Temperature-independent stereocontrolled [2+2] cycloaddition. Potential of the 2,4-pentanediol tether in asymmetric reactions as a differential activation entropy promoter

Full text of DOI:10.1021/ja993976o

2128
J. Am. Chem. Soc. 2000, 122, 2128-2129
stereocontrol. Thus, we assume that the chiral fate of the reaction
is prearranged in the ground state.
Temperature-Independent Stereocontrolled [2+2]
Cycloaddition. Potential of the 2,4-Pentanediol
Tether in Asymmetric Reactions as a Differential
Activation Entropy Promoter
In this communication, we report that a PD-tethered [2+2]
cycloaddition of an olefin and a ketene could perform strict
diastereodifferentiation in the temperature range as wide as 195-
423 K. Similar tethers having a single chiral center showed varied
diastereodifferentiating abilities, which had almost no temperature
dependencies in the same wide range. The present results suggest
the potential of the PD tether to induce sufficient differential
activation entropy and reveal a new aspect for designing asym-
metric reactions.
Takashi Sugimura,* Takahiro Tei, Atsushi Mori,
Tadashi Okuyama, and Akira Tai
Faculty of Science, Himeji Institute of Technology
Kohto, Kamigori, Ako-gun, Hyogo 678-1297, Japan
The Eyring treatment5 of the reaction rates of independent
parallel processes to give respective stereoisomers in asymmetric
reaction provides a differential activation enthalpy (∆∆Hq) and
entropy (∆∆Sq) as shown in eq 1.6 Most known asymmetric
ReceiVed NoVember 11, 1999
We have been studying asymmetric reactions using optically
active 2,4-pentanediol (PD)1 as a chiral tether between a prochiral
reactant and a reagent.2 A variety of reactant-reagent combina-
tions have resulted in high diastereodifferentiation to give products
easily with over 99% diastereomeric excess (de) without detailed
optimization of the reaction conditions, and after the reaction,
the tether part can be removed from the product without
epimerization. The excellent ability and the wide applicability of
reactions have been designed to induce sufficient ∆∆Hq by steric
repulsion, structural strain, or electronic interaction in the transi-
tion states. As a result, these reactions have a temperature-
dependence of stereodifferentiation and are performed at low
temperatures so that the reactions can proceed with better
stereocontrol although the temperature must also be high enough
to achieve a practical rate of reaction. An entropy-controlled
asymmetric reaction having sufficient ∆∆Sq is preferable from a
synthetic viewpoint. Reactions of varied reagent-reactant com-
binations can then be performed to keep the stereocontrol high
enough, independent of the reaction temperature, and thus,
optimization for each reaction system is not necessary.
To investigate the potential of PD-tethered reactions which may
have sufficient ∆∆Sq, the diastereodifferentiating ability over a
wide range of temperatures should be studied to minimize the
uncertainties due to the extrapolation of the experimental data to
1/T (K-1) ) 0. In this context, the thermal [2+2] cycloaddition
of an olefin with a ketene was selected, since the addition is rapid
and a ketene can be readily generated by a photochemical method
fromadiazocarbonylcompoundthroughtheWolffrearrangement.7-9
The substrate 1a was prepared from (2R,4R)-PD by the reported
method,2e and photolyzed in pentane (e293 K) or decane (g296
K) solution with a low-pressure mercury lamp in a temperature
range of 195-423 K (by 10-23 K steps). The majority of the
carbene generated by photoirradiation was trapped by the solvent,
but the expected [2+2] cycloadduct was also produced (10-33%
isolated yield).10-12 At all temperatures, the adduct was the
the PD-tethered reaction is thus established as a handy stereo-
controller for asymmetric reactions.3,4 However, the stereocontrol
mechanisms for these reactions were not readily comprehensible.
