J = 6.7 Hz), 1.68 (6H, s), 2.15 (3H, s), 2.97 (1H, septet, J =
6.7 Hz), 6.62 (2H, s), 7.21 (2H, dt, J = 7.6, 1.1 Hz), 7.38 (2H,
dt, J = 7.6, 1.1 Hz), 7.44 (2H, d, J = 7.6 Hz), 7.77 (2H, d,
J = 7.6 Hz). 13C-NMR (CD3CN, 150.8 MHz, 25 ◦C) d 17.9
(2CH3), 18.9 (2CH3), 20.1 (CH3), 36.5 (CH), 72.7 (Cq), 119.7
(2CH), 126.5 (2CH), 127.2 (2CH), 128.0 (2CH), 128.2 (2CH),
133.1 (CH), 138.0 (2Cq), 139.7 (Cq), 141.7 (2Cq), 144.7 (2Cq),
210.5 (Cq). HRMS (EI) calculated for C26H26O: 354.1984; found
354.1982.
showed a single imaginary frequency. Visual inspection of the
corresponding normal mode was used to confirm that the right
transition state had been found. NMR chemical shift calculations
were obtained with the GIAO34 method at the B3LYP/6-
311++G(2d,p)//B3LYP/6-31G(d) level. TMS, calculated at the
same level of theory, was used as reference to scale the absolute
shielding value.
Acknowledgements
L.L. and A.M. received financial support from the University of
Bologna (RFO) and from MUR-COFIN 2005, Rome (national
project “Stereoselection in Organic Synthesis”). The authors
thanks one anonymous referee for helpful suggestions.
NMR spectroscopy
1
The spectra were recorded at 600 MHz for H and 150.8 MHz
for 13C on a Varian Inova spectrometer. Low temperature spectra
were obtained with a customized dual band direct probe. The
assignments of the 1H and 13C signals were obtained by bi-
dimensional experiments (edited-gsHSQC28 and gsHMBC29). The
NOE experiments were obtained by means of the DPFGSE-
NOE30 sequence. To selectively irradiate the desired signal, a
50 Hz wide shaped pulse was calculated with a refocusing-SNOB
shape31 and a pulse width of 37 ms. The mixing time was set to
1.0 s. The samples for obtaining spectra at temperatures lower
than -100 ◦C were prepared by connecting to a vacuum line
the NMR tubes containing the compound and some C6D6 for
locking purposes and condensing therein the gaseous CHF2Cl
and CHFCl2 (4 : 1 v/v) under cooling with liquid nitrogen. The
tubes were subsequently sealed in vacuo and introduced into the
cooled probe of the spectrometer. Temperature calibrations were
performed before the experiments, using a Cu/Ni thermocouple
immersed in a dummy sample tube filled with isopentane, and
under conditions as nearly identical as possible. The uncertainty
in the temperatures was estimated from the calibration curve to
References and notes
1 M. Oki, Applications of Dynamic NMR Spectroscopy to Organic
Chemistry, VCH Publishers, Deerfield Beach, FL, 1985, p. 211.
2 A. Nishida, M. Takeshita, S. Fujisaki and S. Kajigaeshi, Bull. Soc.
Chim. Jpn., 1988, 61, 1195–1200.
3 A. Nishida, Y. Akagawa, S. Shirakawa, S. Fujisaki and S. Kajigaeshi,
Can. J. Chem., 1991, 69, 615–619.
4 J. Vicario, A. Meetsma and B. L. Feringa, Chem. Commun., 2005, 5910–
5012; J. Vicario, M. Walko, A. Meetsma and B. L. Feringa, J. Am. Chem.
Soc., 2006, 128, 5127–51235.
5 (a) D. Casarini, L. Lunazzi and A. Mazzanti, J. Org. Chem., 2008, 73,
2811–2818; (b) D. Casarini, L. Lunazzi and A. Mazzanti, J. Org. Chem.,
2008, 73, 6382–6385.
6 MMFF conformational search implemented in TITAN 1.0.5, Wavefunc-
tion Inc, Irvine, CA.
7 MMX force field as in the program PC-Model V. 7.5, Serena Software,
Bloomington, IN.
