Benaglia et al.
ene); H NMR δ 7.67 (d, 2H, J ) 3.77 Hz), 7.09 (d, 2H, J )
1
rate of some powers of ten. An opposite, but equally
relevant, effect was found in some palladium-mediated
carbon-carbon bond-forming reactions, where medium-
rich diphosphines appear to give much more active
complexes than the electron-rich ones.24
Even though the comparison of the catalytic perfor-
mances of the complexes of structurally different ligands
is questionable, it is worth comparing the behavior of the
biaryl-based with Evans-type bis(oxazolines). It is inter-
esting to note how ligands endowed with similar elec-
tronic properties display completely different catalytic
activities, further suggesting that the electronic proper-
ties do not play a decisive role.
3
.77 Hz), 5.97 and 5.95 (broad d, 2 NH), 3.88 (m, 2H), 3.75
dd, 2H, J ) 11.5 Hz and J ) 3.42 Hz), 3.32 (dd, 2H, J
1.5 Hz and J ) 7.34 Hz), 2.52 (broad s, 2H), 0.71 (s, 18H);
C NMR 27.0, 33.7, 59.9, 62.6, 130.5, 131.4, 134.3, 138.7,
(
1
2
1
)
1
2
1
3
1
32 2 4 2
62.0; MW 452.63 Da. Anal. Calcd for C22H N O S : C, 58.38;
H, 7.13; N, 6.19. Found: C, 58.10; H, 7.11; N, 6.35.
4,4′-Bis[N-(1′S)-(1′-tert-butyl-2′-hydroxyethyl)carbox-
amido]-3,3′-bithiophene (7b): yield 70%; mp 145 °C (tritu-
1
rated with diethyl ether); H NMR δ 8.26 (d, 2H, J ) 3.5 Hz),
7
2
2
.44 (d, 2H, J ) 3.5 Hz), 5.75 and 5.77 (broad d, 2H), 3.85 (m,
H), 3.74 (dd, 2H, J
1
) 11.7 Hz and J
2
) 3.07 Hz), 3.32 (dd,
H, J ) 11.7 Hz and J
1
2
) 6.56 Hz), 2.52 (broad s, 2 H), 0.75
13
(
s, 18H); C NMR 26.0, 32.8, 60.9, 66.6, 131.5, 132.4, 135.3,
1
32 2 4 2
40.0, 162.0; MW 452.63 Da. Anal. Calcd for C22H N O S :
Recent theoretical studies25 have demonstrated that
the copper(I)-mediated cyclopropanation proceeds via a
metal-carbene complex, formed by association of the
diazo compound to the catalyst with concomitant extru-
sion of nitrogen. The formation of the copper-carbene
intermediate is the rate-determining step,26 while the
direct carbene insertion into the double bond, which leads
to the different isomeric cyclopropanes and which is
responsible of the stereochemical outcome of the reaction,
occurs after this step. Although special care must be
taken in order to compare theoretical studies with real
C, 58.38; H, 7.13; N, 6.19. Found: C, 58.20; H, 7.21; N, 6.25.
4,4′-Bis[N-(1′S)-(1′-phenyl-2′-hydroxyethyl)carbox-
amido]-3,3′-bithiophene (7c): yield 76%; mp 135-138 °C
1
(
triturated with diethyl ether); H NMR δ 8.15 (d, 2H, J )
3
6
1
.44 Hz), 7.39 (d, 2H, J ) 3.44 Hz), 7.25 (m, 6H), 7.04 (m, 4H),
.36 and 6.33 (broad d, 2H), 5.07 (m, 2H), 3.89 (dd, 2H, J
1.66 Hz and J ) 3.51 Hz), 3.64 (dd, 2H, J ) 11.66 Hz and
) 5.65 Hz), 3.25 (broad s, 2H), 0.75 (s, 18H); MW 492.61
Da. Anal. Calcd for C26 : C, 63.39; H, 4.91; N, 5.69.
Found: C, 63.19; H, 4.88; N, 5.72.
