35.5, 35.0, 23.7, 10.6. IR (neat) 3030, 2959, 1350, 1167, 958,
775, 696. MS (EI): 302(M1, 2), 153(9), 117(100), 104(90).
HRMS (EI): calcd for C17H18O3S 302.0977, found 302.0985.
d
H 1.42(t, 3H, J ¼ 7.2 Hz), 4.26(q, 2H, J ¼ 7.2 Hz), 5.30(s, 1H).
13C NMR (75 MHz, CDCl3) dC, 67.3, 52.1, 14.4. IR(neat)
3102, 2988, 2114, 1346, 1178, 997, 916. MS (EI): 122(M1 ꢀ N2,
100), 92(10), 65(25). HRMS (EI): calcd for C3H6O3S 122.0037,
found 122.0037.
2,4-Dimethyl-3-pentyl a-diazomethanesulfonate. This com-
pound was obtained as a yellow oil (63%). 1H NMR (300
MHz, CDCl3) dH 0.97(d, 6H, J ¼ 4.2 Hz), 1.01(d, 6H, J ¼ 4.2
Hz), 2.03(m, 2H), 4.32(t, 1H, J ¼ 5.7 Hz), 5.30(s, 1H). 13C
NMR (75 MHz, CDCl3) dC, 96.6, 54.8, 30.0, 19.8, 17.5.
IR(neat) 2924, 2111, 1375, 1260, 1092.
2-Phenylethyl a-diazomethanesulfonate. This compound was
1
obtained as a yellow oil (42%). H NMR (300 MHz, CDCl3)
d
H 3.01(t, 2H, J ¼ 6.8 Hz), 4.33(t, 2H, J ¼ 6.8 Hz), 5.04(s, 1H),
7.10–7.33(m, 5H). 13C NMR (75 MHz, CDCl3) dC, 136.1,
128.7, 128.5, 126.8, 71.1, 51.9, 34.9. IR(neat) 3082, 2106,
2-Methylpropyl 2-phenylcyclopropanesulfonate. anti-isomer.
1H NMR (270 MHz, CDCl3) dH 0.96(d, 6H, J ¼ 7.0 Hz),
1.53(ddd, 1H, J ¼ 8.3, 6.6, 5.6 Hz), 1.80(dt, 1H, J ¼ 9.9, 5.6
Hz), 2.04(m, 1H), 2.67(ddd, 1H, J ¼ 8.3, 5.6, 4.6 Hz), 2.78(ddd,
1H, J ¼ 9.9, 6.6, 4.6 Hz), 4.03(d, 1H, J ¼ 6.6 Hz), 7.12–7.34(m,
5H). 13C NMR (67.8 MHz, CDCl3) dC, 137.1, 1287.8, 127.3,
126.5, 76.2, 36.2, 28.2, 23.3, 18.6, 13.7. IR (neat) 2962, 1349,
1160, 968, 829. MS (EI): 254(M1, 3), 153(11), 136(17),
117(100). HRMS (EI): calcd for C13H18O3S 254.0977, found
1446, 1360, 1259, 1165, 956, 754, 694. MS (EI): 198(M1
N2, 5), 122(22), 104(100). HRMS (EI): calcd for C9H10O3S
198.0350, found 198.0345.
ꢀ
General procedure for dirhodium(II) complexes catalyzed
cyclopropanation with alkyl a-diazomethanesulfonates
To a solution of rhodium catalyst (2 mol%) and styrene
(5 equiv) in CH2Cl2 was added a solution of a-diazomethane-
sulfonate in CH2Cl2 by syringe pump over a 2 h period. The
reaction mixture was stirred for an additional 1 h. The solvent
and excess styrene were removed under reduced pressure and
the residue was purified by flash chromatography on silica gel
to afford the desired product.
1
254.0976. syn-isomer: H NMR (270 MHz, CDCl3) dH 0.89(d,
6H, J ¼ 6.6 Hz), 1.62(td, 1H, J ¼ 8.5, 5.6 Hz), 1.89(m, 1H),
2.00(dt, 1H, J ¼ 7.9, 5.6 Hz), 2.74(q, 1H, J ¼ 8.5 Hz), 2.82(td,
1H, J ¼ 8.5, 5.6 Hz), 3.75(d, 1H, J ¼ 6.6 Hz), 7.25–7.39(m,
5H). 13C NMR (67.8 MHz, CDCl3) dC, 133.4, 129.5, 128.0,
127.4, 75.4, 35.1, 28.1, 23.7, 18.6, 10.5. IR (neat) 2965, 1359,
1171, 978. MS (EI): 254(M1, 50), 205(16), 181(24), 153(100),
107(23). HRMS (EI): calcd for C13H18O3S 254.0977, found
254.0971.
