Stereochemistry of thermal vinylcyclobutane-to-cyclohexene rearrangements of cis-(1S,2R)- and trans-(1S,2S)-1-(E)-propenyl-2-methylcyclobutanes [1]

Full text of DOI:10.1021/ja010987k

6718
J. Am. Chem. Soc. 2001, 123, 6718-6719
Scheme 1
Stereochemistry of Thermal Vinylcyclobutane-to-
Cyclohexene Rearrangements of cis-(1S,2R)- and
trans-(1S,2S)-1-(E)-Propenyl-2-methylcyclobutanes
John E. Baldwin* and Richard C. Burrell
Department of Chemistry, Syracuse UniVersity
Syracuse, New York 13244
ReceiVed April 18, 2001
The thermal vinylcyclopropane-to-cyclopentene and vinylcy-
clobutane-to-cyclohexene rearrangementssamong the simplest of
[1,3] carbon sigmatropic shiftsshave been known for some 40
years.1,2 Stereochemical information on the isomerizations of
substituted vinylcyclopropane hydrocarbons has been gained for
a variety of systems,3-5 and these experimental findings and
extensive theoretical work6 have provided considerable insight
on the reactions. They are stereochemically promiscuous but not
random, and appear to involve short-lived conformationally
flexible (2Z)-pentene-1,5-diyl diradicals traversing relative flat
transition regions under dynamic control.
Curiously enough, no parallel stereochemical studies on
conversions of simple substituted vinylcyclobutane hydrocarbons-
to-cyclohexenes have been reported.7 Prior work with vinylcy-
clopropane-to-cyclopentene isomerizations5 and with cyclohexene-
vinylcyclobutane interconversions and fragmentations8 piqued our
curiosity about the stereochemical aspects of vinylcyclobutane-
to-cyclohexene reactions and engendered a willingness to engage
in the experimental challenges that detailed investigations of
reaction stereochemistry would provide.
with suprafacial (s) or antarafacial (a) utilization of the allylic
unit, and retention (r) or inversion (i) at the migrating carbon;
they do not connote mechanistic implications.
An experimental effort to decipher reaction stereochemisry
would have to face complexities associated with other reactions.
The vinylcyclobutanes 1 would be expected to suffer thermal
stereomutations,9 various fragmentations, and other isomerizations
in competition with conversions to 3,4-dimethylcyclohexenes. Any
of the four possible stereoisomers 2 could be formed from any
one of the four isomers of 1, each having time-dependent concen-
trations. Thus the kinetic situation as well as the analytical
requirements might prove daunting.
The present report outlines experiments solving this problem
in reaction stereochemistry. The overall objective, to provide a
rigorous experimental definiton of reaction stereochemistry for
the thermal vinylcyclobutane-to-cyclohexene isomerizations of the
geometrically unconstrained hydrocarbons SR-1 and SS-1, was
approached in stages.
First, methods for quantitative analyses of mixtures of all four
isomers of 2 using capillary GC were developed.10 Second,
racemic samples of cis-1 and trans-1 were synthesized,11 and the
thermal reactions they exhibited at 275 °C were investigated.12
Every C8H14 isomer in reaction mixtures was well resolved by
capillary GC; each was isolated by preparative GC and identified
with the aid of authentic reference samples. Third, when attempts
to resolve the enantiomers of cis-1 and trans-1 directly through
capillary GC on columns having chiral stationary phases proved
unsuccessful, an alternative tactic was developed: preparative GC
gave pairs of enantiomers, which were converted (OsO4, NaIO4,
dioxane, H2O; then LiAlH4, ether) on a very small scale to
mixtures of the four 1-hydroxymethyl-2-methylcyclobutanes,
compounds conveniently and completely separated by GC using
a CycloSil B column (30% heptakis(2,3-di-O-methyl-6-O-tert-
butyldimethylsilyl)-â-cyclodextrin in DB-1701; J&W).