1
)
2
1
J
2
24 2 4 2
H N O S
2,2′,5,5′-Tetramethyl-4,4′-bis[N-(1′S)-(1′-tert-butyl-2′-hy-
droxyethyl)carboxamido]-3,3′-bithiophene (7d) and (7e).
2
7
2
Column chromatography (SiO , eluant hexane/AcOEt 1:1). The
cases, it is worth mentioning that density functional
theory (DFT) calculations have shown that steric interac-
tions between the ester group of the diazo compound and
substituents on the bis(oxazoline) and the geometry of
chelate ligand-Cu complex are responsible for the enan-
2
5
first product eluted was 7d: yield 32%; mp 219 °C; [R]
D
)
1
-
26 (c ) 1, CHCl
.82 (m, 2H), 3.72 (dd, 2H, J
.57 (dd, 2H, J ) 11.2 Hz and J
.12 (s, 6H), 1.95 (broad s, 2H), 0.87 (s, 18H); C NMR 13.7,
3
); H NMR δ 6.75 and 6.72 (broad d, 2H),
) 11.2 Hz and J ) 3.33 Hz),
) 8.12 Hz), 2.52 (s, 6H),
3
3
2
1
2
1
2
13
28
tio- and diastereoselectivity of the process. These recent
findings support the results of the present research,
where steric factors and catalyst geometrical features
14.6, 27.3, 33.7, 60.1, 63.6, 131.5, 134.9, 135.6, 137.2, 167.8;
MW 508.71 Da. Anal. Calcd for C26
H
40
N
2
O
4
S
2
: C, 61.38; H,
7
.93; N, 5.51. Found: C, 61.10; H, 7.81; N, 5.35.
The second product eluted was 7e: yield 32%; mp 195 °C;
clearly overwhelm any consideration of the electronic
2
5
1
properties of the chiral ligands.29
[R]
D
) -8 (c ) 0.54, CHCl
3
); H NMR δ 6.00 (broad s, 2H),
) 11.7 Hz and J ) 3.06 Hz),
) 11.7 Hz and J ) 6.52 Hz), 2.65 (s, 6H),
.25 (broad s, 2H), 2.20 (s, 6H), 0.87 (s, 18H); C NMR 13.3,
3
3
2
.82 (m, 2H), 3.73 (dd, 2H, J
.57 (dd, 2H, J
1
2
In this work, the electrochemical oxidative potential
was employed for the first time the as a tool to quanti-
tatively evaluate the electronic availability of the nitro-
gen function in oxazolines, a parameter which was found
to be very useful and reliable in the case of phosphorus
ligands.
1
2
13
15.2, 26.7, 33.4, 59.3, 62.4, 130.7, 132.4, 134.0, 142.4, 165.4;
MW 508.71 Da. Anal. Calcd for C26
40 2 4 2
H N O S : C, 61.38; H,
7.93; N, 5.51. Found: C, 61.20; H, 7.83; N, 5.55.
General Procedure for the Synthesis of the Bisoxazo-
lines 2, 3a, 3b, 4a, and 4b. The Burgess reagent (methyl
N-{[(triethylammonio)sulfonyl]carbamate) (2 mmol) was added
to a solution of the dicarboxamide (1 mmol) in THF. The
reaction mixture was stirred for 24-72 h. The white precipi-
Experimental Section
General Procedure for the Synthesis of the Dicar-
tate was filtered off and the residue filtered over SiO
2
pad to
boxamides 7a-e. A solution of the dicarboxylic acid dichlo-
give the bisoxazoline derivative in a pure state.