General procedure for Cu(I)OTf/bisoxazoline catalyzed
cyclopropanation with alkyl a-diazomethanesulfonates
In an inert-atmosphere box, copper triflate benzene complex
(0.011 g, and 0.0393 mmol of copper) and chiral bisoxazoline
(0.0118 g, 0.0401 mmol) were added to a 10 mL round bottom
flask. After the addition of 3.0 mL of dry chloroform, the
solution was stirred at r.t. for 1 h. The blue-green solution was
then transferred by filter cannula into a flask containing the
styrene in chloroform under nitrogen. A solution of diazosul-
fonate in chloroform was added to the solution of copper
complex and styrene by syringe pump over 2 h. The reaction
mixture was stirred for an additional 1 h, and solvent and
styrene were removed by rotary evaporation. The crude oil was
purified by flash chromatography on silica gel to afford the
desired product.
2,2-Dimethylpropyl 2-ethoxycyclopropanesulfonate. anti-iso-
1
mer. H NMR (300 MHz, CDCl3) dH 0.98(s, 9H), 1.23(t, 3H,
J ¼ 7.0 Hz), 1.45–1.54(m, 2H), 2.54(ddd, 1H, J ¼ 9.3, 6.4, 2.1
Hz), 3.61–3.71(m, 2H), 3.82(ddd, 1H, J ¼ 6.4, 4.6, 2.1 Hz),
3.89(s, 2H). 13C NMR (75 MHz, CDCl3) dC, 79.1, 67.1, 57.2,
33.4, 31.7, 26.0, 14.8, 13.8. IR (neat) 2971, 1344, 1161, 964, 827.
MS (EI): (M1 ꢀ OC5H11, 100), 133(45). HRMS (EI): calcd for
C5H9O3S 149.0272, found 149.0249. syn-isomer: 1H NMR (400
MHz, CDCl3) dH 1.02(s, 9H), 1.27(t, 3H, J ¼ 7.1 Hz), 1.41(dt,
1H, J ¼ 9.3, 6.8 Hz), 1.78(td, 1H, J ¼ 6.8, 5.0 Hz), 2.44(dt, 1H,
J ¼ 9.3, 5.0 Hz), 3.62–3.74(m, 2H), 3.80(m, 1H), 3.91(d, 1H,
J ¼ 9.2 Hz), 3.97(d, 1H, J ¼ 9.2 Hz). 13C NMR (75 MHz,
CDCl3) dC, 79.3, 67.4, 56.6, 33.7, 31.7, 26.1, 14.9, 13.4. IR
(neat) 2974, 1357, 1220, 1172, 969, 836. MS (EI): (M1
OC5H11, 60), 80(100). HRMS (EI): calcd for C5H9O3S
149.0272, found 149.0249.