The chiral tether part has only two small methyl groups and leads
to a flexible medium ring (8- to 10-membered ring) in the
transition states, where the methyl groups are not expected to
cause enough steric repulsion nor structural strain to perform strict
(1) (a) Tai, A.; Kikukawa, T.; Sugimura, T.; Inoue, Y.; Abe, S.; Osawa,
T.; Harada, T. Bull. Chem. Soc. Jpn. 1994, 67, 2473-77. (b) Kitamura, M.;
Ohkuma, T.; Inoue, S.; Sayo, N.; Kumobayashi, H.; Akutagawa, S.; Ohota,
T.; Takaya, H.; Noyori, R. J. Am. Chem. Soc. 1988, 110, 629-631. Kawano,
H.; Ishii, Y.; Saburi, M.; Uchida, Y. J. Chem. Soc., Chem. Commun. 1988,
87-88.
(2) (a) Sugimura, T.; Futagawa, T.; Tai, A. Tetrahedron Lett. 1988, 29,
5775-79. Sugimura, T.; Futagawa, T.; Yoshikawa, M.; Tai, A. Tetrahedron
Lett. 1989, 30, 3807-10. Sugimura, T.; Yoshikawa, M.; Futagawa, T.; Tai,
A. Tetrahedron 1990, 46, 5955-66. Sugimura, T.; Yoshikawa, M.; Mizuguchi,
M.; Tai, A. Chem. Lett. 1999, 831-832. (b) Underiner, T. L.; Paquette, L. A.
J. Org. Chem. 1992, 57, 5438-46. Sugimura, T.; Nishiyama, N.; Tai, A.;
Hakushi, T. Tetrahedron: Asymmetry 1994, 5, 1163-66. Sugimura, T.; Iguchi,
H.; Tsuchida, R.; Tai, A.; Nishiyama, N.; Hakushi, T. Tetrahedron: Asymmetry
1998, 9, 1007-13. (c) Sugimura, T.; Nishiyama, N.; Tai, A. Tetrahedron:
Asymmetry 1993, 4, 43-44. (d) Sugimura, T.; Yamada, H.; Inoue, S.; Tai, A.
Tetrahedron: Asymmetry 1997, 8, 649-655. Sugimura, T.; Inoue, S.; Tai,
A. Tetrahedron Lett. 1998, 39, 6487-6490. (e) Mori, A.; Sugimura, T.; Tai,
A. Tetrahedron: Asymmetry 1997, 8, 661-664. (f) Sugimura, T.; Nagano,
S.; Tai, A. Chem. Lett. 1998, 45-46. (g) Yamaguchi, K.; Sugimura, T.;
Nishida, F.; Tai, A. Tetrahedron Lett. 1998, 39, 4521-24.
(3) Since the latest mechanistic study of the Lewis acid promoted
diastereodifferentiating nucleophilic addition to a PD acetal suggested an SN1-
like mechanism, some of the reactions of PD acetals might also be classified
into the group of PD tethered reactions. Sammakia, T.; Smith, R. S. J. Am.
Chem. Soc. 1992, 114, 10998-10999.
(4) For examples of the reactions using other bifunctional chiral auxiliaries
as tethers, see: (a) Green, B. S.; Rabinsohn, Y.; Rejto, M. J. Chem. Soc.,
Chem. Commun. 1975, 313-314. (b) Ukaji, Y.; Sada, K.; Inomata, K. Chem.
Lett. 1993, 1227-1230. (c) Lipshutz, B. L.; Liu, Z.; Kayser, F. Tetrahedron
Lett. 1994, 35, 5567-5570. (d) Lipshutz, B. H.; Kayser, F.; Liu, Z. Angew.
Chem., Int. Ed. Engl. 1994, 33, 1842-1844. (e) Lipshutz, B. H.; James, B.;
Vance, S.; Carrico, I. Tetrahedron Lett. 1997, 38, 753-756. (f) Koide, N.;
Hattori, T.; Miyano, S. Tetrahedron: Asymmetry 1994, 5, 1899-1994.