Fourth, samples of the cis-(1S,2R)- and trans-(1S,2S)-isomers
of 1-hydroxymethyl-2-methylcyclobutane (SR-3 and SS-3) of
better than 99% ee were prepared11 and assignments of absolute
stereochemistry were secured through chemical interconversions
and a reference compound structurally defined through X-ray
crystallography.13 These alcohols led to secure correlations of
enantiomers separated by GC; on the CycloSil B column the
elution order is RS-3 before SR-3, and RR-3 before SS-3. Fifth,
the alcohols SR-3 and SS-3 of high ee were converted (PCC,
CH2Cl2; then CrCl2,CH3CHI2, THF) to the corresponding 1-pro-
Stereochemically well-defined reactants, such as cis-(1S,2R)-
and trans-(1S,2S)-1-(E)-propenyl-2-methylcyclobutane (SR-1 and
SS-1), may each through [1,3] shifts of C2 give four distinct 3,4-
dimethylcyclohexenes. The correspondences between reactant and
product defined by stereochemically explicit rate constants as
exemplified in Scheme 1 may be readily extended to the full 4 ×
4 correlation matrix. For instance SR-1 gives RS-2 through rate
constant k′ , SS-2 through k′ , and RR-2 through k′ . The first-
si
order rateaiconstants k′ (for cis reactants) and k ar (for trans
mn
reactants) are coded witmhnsubscripts indicative of overall migration
(1) (a) Vogel, E. Angew. Chem. 1960, 72, 2-46. (b) Overberger, C. G.;
Boschert, A. E. J. Am. Chem. Soc. 1960, 82, 1007-1008 and 4896-4899.
(2) (a) Ellis, R. J.; Frey, H. M. Trans. Faraday Soc. 1963, 59, 2076-
2079. (b) Pottinger, R.; Frey, H. M. J. Chem. Soc., Faraday Trans. 1 1978,
74, 1827-1833. (c) Lewis, D. K.; Charney, D. J.; Kalra, B. L.; Plate, A.-M.;
Woodard, M. H.; Cianciosi, S. J.; Baldwin, J. E. J. Phys. Chem. A 1997, 101,
4097-4102.
(3) (a) Doering, W. von E; Sachdev, K. J. Am. Chem. Soc. 1975, 97, 5512-
5520. (b) Barsa, E. A. Ph.D. Dissertation, Harvard University, 1977; Diss.
Abstr. Int. B 1977, 37, 5077.
(4) (a) Gajewski, J. J.; Squicciarini, M. P. J. Am. Chem. Soc. 1989, 111, 1,
6717-6728. (b) Gajewski, J. J.; Olson, L. P. J. Am. Chem. Soc. 1991, 113,
7432-7433. (c) Gajewski, J. J.; Olson, L. P.; Willcott, M. R. J. Am. Chem.
Soc. 1996, 118, 299-306.
(5) (a) Andrews, G. D.; Baldwin, J. E. J. Am. Chem. Soc. 1976, 98, 8,
6705-6706. (b) Baldwin, J. E.; Bonacorsi, S. J.; Burrell, R. C. J. Org. Chem.
1998, 63, 4721-4725. (c) Baldwin, J. E. J. Comput. Chem. 1998, 19, 222-
231. (d) Baldwin, J. E.; Burrell, R. C. J. Org. Chem. 1999, 64, 3567-3571.
(e) Baldwin, J. E.; Shukla, R. J. Am. Chem. Soc. 1999, 121, 11018-11019.
(6) (a) Davidson, E. R.; Gajewski, J. J. J. Am. Chem. Soc. 1997, 119,
10543-10544. (b) Houk, K. N.; Nendel, M.; Wiest, O.; Storer, J. W. J. Am.
Chem. Soc. 1997, 119, 10545-10546. (c) Doubleday: C.; Nendel, M.; Houk,
K. N.; Thweatt, D.; Page, M. J. Am. Chem. Soc. 1999, 121, 4720-4721. (d)
Nendel, M.; Sperling, D.; Wiest, O.; Houk, K. N. J. Org. Chem. 2000, 65,
3259-3268.
(7) The (E,E) and (E,Z) isomers of trans-(1R,2R)-1,2-dipropenylcyclobutane
isomerize to 3-methyl-4-propenylcyclohexenes with stereochemical preferences
strongly favoring si (50.2-49.5%) and sr (41.1-46.8%) modes; see Berson,
J. A.; Dervan, P. B.; Malherbe, R.; Jenkins, J. A. J. Am. Chem. Soc. 1976,
98, 5937-5968 and ref 2 therein.
(8) (a) Lewis, D. K.; Brandt, B.; Crockford, L.; Glenar, D. A.; Rauscher,
G.; Rodriquez, J.; Baldwin, J. E. J. Am. Chem. Soc. 1993, 115, 11728-11734.
(b) Lewis, D. K.; Hutchinson, A.; Lever, S. J.; Spaulding, E. L.; Bonacorsi,
S. J.; Baldwin, J. E. Isr. J. Chem. 1996, 36, 233-238. (c) Lewis, D. K.; Glenar,
D. A.; Hughes, S.; Kalra, B. L.; Schlier, J.; Shukla, R.; Baldwin, J. E. J. Am.
Chem. Soc. 2001, 123, 996-997.