ꢀ
Ethyl 2-phenylcyclopropanesulfonate. anti-isomer. 1H NMR
(400 MHz, CDCl3) dH 1.41(t, 3H, J ¼ 7.1 Hz), 1.51(ddd, 1H,
N e w J . C h e m . , 2 0 0 5 , 2 9 , 1 1 5 9 – 1 1 6 3
1161

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2-(4-methylphenyl)cyclopropanesulfo-
2,4-Dimethyl-3-pentyl 2-phenylcyclopropanesulfonate. anti-
isomer. 1H NMR (500 MHz, CDCl3) dH 0.99(m, 12H),
1.49(dt, 1H, J ¼ 8.5, 6.6 Hz), 1.80(dt, 1H, J ¼ 10.8, 5.4 Hz),
2.01(m, 2H), 2.71(ddd, 1H, J ¼ 8.5, 5.4, 4.4 Hz), 2.79(ddd, 1H,
J ¼ 10.8, 6.6, 4.4 Hz), 4.36(t, 1H, J ¼ 5.7 Hz), 7.12–7.32(m,
5H). 13C NMR (100 MHz, CDCl3) dC, 137.8, 128.8, 127.3,
126.6, 94.8, 37.8, 30.2, 30.1, 23.5, 20.1, 17.9, 17.7, 14.5. IR
(neat) 2915, 1200, 1159. MS (EI): 296(M1, 3), 181(46),
153(100), 136(57), 117(55), 108(24). HRMS (EI): calcd for
C16H24O3S 296.1446, found 296.1457. syn-isomer: 1H NMR
(400 MHz, CDCl3) dH 0.87(2d, 6H, J ¼ 6.8 Hz), 0.98(2d, 6H,
J ¼ 6.8 Hz), 1.62(td, 1H, J ¼ 8.5, 5.6 Hz), 1.87–1.98(m, 3H),
2.68(q, 1H, J ¼ 8.5 Hz), 2.85(td, 1H, J ¼ 8.5, 5.6 Hz), 4.26(t,
1H, J ¼ 5.6 Hz), 7.22–7.40(m, 5H). 13C NMR (75 MHz,
CDCl3) dC, 133.6, 129.6, 127.9, 127.3, 93.5, 36.2, 30.1, 30.0,
23.9, 20.0, 19.8, 17.8, 17.5, 11.0. IR (neat) 2965, 1350, 1167,
893. MS (EI): 296(M1, 4), 181(53), 117(100). HRMS (EI):
calcd for C16H24O3S 296.1446, found 296.1449.
2,2-Dimethylpropyl
nate. anti-isomer. 1H NMR (400 MHz, CDCl3) dH 0.98(s,
9H), 1.49(dt, 1H, J ¼ 8.5, 6.2 Hz), 1.78(dt, 1H, J ¼ 9.8, 5.3
Hz), 2.33(s, 3H), 2.63(dt, 1H, J ¼ 8.5, 5.3 Hz), 2.75(ddd, 1H,
J ¼ 9.8, 6.2, 4.5 Hz), 3.90(s, 2H), 7.01(d, 2H, J ¼ 8.0 Hz),
7.13(d, 2H, J ¼ 8.0 Hz). 13C NMR (100 MHz, CDCl3) dC,
137.0, 134.1, 129.4, 126.4, 79.4, 36.0, 31.8, 26.0, 23.0, 21.0, 13.6.
IR (neat) 2965, 1343, 1170, 963, 812. MS (EI): 282(M1, 5),
212(19), 195(7), 131(100), 129(5). HRMS (EI): calcd for
C15H22O3S 282.1290, found 282.1293. The enantiomeric excess
of this isomer was determined by analysis of 1H NMR spectra
of samples containing increasing amounts of the chiral shift
reagent (Eu(hfc)3). syn-isomer: 1H NMR (400 MHz, CDCl3) dH
0.91(s, 9H), 1.59(td, 1H, J ¼ 8.5, 5.7 Hz), 1.94(dt, 1H, J ¼ 7.9,
5.7 Hz), 2.32(s, 3H), 2.68(q, 1H, J ¼ 8.5 Hz), 2.77(td, 1H, J ¼
8.5, 5.7 Hz), 3.66(d, 1H, J ¼ 9.2 Hz), 3.69(d, 1H, J ¼ 9.2 Hz),
7.11(d, 2H, J ¼ 8.0 Hz), 7.27(d, 2H, J ¼ 8.0 Hz). 13C NMR
(100 MHz, CDCl3) dC, 137.0, 130.2, 129.4, 128.7, 78.6, 34.8,
31.5, 25.9, 23.3, 21.1, 10.5. IR (neat) 2959, 1352, 1169, 971, 850.
MS (EI): 282(M1, 3), 131(100). HRMS (EI): calcd for
C15H22O3S 282.1289, found 282.1282. The enantiomeric excess
of this isomer was determined by chiral HPLC analysis (Col-
umn: Daicel OD; Mobile phase: hexane/isopropanol, Reten-
tion time (minutes): 9.96 and 10.7).
2,2-Dimethylpropyl 2-phenylcyclopropanesulfonate. anti-iso-
mer. 1H NMR (400 MHz, CDCl3) dH 0.98(s, 9H), 1.45(dt,
1H, J ¼ 8.5, 6.7 Hz), 1.73(dt, 1H, J ¼ 10.1, 5.3 Hz), 2.59(ddd,
1H, J ¼ 8.5, 5.3, 4.5 Hz), 2.72(ddd, 1H, J ¼ 10.1, 6.7, 4.5 Hz),
3.84(s, 2H), 7.05–7.26(m, 5H). 13C NMR (100 MHz, CDCl3)
dC, 137.1, 128.7, 127.3, 126.5, 79.4, 36.0, 31.7, 26.0, 23.2, 13.6.