2 2
ride (1 mmol) in dry CH Cl was dropped, under nitrogen, at
2
,2′-Bis[(S)-4,5-dihydro-4-(1,1-dimethylethyl)oxazol-2-
0
°C into a stirred solution of TEA (2 mmol) and (S)-tert-
yl]-3,3′-bithiophene (2): reaction time 72 h; filtered over a
leucinol or (S)-phenylglycinol (2 mmol) in dry CH Cl . The
2
2
1
SiO
2 2 2
pad with CH Cl /AcOEt 9:1 as eluant; yield 80%; H NMR
reaction mixture was stirred at rt for 1 night and then washed
with 1 N HCl and then with water. The organic layer was
δ 7.33 (d, 2H, J ) 5.11 Hz), 7.02 (d, 2H, J ) 5.11 Hz), 4.07 (m,
1
3
4
2
4
H), 3.87 (dd, 2H, J
6.2, 34.4, 69.4, 77.1, 127.0, 131.5, 131.1, 138.6, 159.4; MW
16.60 Da. Anal. Calcd for C22 : C, 63.43; H, 6.77;
1 2
) 10.2 Hz and J ) 6.9 Hz); C NMR
2 4
separated and dried (Na SO ) and the solvent removed under
reduced pressure to afford crude compounds 7a-e which were
28 2 2 2
H N O S
purified by crystallization or chromatography.
N, 6.72. Found: C, 63.90; H, 6.81; N, 6.75.
,4′-Bis[(S)-4,5-dihydro-4-(1,1-dimethylethyl)oxazol-2-
yl]-3,3′-bithiophene (3a): reaction time 24 h; filtered over
2
,2′-Bis[N-(1′S)-(1′-tert-butyl-2′-hydroxyethyl)carbox-
4
amido]-3,3′-bithiophene (7a): yield 90%; mp 206 °C (tolu-
1
SiO
2 2 2
pad with CH Cl /AcOEt 9:1 as eluant; yield 80%; H NMR
(
24) Tietze, L. F.; Thede, K.; Schimpf, R.; Sannicol o` , F. J. Chem.
δ 7.87 (d, 2H, J ) 3.39 Hz), 7.18 (d, 2H, J ) 3.39 Hz), 4.07
Soc., Chem. Commun. 1999, 1811-1812. Tietze, L. F.; Thede, K.;
Sannicol o` , F. J. Chem. Soc., Chem. Commun. 2000, 583-584.
13
(
dd, 2H, J
1
) 9.9 Hz and J
6.6, 36.5, 67.1, 75.1, 127.6, 130.0, 131.9, 139.0, 161.1; MW
16.60 Da. Anal. Calcd for C22 : C, 63.43; H, 6.77;
2
) 8.1 Hz), 3.86 (m, 4H); C NMR
2
4
(
25) Fraile, J. M.; Garcia, J. I.; Martinez-Merino, V.; Mayoral, J.
28 2 2 2
H N O S
A.; Salvatella, L. J. Am. Chem. Soc. 2001, 123, 7616-7625.
26) Salomon, R. G.; Kochi, J. K. J. Am. Chem. Soc. 1973, 95, 3300-
310.
27) Cornejo, A., Fraile, J. M., Garcia, J. L., Gil, M. J., Martinez-
Merino, V., Mayoral, J. A., Salvatella, L. Angew. Chem., Int. Ed. 2005,
4, 458-461.
28) Fraile, J. M.; Garcia, J. I.; Gil, M. J.; Martinez-Merino, V.;
Mayoral, J. A.; Salvatella, L. Chem. Eur. J. 2004, 10, 758-765.
(
N, 6.72. Found: C, 68.10; H, 6.71; N, 6.55.
,4′-Bis[(S)-4,5-dihydro-4-(phenyl)oxazol-2-yl]-3,3′-
bithiophene (3b): reaction time 24 h; filtered over SiO pad
) -3.6 (c
); mp 122 °C; H NMR δ 8.04 (d, 2H, J ) 3.4 Hz),
7.21 (m, 12H), 5.18 (dd, 2H, J ) 9.8 Hz and J ) 8.77 Hz),
3
4
(
2
2
5
with hexane/AcOEt 8:2 as eluant; yield 80%; [R]
) 1, CHCl
3
D
4
1
(
1
2
7494 J. Org. Chem., Vol. 70, No. 19, 2005