(5) Eyring, H. J. Chem. Phys. 1935, 3, 107-115.
(6) (a) Eliel, E. L. StereoselectiVity of Carbon Compounds; MacGraw-
Hill: New York, 1962; pp 151-152, 237-239. (b) Seyden-Penne, J. Chiral
Auxiliaries and Ligands in Asymmetric Synthesis; Wiley: New York, 1995;
pp 1-6. (c) Nogradi, M. StereoselectiVe Synthesis; VHC: Weinheim, 1995;
pp 41-43. (d) Gawley, R. E. Principles of Asymmetric Synthesis; Pergamon:
Oxford, 1996; pp 7-10.
(7) For a review of [2+2] cycloaddition of ketenes, see: Hyatt, J. A.;
Raynolds, P. W. Org. React. 1994, 45, 159-646.
(8) For diastereodifferentiating [2+2] addition of ketene to olefin, see: (a)
Granz, I.; Kunz, H. Synthesis 1994, 1353-58. (b) Kanazawa, A.; Delair, P.;
Pourashraf, M.; Greene, A. E. J. Chem. Soc., Perkin Trans. 1 1997, 1911-
21. (c) Cagnon, J. R.; Bideau, F. L.; Marchand-Brynaert, J.; Ghosez, L.
Tetrahedron Lett. 1997, 38, 2291-2294.
(9) For reviews of the Wolff rearrangement, see: (a) Meier, H.; Zeller, K.
P.; Angew. Chem. 1975, 87, 52-61. (b) Gill, G. B. In ComprehensiVe Organic
Synthesis; Trost, B. M., Ed.: Pergamon: Oxford, 1991; Vol. 3, pp 887-912.
(10) The stereochemical purities were determined by GLC equipped with
FID or MS. Four more isomeric adducts, 1,2-trans-adducts and 2-keto-adducts,
are possible besides 3. Analyses of the reaction mixtures and those after
solvolysis indicated that formation of the isomers of 2 is below the detection
limit (<0.5%) except for 3d and 3c. The de and isolated yield of 2 (and 3)
were somewhat affected by the solvent used, photoirradiation time, and the
irradiation wavelength. See the Supporting Information for the details.
10.1021/ja993976o CCC: $19.00 © 2000 American Chemical Society
Published on Web 02/18/2000

Communications to the Editor
J. Am. Chem. Soc., Vol. 122, No. 9, 2000 2129
Scheme 2
Figure 1. Plots of ln(k2/k3) as a function of 1/T for the reactions of 1c
(O) and 1d (b). The abscissa is extended to T ) ∞ to show the intercepts.
Differential activation parameters are ∆∆Hq ) 0.23 ( 0.05 kcal mol-1
and ∆∆Sq ) 6.00 ( 0.02 cal mol-1 K-1 for 1c and ∆∆Hq ) -0.03 (
0.01 kcal mol-1 and ∆∆Sq ) 0.26 ( 0.04 cal mol-1 K-1 for 1d.
Since the direction controlled by the methyl chiralities in 1b
and 1c was the same as that of 1a, the two methyl groups in 1a
can be considered to work cooperatively to differentiate the
diastereoface. On the contrary, the two methyl groups of 1e were
expected to compete with each other in the stereocontrol due to
the entropy factors. When 1e was photolyzed in the same
temperature range, the [2+2] addition was sluggish and the
adducts were not observed (<3%). The two methyl groups must
interfere with the attacks on the respective stereofaces to retard
the [2+2] addition itself independent of temperature.