IR (neat) 2951, 1344, 1153, 958, 819. MS (EI): 268(M1, 2),
153(6), 117(100). HRMS (EI): calcd for C14H20O3S 268.1133,
found 268.1139. The enantiomeric excess of this isomer was
determined by chiral HPLC analysis (Column: Daicel OD;
Mobile phase: hexane/isopropanol, Retention time (minutes):
7.95 and 8.58) syn-isomer: 1H NMR (400 MHz, CDCl3) dH
0.89(s, 9H), 1.62(td, 1H, J ¼ 8.6, 5.6 Hz), 1.96(dt, 1H, J ¼ 8.0,
5.6 Hz), 2.68(q, 1H, J ¼ 8.6 Hz), 2.82(td, 1H, J ¼ 8.6, 5.6 Hz),
3.70(d, 1H, J ¼ 9.2 Hz), 3.73(d, 1H, J ¼ 9.2 Hz), 7.23–7.38(m,
5H). 13C NMR (100 MHz, CDCl3) dC, 133.3, 129.5, 128.0,
127.3, 78.6, 34.9, 31.5, 25.9, 23.7, 10.5. IR (neat) 2962, 1353,
1168, 969, 839. MS (EI): 268(M1, 2), 181(3), 117(100). HRMS
(EI): calcd for C14H20O3S 268.1133, found 268.1120. The
enantiomeric excess of this isomer was determined by chiral
HPLC analysis (Column: Daicel OD; Mobile phase: hexane/
isopropanol, Retention time (minutes): 7.53 and 8.15).
2,2-Dimethylpropyl 2-(4-chlorophenyl)cyclopropanesulfonate.
anti-isomer. 1H NMR (400 MHz, CDCl3) dH 0.98(s, 9H),
1.50(dt, 1H, J ¼ 8.5, 6.6 Hz), 1.82(dt, 1H, J ¼ 10.0, 5.4 Hz),
2.65(ddd, 1H, J ¼ 8.5, 5.4, 4.5 Hz), 2.76(ddd, 1H, J ¼ 10.0, 6.6,
4.5 Hz), 3.91(s, 2H), 7.06(d, 2H, J ¼ 8.5 Hz), 7.30(d, 2H, J ¼
8.5 Hz). 13C NMR (75 MHz, CDCl3) dC, 135.6, 133.1, 128.9,
127.9, 79.4, 36.1, 31.7, 26.0, 22.6, 13.7. IR (neat) 2959, 1342,
1168, 959, 820. MS (EI): 302(M1, 5), 215(4), 151(100), 115(11).
HRMS (EI): calcd for C14H19O3SCl 302.0743, found 302.0743.
The enantiomeric excess of this isomer was determined by
1
analysis of H NMR spectra of samples containing increasing
1
amounts of the chiral shift reagent (Eu(hfc)3). syn-isomer: H
NMR (300 MHz, CDCl3) dH 0.92(s, 9H), 1.65(td, 1H, J ¼ 8.5,
5.7 Hz), 1.9(dt, 1H, J ¼ 7.9, 5.7 Hz), 2.68(q, 1H, J ¼ 8.5 Hz),
2.82(td, 1H, J ¼ 8.5, 5.7 Hz), 3.70(d, 1H, J ¼ 9.2 Hz), 3.73(d,
1H, J ¼ 9.2 Hz), 7.29(m, 4H). 13C NMR (100 MHz, CDCl3)
dC, 133.3, 131.9, 130.9, 128.2, 78.7, 34.8, 31.6, 26.0, 23.0, 10.7.