8 M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb,
J. R. Cheeseman, J. A. Montgomery, Jr., T. Vreven, K. N. Kudin, J. C.
Burant, J. M. Millam, S. S. Iyengar, J. Tomasi, V. Barone, B. Mennucci,
M. Cossi, G. Scalmani, N. Rega, G. A. Petersson, H. Nakatsuji, M.
Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T.
Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J. E.
Knox, H. P. Hratchian, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo,
R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi,
C. Pomelli, J. Ochterski, P. Y. Ayala, K. Morokuma, G. A. Voth, P.
Salvador, J. J. Dannenberg, V. G. Zakrzewski, S. Dapprich, A. D.
Daniels, M. C. Strain, O. Farkas, D. K. Malick, A. D. Rabuck, K.
Raghavachari, J. B. Foresman, J. V. Ortiz, Q. Cui, A. G. Baboul, S.
Clifford, J. Cioslowski, B. B. Stefanov, G. Liu, A. Liashenko, P. Piskorz,
I. Komaromi, R. L. Martin, D. J. Fox, T. Keith, M. A. Al-Laham, C. Y.
Peng, A. Nanayakkara, M. Challacombe, P. M. W. Gill, B. G. Johnson,
W. Chen, M. W. Wong, C. Gonzalez and J. A. Pople, GAUSSIAN 03
(Revision E.01), Gaussian, Inc., Wallingford, CT, 2004.
be
2
◦C. Low temperature 13C spectra were acquired without
spinning, with a sweep width of 38000 Hz, a pulse width of 4.9 ms
(70◦ tip angle), and a delay time of 2.0 s. Proton decoupling was
achieved with the standard Waltz-16 sequence. A line broadening
function of 1–5 Hz was applied to the FIDs before Fourier
transformation. Usually 512 to 1024 scans were acquired. The
line shape simulations were performed by means of a PC version
of the QCPE program DNMR 6 no. 633, Indiana University,
Bloomington, IN.
Computational details
9 The average distances used for the comparison with the NOE effects
were derived from the DFT-computed structures by means of the
relationship ꢀr-6ꢁ-1/6, according to: T. D. W. Claridge, High-Resolution
NMR Techniques in Organic Chemistry, Pergamon, Oxford, 1987, p.
Geometry optimizations were usually carried out at the B3LYP/6-
31G(d) level by means of the Gaussian 03 series of programs8
and XeonTM multiprocessor servers running Scientific Linux
5.2-X86_64 as the operating system. In the case of 1, full
geometry optimization was carried out also at the B3LYP/6-
311++G(2d,p)32, PBE1PBE/6-31G(d)33, M05–2X/6-31G(d)13h
RHF(full)/6-31G(d) and RHF/cc-pVDZ levels of theory. Single-
point calculations were obtained at the MP2(full)/6-31G(d)//
˚
303. In 1-anti these distances are 3.07 A (between H-9 and H-1,8) and
˚
2.25 A (between H-9 and Hortho). In 1-syn the same distances are 3.07
and 4.08 A, respectively. Their ratios (elevated to the 6th power) are
˚
6.4 : 1 in 1-anti whereas they are reversed to 1 : 5.5 in 1-syn.
10 The 94 : 6 ratio measured at -147 ◦C (Fig. 1) corresponds, approx-
imately, to a 86 : 14 ratio at -80 ◦C. Therefore, the observed NOE
effects at -80 ◦C are mainly due to the geometry of the more populated
conformer. However, the presence of a non-negligible amount of
the minor conformer should account for the difference between the
calculated NOE ratio for a 100% population of 1-anti (i.e. 6.4 : 1) and
the experimental value (i.e. 3.1 : 1). In particular, the observed 3.1 NOE
ratio would be accounted for by an anti-to-syn proportion of 73 : 27:
such a proportion is in acceptable agreement with the above mentioned
86 : 14 ratio.
,
B3LYP/6-311++G(2d,p)
and
CISD/6-31G(d)//B3LYP/6-
311++G(2d,p). The standard Berny algorithm in redundant
internal coordinates and default criteria of convergence
were employed in all the calculations. Harmonic vibrational
frequencies were calculated for all the optimized stationary
points, For each ground state the frequency analysis showed the
absence of imaginary frequencies, whereas each transition state
11 Assignment unambiguously established by means of NOE experiments
obtained by irradiation of isopropyl CH and methyl signals.
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The Royal Society of Chemistry 2009
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