Scheme 1
In the present study, the PD-tethered [2+2] addition was proven
to have rigorous diastereodifferentiation (>99% de) over a wide
range of temperature, and the reason for the stereocontrol was
shown to be the differential activation entropy, ∆∆Sq. The
effective induction of ∆∆Sq with the PD tether can be explained
as follows. Formation of a medium ring from a flexible substrate
requires a great loss of entropy, the degree of which largely
depends on the conformational property of the substrate.14 The
PD-tethered reaction starts with the encounter of the reagent and
reactant moieties, and the accompanying large entropy loss would
result in enough difference in entropy between the two diaster-
eomeric encounter states from the influence of the chiralities on
the tether. This difference is carried over to the transition states
to give ∆∆Sq.6,15 The differentiated face of the olefin in 1a was
si,re as was the case for the metal-catalyzed carbenoid addition
of 1a2e and other related reactions.2a,b Thus, all the PD-tethered
reactions might also have a large enough ∆∆Sq and be stereo-
controlled by the differential activation entropy. This prediction
is very compatible with the fact that the stereocontrol ability of
PD tether does not depend on the reaction types or rates. The
success of the PD tethered reaction as a versatile stereocontroller
indicates that an entropy-controlled asymmetric reaction can
perform high stereodifferentiation with a much simpler reaction
design than the conventional asymmetric reactions of enthalpy
control, and provides a new principle for the design of asymmetric
reactions.
(1R,6R)-isomer 2a and none of the diastereomer 3a was detected
(<0.5% of 2a). Thus, the stereocontrol with the PD tether was
shown to be rigorous between the temperature of 195 and 423
K. The ratio of k2/k3 > 200 (> 99% de) at 423 K translates to
∆∆Gq > 4.4 kcal mol-1, the origin of which is difficult to explain
with only ∆∆Hq for such a rapid reaction.
The stereocontrol ability of each chirality on the PD tether was
examined using substrates 1b-d (racemic mixtures) having a
methyl group at different positions on the tether moiety. Photolysis
of 1b again yielded a single diastereomer of 2b from 195 to 400
K (4-14% isolated yield). In the cases of 1c and 1d, a mixture
of 2 and 3 was obtained (4-16% and 3-8% isolated yields,
respectively). The de values of 2c only varied from 84% to 88%,
and those for 2d (or 3d) varied from 10% to 11%. That is, the
ratios of diastereomers 2/3 in the reactions of 1c and 1d were
almost unchanged in the temperature range twice as wide as in
Kelvin. Plots of the ln(k2/k3) as a function of 1/T are shown in
Figure 1. The “flat” temperature dependency observed in this wide
range of temperature is unprecedented, and clearly demonstrates
that the reaction is stereocontrolled by the differential activation
entropy, ∆∆Sq.13
Supporting Information Available: Experimental details and spectral
data for all new compounds (PDF). This material is available free of
charge via the Internet at http://pubs.acs.org.
JA993976O
(11) The structure of the adduct 2a-c were fully identified. The stere-
ochemistries of 2d and 3d were not determined. See the Supporting Information
for the details.
(14) For reviews, see: (a) Winnik, M. A. Chem. ReV. 1981, 81, 491-524.
(b) Nakagaki, R.; Sakuragi, H.; Murai, K. J. Phys. Org. Chem. 1989, 2, 187-
204.
(15) If the conformational equilibration of the tether part is slower than
the [2+2] addition, the de is also independent of the reaction temperature.
This anti-Curtin-Hammett explanation also leads to the same conclusion that
the chiral fate of the reaction is prearranged in the ground state. For kinetic
data for intermolecular ketene [2+2] additions, see: Issacs, N. S.; Stanbury,
P. J. Chem. Soc., Perkin Trans. 2 1973, 166-169.
(12) The ketene generated through the base-promoted 1,2-elimination from
a corresponding substrate also produced only 2a. See the Supporting
Information for the details.
(13) Contributions of ∆∆Hq to ln(k2/k3) at 300 K are only -15% for 1c
and 27% for 1d. In 1c, stereodirections of ∆∆Hq and ∆∆Sq are opposite, and
thus, the result is also regarded as the stereoselectivity caused by ∆∆Sq, which
is reduced 12% by ∆∆Hq.