IR (neat) 2961, 1355, 1171, 967, 833. MS (EI): 302(M1, 5),
151(100). HRMS (EI): calcd for C14H19O3SCl 302.0743, found
302.0740. The enantiomeric excess of this isomer was deter-
2,2-Dimethylpropyl 2-(2-methoxyphenyl)cyclopropanesulfo-
nate. anti-isomer. 1H NMR (400 MHz, CDCl3) dH 0.99(s,
9H), 1.47(ddd, 1H, J ¼ 8.4, 6.6, 5.5 Hz), 1.76(dt, 1H, J ¼
9.9, 5.5 Hz), 2.59(ddd, 1H, J ¼ 8.4, 5.5, 4.5 HzHz), 2.75(ddd,
1H, J ¼ 9.9, 6.6, 4.5 Hz), 3.79(s, 3H), 3.91(s, 2H), 6.84(d, 2H,
J ¼ 8.6 Hz), 7.06(d, 2H, J ¼ 8.6 Hz). 13C NMR (75 MHz,
CDCl3) dC, 158.9, 129.0, 127.7, 114.1, 79.3, 55.3, 35.9, 31.7,
26.0, 22.7, 13.4. IR (neat) 2965, 1514, 1344, 1238, 1167, 1030,
958, 827. MS (EI): 298(M1, 4), 153(10), 147(100). HRMS (EI):
calcd for C15H22O4S 298.1239, found 298.1234. The enantio-
meric excess of this isomer was determined by chiral HPLC
analysis (Column: Daicel OD; Mobile phase: hexane/isopro-
panol, Retention time (minutes): 11.1 and 12.0) syn-isomer: 1H
NMR (400 MHz, CDCl3) dH 0.91(s, 9H), 1.60(td, 1H, J ¼ 8.5,
5.7 Hz), 1.91(dt, 1H, J ¼ 7.9, 5.7 Hz), 2.66(q, 1H, J ¼ 8.5 Hz),
2.75(td, 1H, J ¼ 8.5, 5.7 Hz), 3.67(d, 1H, J ¼ 9.2 Hz), 3.70(d,
1H, J ¼ 9.2 Hz), 3.77(s, 3H), 6.84(d, 2H, J ¼ 8.8 Hz), 7.30(d,
2H, J ¼ 8.8 Hz). 13C NMR (100 MHz, CDCl3) dC, 158.9,
130.6, 125.3, 113.5, 78.6, 55.2, 34.8, 31.6, 26.0, 23.0, 10.7. IR
(neat) 2960, 1516, 1348, 1246, 1173, 964, 829. MS (EI):
298(M1, 3), 147(100). HRMS (EI): calcd for C15H22O4S
298.1239, found 298.1239. The enantiomeric excess of this
isomer was determined by chiral HPLC analysis (Column:
Daicel OD; Mobile phase: hexane/isopropanol, Retention time
(minutes): 7.37 and 8.95).
1
mined by analysis of H NMR spectra of samples containing
increasing amounts of the chiral shift reagent (Eu(hfc)3).
2,2-Dimethylpropyl 2-(2-nitrophenyl)cyclopropanesulfonate.
anti-isomer. 1H NMR (400 MHz, CDCl3) dH 0.98(s, 9H),
1.62(dt, 1H, J ¼ 8.6, 6.6 Hz), 1.92(dt, 1H, J ¼ 10.0, 5.5 Hz),
2.78(ddd, 1H, J ¼ 8.6, 5.5, 4.5 Hz), 2.90(ddd, 1H, J ¼ 10.0, 6.6,
4.5 Hz), 3.94(s, 2H), 7.50–7.54(m, 2H), 7.97(S, 1H), 8.13(dt,
1H, J ¼ 7.1, 2.2 Hz). 13C NMR (100 MHz, CDCl3) dC, 148.5,
139.4, 133.1, 129.7, 122.3, 121.1, 79.6, 36.3, 31.7, 25.9, 22.6,
14.0. IR (neat) 2965, 1520, 1336, 1167, 964, 833. MS (EI):
313(M1, 1), 298(10), 162(73), 145(11), 116(100). HRMS (EI):
calcd for C14H19O5NS 313.0983, found 313.0985. The enantio-
meric excess of this isomer was determined by chiral HPLC
analysis (Column: Daicel OD; Mobile phase: hexane/isopro-
panol, Retention time (minutes): 9.15 and 11.62) syn-isomer:
1H NMR (400 MHz, CDCl3) dH 0.95(s, 9H), 1.75(td, 1H, J ¼
8.5, 5.6 Hz), 2.03(dt, 1H, J ¼ 8.0, 5.6 Hz), 2.81(q, 1H, J ¼ 8.5
Hz), 2.92(td, 1H, J ¼ 8.5, 5.6 Hz), 3.75(d, 1H, J ¼ 9.2 Hz),
3.78(d, 1H, J ¼ 9.2 Hz), 7.49(t, 1H, J ¼ 8.2 Hz), 7.73(dt, 1H,
J ¼ 8.2, 0.8 Hz), 8.14(dd, 1H, J ¼ 8.2, 2.2 Hz), 8.24(s,1H).