(9) Baldwin, J. E. In The Chemistry of the Cyclopropyl Group; Rappoport,
Z., Ed.; John Wiley & Sons: Chichester, 1995; Vol.2, pp 469-494.
(10) Baldwin, J. E.; Burrell, R. C. J. Org. Chem. 2000, 65, 7145-7150.
(11) Baldwin, J. E.; Burrell, R. C. J. Org. Chem. 2000, 65, 7139-7144.
(12) The thermal isomerizations shown by racemic samples of cis-1 and
trans-1 studied by L. M. Jordan (Ph.D. Dissertation, Yale University, 1974;
Diss. Abstr. Int. B 1975, 35, 5332-5333) have been summarized in Gajewski,
J. J. Hydrocarbon Thermal Isomerizations; Academic Press: New York, 1981;
pp 177-183.
(13) Alexander, J. S.; Baldwin, J. E.; Burrell, R. C.; Ruhlandt-Senge, K.
Chem. Commun. 2000, 2201-2202.
10.1021/ja010987k CCC: $20.00 © 2001 American Chemical Society
Published on Web 06/14/2001

Communications to the Editor
J. Am. Chem. Soc., Vol. 123, No. 27, 2001 6719
Scheme 2
Scheme 3
penyl-2-methylcyclobutanes with about 14:1 E/Z stereoselectivity.
Preparative GC then gave SR-1 and SS-1 for kinetic experiments.
Scheme 4
Samples of SR-1 or SS-1 and cyclooctane (as internal standard)
diluted with pentane (to serve as a bath gas) were heated in a
gas-phase quartz static reactor at 275 °C for specified periods,
then transferred to a vacuum line, condensed, and analyzed by
GC. Time-dependent mol % data for sums of cis and trans
enantiomers followed well the theoretically dictated kinetic forms.
For thermal reactions starting from the cis isomer SR-1, cis-1(t)
) 0.37 exp(-λ1t) + 99.63 exp(-λ2t) and trans-1(t) ) 30.75
exp(-λ1t) - 30.75 exp(-λ2t). For reactions from SS-1, trans-
1(t) ) 89.39 exp(-λ1t) + 10.40 exp(-λ2t) and cis-1(t) ) 6.55
exp(-λ1t) - 6.33 exp(-λ2t). For all four functions, λ1 ) 1.84 ×
10-5 s-1 and λ2 ) 9.02 × 10-5 s-1. These four time-dependent
functions reflect cis-1,trans-1 equilibrations and all fragmenta-
tions, [1,3] shifts, and other isomerizations contributing to decay
of (cis-1 + trans-1).
2. The two slopes for the linear plots give values of (k′ - k′ )
sr
ai
and (k′ - k′ ). For runs starting with SS-1, one has (SS-2 -
si
ar
RR-2)(t) ) (ksr - kai)∫(SS-1 - RR-1)dt and (SR-2 - RS-2)(t) )
(ksi - kar)∫(SS-1 - RR-1)dt. The linear plots provide measures
of (ksr - kai) and (ksi - kar).
From the experimentally determined rate constant sums and
differences one may derive all eight rate constants for distinct
[1,3] carbon sigmatropic shifts, or the relative importance of the
stereochemically different paths utilized by each reactant (Scheme
3, in percentage terms, (2-3%).
Several points are worth noting. An enantiomer of trans-1
reacts using the four possible paths in a pattern similar to the
one uncovered in 1976 for trans-1-(E)-propenyl-2-methycyclo-
propane - 65% si, 8% ar, 22% sr and 5% ai.5a One may thus
anticipate that the sorts of theoretical efforts which have provided
illuminating insights for vinylcyclopropane-to-cyclopentene isomer-
izations6 may be directly relevant to the similar isomerizations
of vinylcyclobutanes. The stereochemical pattern for one enan-
tiomer of cis-1 is quite dissimilar, however, for the most prominent
sr and ai paths seen experimentally are “forbidden” by orbital
symmetry theory. The dictates of orbital symmetry for these
reactions seem irrelevant. Rather, relative product stabilities and
entropic factors may control reaction dynamics and stereochemical
outcomes for these isomerizations.