13C NMR (75 MHz, CDCl3) dC, 148.0, 135.8, 135.7, 128.9,
124.7, 122.5, 79.0, 34.8, 31.6, 25.9, 22.9, 10.7. IR (neat) 2953,
1531, 1349, 1172, 955. MS (EI): 313(M1, 6), 298(31), 263(23),
1162
N e w J . C h e m . , 2 0 0 5 , 2 9 , 1 1 5 9 – 1 1 6 3

View Online
2,2-Dimethylpropyl 2,2-diphenylcyclopropanesulfonate. 1H
162(58), 149(26), 116(100). HRMS (EI): calcd for C14H19O5NS
313.0983, found 313.0980. The enantiomeric excess of this
isomer was determined by chiral HPLC analysis (Column:
Daicel OD; Mobile phase: hexane/isopropanol, Retention time
(minutes): 7.5 and 8.7).
NMR (300 MHz, CDCl3) dH 0.96(s, 9H), 1.85(dd, 1H, J ¼
8.7, 5.6 Hz), 2.34(t,1H, J ¼ 5.6 Hz), 3.24(dd, 1H, J ¼ 8.7, 5.6
Hz), 3.79(d, 1H, J ¼ 9.1 Hz), 3.81(d, 1H, J ¼ 9.1 Hz), 7.17–
7.53(m, 10H). 13C NMR (75 MHz, CDCl3) dC, 143.4, 137.7,
129.7, 128.8, 128.3, 127.8, 127.6, 127.2, 79.0, 40.7, 38.7, 31.7,
26.0, 19.0. IR (neat) 2963, 1362, 1167, 970, 837, 702. MS (EI):
176(M1, 1), 192(100), 115(16). HRMS (EI): calcd for
C20H24O3S 344.1446, found 344.1431. The enantiomeric excess
of this isomer was determined by chiral HPLC analysis (Col-
umn: Daicel OD; Mobile phase: hexane/isopropanol, Reten-
tion time (minutes): 7.5 and 8.7).
2,2-Dimethylpropyl 2-(1,1-dimethylethoxy)cyclopropanesulfo-
nate. anti-isomer. 1H NMR (400 MHz, CDCl3) dH 0.99(s, 9H),
1.30(s, 9H), 1.37(ddd, 1H, J ¼ 9.5, 6.7, 4.4 Hz), 1.46(q, 1H, J ¼
6.7 Hz), 2.48(ddd, 1H, J ¼ 9.5, 6.1, 2.3 Hz), 3.80(ddd, 1H, J ¼
9.5, 4.4, 2.3 Hz), 3.88(s, 2H). 13C NMR (75 MHz, CDCl3) dC,
78.8, 76.3, 51.0, 34.3, 31.7, 27.8, 26.0, 13.0. IR (neat) 2973,
1356, 1169, 976, 837. MS (EI): 249(M1 ꢀ Me, 13), 179(26),
127(28), 121(57), 113(100). HRMS (EI): calcd for C11H21O4S
249.1161, found 249.1172. The enantiomeric excess of this
isomer was determined by analysis of 1H NMR spectra of
samples containing increasing amounts of the chiral shift
reagent (Eu(hfc)3). syn-isomer: 1H NMR (400 MHz, CDCl3)
dH 0.99(s, 9H), 1.30(s, 9H), 1.37(dt, 1H, J ¼ 9.3, 6.5 Hz),
1.65(td, 1H, J ¼ 6.5, 5.4 Hz), 2.40(dt, 1H, J ¼ 9.3, 6.5 Hz),
3.58(q, 1H, J ¼ 5.4 Hz), 3.86(d, 1H, J ¼ 9.3 Hz), 3.99(d, 1H,
J ¼ 9.3 Hz). 13C NMR (100 MHz, CDCl3) dC, 79.3, 76.2, 50.7,
33.0, 31.7, 27.8, 26.0, 14.4. IR (neat) 2978, 1369, 1176, 976, 837.
MS (EI): (M1 ꢀ Me, 2), 209(15), 179(54), 153(35), 121(67),
113(100). HRMS (EI): calcd for C11H21O4S 249.1161, found
249.1157. The enantiomeric excess of this isomer was deter-
Acknowledgements
We acknowledge financial support from the Hong Kong
Research Grants Council (Project: HKU 7125/00P) and The
University of Hong Kong. CYZ would like to thank Dr W. Y.
Yu (HKU) for some helpful suggestions.
References
1
(a) M. A. McKervey and T. Ye, J. Chem. Soc., Chem. Commun.,
1992, 823; (b) N. McCarthy, M. A. McKervey, T. Ye, M.
McCann, E. Murphy and M. P. Doyle, Tetrahedron Lett., 1992,
33, 5983; (c) T. Ye, M. A. McKervey, B. D. Brandes and M. P.
Doyle, Tetrahedron Lett., 1994, 35, 7269; (d) T. Ye, C. F. Garcı
and M. A. McKervey, J. Chem. Soc., Perkin Trans. 1, 1995, 1373;
(e) C. F. Garcıa, M. A. McKervey and T. Ye, Chem. Commun.,
1996, 1465.
´
a
1
mined by analysis of H NMR spectra of samples containing
increasing amounts of the chiral shift reagent (Eu(hfc)3).
´
2
(a) M. P. Doyle, M. A. McKervey and T. Ye, Modern Catalytic
Methods for Organic Synthesis with Diazo Compounds; From
Cyclopropanes to Ylides, Wiley, New York, 1998; (b) T. Ye and
M. A. McKervey, Chem. Rev., 1994, 94, 1091; (c) T. Ye, M. A.
McKervey, in The Chemistry of Cyclopropyl Group, ed. Z. Rappo-
port, John Wiley & Sons Ltd., Chichester, 1995, Vol. 2, Ch. 11,
pp. 657–706.
(a) G. Maas, Chem. Soc. Rev., 2004, 33, 183; (b) D. C. Forbes and
M. C. McMills, Curr. Org. Chem., 2001, 5, 1091; (c) M. P. Doyle
and D. C. Forbes, Chem. Rev., 1998, 98, 911.
(a) M. P. Doyle, Q. L. Zhou, C. Charnsangavej, M. A. Longoria,
M. A. McKervey and C. F. Garcia, Tetrahedron Lett., 1996, 4129;
(b) M. P. Doyle, W. R. Winchester, M. N. Protopopova, P.
Muller, G. Bernardinelli, D. Ene and S. Motallebi, Helv. Chim.
Acta, 1993, 76, 2227.
(a) D. A. Evans, K. A. Woerpel, M. M. Hinman and M. M. Faul,
J. Am. Chem. Soc., 1991, 113, 726; (b) R. E. Lowenthal, A. Abiko
and S. Masamune, Tetrahedron Lett., 1990, 31, 6005; (c) H.
Fritschi, U. Leutenegger and A. Pfalz, Helv. Chim. Acta, 1988,
71, 1553.
2,2-Dimethylpropyl 2-(acetyloxy)methylcyclopropanesulfo-
nate. anti-isomer. 1H NMR (400 MHz, CDCl3) dH 1.00(s,
9H), 1.14(dt, 1H, J ¼ 8.4, 6.1 Hz), 1.51(dt, 1H, J ¼ 9.6, 5.6
Hz), 2.00(m, 1H), 2.08(s, 3H), 2.49(dt, 1H, J ¼ 9.6, 6.1 Hz),
3.89(s, 2H), 3.90(dd, 1H, J ¼ 11.8, 7.7 Hz), 4.21(dd, 1H, J ¼
11.8, 5.7 Hz). 13C NMR (75 MHz, CDCl3) dC, 170.6, 79.4,
64.0, 32.0, 31.7, 26.0, 20.7, 18.1, 10.1. IR (neat) 2963, 1744,
1362, 1244, 1173, 1036, 978, 854. MS (EI): 249(M1 ꢀ Me, 5),
209(32), 195(31), 149(10), 113(100). HRMS (EI): calcd for
C10H17SO5 249.0797, found 249.0809. The enantiomeric excess
of this isomer was determined by analysis of 1H NMR spectra
of samples containing increasing amounts of the chiral shift
reagent (Eu(hfc)3). syn-isomer: 1H NMR (400 MHz, CDCl3) dH
1.01(s, 9H), 1.39–1.46(m, 2H), 1.80(q, 1H, J ¼ 8.1 Hz), 2.09(s,
3H), 2.59(td, 1H, J ¼ 8.1, 6.1 Hz), 3.91(d, 1H, J ¼ 9.2 Hz),
3.95(d, 1H, J ¼ 9.2 Hz), 4.34(dd, 1H, J ¼ 11.9, 7.9 Hz),
4.52(dd, 1H, J ¼ 11.9, 7.2 Hz). 13C NMR (100 MHz, CDCl3)
dC, 170.8, 79.2, 61.8, 32.1, 31.7, 26.0, 20.8, 18.3, 11.0. IR (neat)