At any time t, the rate of formation of cis product is d(cis-2)/
dt ) d(SS-2 + RR-2)/dt ) (k′ + k′ )(SR-1 + RS-1) + (ksr
+
ar
kai)(SS-1 + RR-1). Integration spi rovides (SS-2 + RR-2)(t) ) (k′
+ k′ )∫(SR-1 + RS-1)dt + (ksr + kai)∫(SS-1 + RR-1)dt. Thissi
and atrhe similar expression for trans-2(t) ) (SR-2 + RS-2)(t) and
the time-dependent GC-determined values of cis-2 and trans-2
led through least-squares optimizations to the rate constants (k′
si
+ k′ ) ) 2.19 × 10-6 s-1, (k′ + k′ ) ) 5.34 × 10-6 s-1, (ksr +
ar
sr
kai) ) 1.45 × 10-6 s-1, and (ksi + akiar) ) 2.44 × 10-6 s-1
.
The time-dependent values of (SR-1 - RS-1) and (SS-1 -
RR-1) starting from either SR-1 or SS-1 were, as the relevant
kinetic expressions require, well modeled as a sum of two
exponential terms. For reactions starting from SR-1, (SR-1 - RS-
1)(t) ) 1.27 exp(-λ3t) + 97.73 exp(-λ4t) and (SS-1 - RR-1)(t)
) 4.37 exp(-λ3t) - 4.37 exp(-λ4t). For reactions starting from
SS-1, (SS-1 - RR-1)(t) ) 89.44 exp(-λ3t) + 9.35 exp(-λ4t),
where λ3 ) 2.20 × 10-5 s-1 and λ4 ) 10.57 × 10-5 s-1, and
(SR-1 - RS-1)(t) ) 0 to within experimental uncertainties.
These functions and time-dependent GC-determined values for
(SS-2 - RR-2) and for (SR-2 - RS-2) then provided the rate
constants (k′ - k′ ) ) 0.57 × 10-6 s-1, (k′ - k′ ) ) 2.41 × 10-6
s-1, (ksr - ksaii) ) a1r.12 × 10-6 s-1, and (kssir- kaari) ) 2.08 × 10-6
s-1 from simple linear plots based on the exact integrated kinetic
expressions. The kinetic situation for the formation of cis-3,4-
dimethylcyclohexenes illustrates the analysis (Scheme 2).
At any time t, d(SS-2 - RR-2)/dt ) (k′ - k′ )(SR-1 - RS-1)
Comparable stereochemical findings were attained by Doering
and Cheng in 1989 for racemic 1-(E)-propenyl-2-cyanocyclobu-
tanes labeled stereoselectively with deuterium at C3 and C4.14
The relative importance of the various reaction modes, rounded
to the nearest percent (Scheme 4), are remarkably similar. Again,
the cis isomer favors “forbidden” paths; the “allowed” si com-
ponent prominent for the trans reactant is strikingly diminished
in isomerizations shown by the cis substrate.
The differences in stereochemical preferences for the 1-(E)-
propenyl-2-methylcyclobutanes SR-1 and SS-1 underscore both
the substantial influences the spatial dispositions of methyl
substituents exert on reaction dynamics and the need for complete
stereochemical information on the vinylcyclobutane-to-cyclohex-
ene isomerizations shown by systems with only truly minimal
stereochemistry-marking substituents: deuterium atoms. Such an
undertaking lies in the future.
si
ar
Acknowledgment. We thank the National Science Foundation, for
support of this work through CHE-9902184, and Professor William von
Eggers Doering, Harvard University, for most valuable correspondence
and discussions.
+ (ksr - kai)(SS-1 - RR-1). Integration provides (SS-2 - RR-2)-
(t) ) (k′ - k′ )∫(SR-1 - RS-1)dt + (ksr - kai)∫(SS-1 - RR-1)-
ar
dt. The siintegrals may be calculated for any range 0 to t, and the
equation rearranged to standard y ) mx + b form: (SS-2 -
Supporting Information Available: Four figures displaying kinetic
data and derived theory-based functions (PDF). This material is available
free of charge via the Internet at http://pubs.acs.org.
RR-2)(t)/∫(SS-1 - RR-1)dt ) (k′ - k′ )∫ (SR-1 - RS-1)dt/∫
ar
(SS-1 - RR-1)dt + (ksr - kai). Ssiimilarly, (SR-2 - RS-2)(t) )
(k′ - k′ )∫ (SR-1 - RS-1)dt + (ksi - kar)∫(SS-1 - RR-1)dt
sr
ai
JA010987K
and (SR-2 - RS-2)(t)/∫(SS-1 - RR-1)dt ) (k′ - k′ )∫ (SR-1 -
sr
ai
RS-1)dt/∫ (SS-1 - RR-1)dt + (ksi - kar) serve for treating time-
(14) Cheng, X. Ph.D. Dissertation, Harvard University, 1989; Diss. Abstr.
Int. B 1990, 50, 3472.
dependent data for reactions leading to the enantiomers of trans-