3
4
5
6
M. Endo, M. Sasako, K. Ogawa, Y. Tani and H. Tomioka, Jpn.
Kokai Tokkyo Koho, 1989, JP 01033543 A2.
A. Berkessel and M. Voges, Chem. Ber., 1989, 122, 1147.
R. L. Danheiser, R. F. Miller, R. G. Brisbois and S. Z. Park,
J. Org. Chem., 1990, 55, 1959.
2961, 1744, 1354, 1233, 1167, 1034, 968. MS (EI): 249(M1
ꢀ
7
8
Me, 2), 209(28), 195(32), 149(12), 113(100). HRMS (EI): calcd
for C10H17SO5 249.0797, found 29.0795.
9
Anti/syn ratio was determined by 1 H NMR analysis of crude
reaction mixture.
2,4-Dimethyl-3-pentyl
2-(2-nitrophenyl)cyclopropanesulfo-
10 (a) M. P. Doyle, W. R. Winchester, J. A. A. Hoorn, V. Lynch, S.
H. Simonsen and R. Ghosh, J. Am. Chem. Soc., 1993, 115, 9968;
(b) M. P. Doyle, Aldrichimica Acta, 1996, 29, 3.
11 M. Kennedy, M. A. Mckervey, A. R. Maguire and G. H. P. Roos,
J. Chem. Soc., Chem. Commun., 1990, 361.
nate. anti-isomer. 1H NMR (400 MHz, CDCl3) dH 1.00(m,
12H), 1.58(ddd, 1H, J ¼ 8.5, 6.5, 5.4 Hz), 1.91(dt, 1H, J ¼ 10.8,
5.4 Hz), 2.04(m, 2H), 2.79(dt, 1H, J ¼ 8.5, 5.4 Hz), 2.89(ddd,
1H, J ¼ 10.8, 6.5, 4.5 Hz), 4.40(t, 1H, J ¼ 5.7 Hz), 7.48–7.54(m,
2H), 7.97(s, 1H), 8.12(dt, 1H, J ¼ 7.0, 2.1 Hz). 13C NMR (100
MHz, CDCl3) dC, 148.4, 139.8, 133.1, 129.7, 122.2, 121.1, 95.2,
37.9, 30.15, 30.11, 23.0, 20.00, 19.98, 17.78, 17.6, 14.5. IR
(neat) 2970, 1536, 1351, 1167, 892. MS (EI): 341(M1, 3),
298(100), 162(51), 116(48). HRMS (EI): calcd for C16H23NSO5
341.1296, found 341.1287. The enantiomeric excess of this
isomer was determined by chiral HPLC analysis (Column:
Daicel OD; Mobile phase: hexane/isopropanol, Retention time
(minutes): 9.5 and 11.2).
12 N. Watanabe, T. Ogawa, Y. Ohtake, S. Ikegami and S.-I. Ha-
shimoto, Synlett., 1996, 85.
13 Ligands d were prepared by mono-protection of (S)-4,40,5,50,6,60-
hexamethoxy-2,20-diphenic acid, which in turn, was prepared
according to a published procedure. For details, see: T. Itoh, J.
Chika, S. Shirakami, H. Ito, T. Yoshida, Y. Kubo and J. Uenishi,
J. Org. Chem., 1996, 61, 3700.
14 The ee value was determined either by chiral HPLC on a chiralcel
OD column or analysis of 1H NMR spectra of samples containing
increasing amounts of the chiral shift reagent Eu(hfc)3. For details,
please refer to the experimental section.
N e w J . C h e m . , 2 0 0 5 , 2 9 , 1 1 5 9 – 1 1 6 3
1163