Wagner-Meerwein rearrangements in the gas phase: Deuterium isotope effects on acid-induced dissociation of optically active phenylpropanols

Article abstract of DOI:10.1002/(SICI)1521-3765(19990301)5:3<845::AID-CHEM845>3.0.CO;2-8

The deuterium isotope effects on the kinetics of H₂O loss from O- protonated (S)-1-phenyl-2-propanol (1s(H+)) and (S)-2-phenyl-1-propanol (2S(H+)) have been investigated in the gas phase at 750 Torr and at 25 °C. The measured primary and second

Full text of DOI:10.1002/(SICI)1521-3765(19990301)5:3<845::AID-CHEM845>3.0.CO;2-8

FULL PAPER
Chiral Ions in the Gas Phase, Part 7 [= ]
Wagner± Meerwein Rearrangements in the Gas Phase: Deuterium Isotope
Effects on Acid-Induced Dissociation of Optically Active Phenylpropanols
Maurizio Speranza* and Antonello Filippi[a]
Abstract: The deuterium isotope effects
of the relevant activation parameters
reported in the preceding paper, is
consistent with: i) a phenyl-group par-
ticipation transition state (TS) structure,
which is placed rather early along the
reaction coordinate and in which the
participation, in which
a
limited
‡
on the kinetics of H O loss from O-pro-
C �OH bond cleavage is fully out-
2
a
2
tonated (S)-1-phenyl-2-propanol (1sH
‡
)
)
weighed by the advanced H(D)�C
a
and (S)-2-phenyl-1-propanol (2sH
‡
bonding, and iii) a borderline TS struc-
have been investigated in the gas phase
at 750 Torr and at 258C. The measured
primary and secondary a-D , b-D , and
ture for the b-methyl group participa-
tion in 2sH
‡
, in which intense Me�Ca
‡
partial C �OH bond cleavage is cou-
bonding is coupled with a pronounced
1
1
a
2
‡
b'-D3 kinetic isotope effects provide
conclusive evidence on the detailed
mechanism of the gas-phase dissociation
pled with a weak Ph-C interaction, ii) a
C �OH bond elongation. The values
a
a
2
tight TS structure for the b-hydrogen
of the primary and secondary a-D , b-
1
D , and b'-D3 kinetic isotope effects,
1
of 1sH
‡
and 2sH
‡
; this involves compet-
measured in the present gas-phase in-
vestigation, are discussed and compared
with those of related gas-phase and
solvolysis reactions.
Keywords: anchimeric assistance ´
chirality ´ gas-phase chemistry ´ ki-
netic isotope effects ´ phenonium ions
ing anchimeric assistance from all the
groups adjacent to the reaction center
(
C ). Their analysis, combined with that
a
Introduction
appears to be governed, in the gas phase, more by entropic
than by enthalpic factors. In view of the relative stability of the
1sH‡ and 2sH‡ rotamers (Scheme 1), the largely different pre-
exponential terms for their dissociation pathways cannot be
accounted for by conformational equilibria. Rather, they must
be determined by the specific features of the corresponding
transition state (TS) structures and their positions along the
dissociation coordinate.
In the preceding paper of this issue,[1] the kinetics and the
mechanisms of the unimolecular H O loss from O-protonated
2
(
S)-1-phenyl-2-propanol (1sH
‡
) and O-protonated (S)-2-phe-
nyl-1-propanol (2sH ; Figure 1) were investigated in the gas
phase, that is, under conditions excluding nucleophilic assis-
‡
tance by the solvent (k ), which generally interferes with
S
anchimeric assistance (k ) in analogous b-arylalkyl solvoly-
The aim of the present investigation is to characterize the
nature of the TS structures involved in the potential energy
profiles of Figure 1. Primary and secondary kinetic isotope
effects are widely recognized as being among the most reliable
tools for investigating reaction mechanisms, in the sense that
they provide unique and direct information about the TS
structure of the reaction.[ In this context, deuterium primary
(PKIEs) and secondary kinetic effects (SKIEs) have been
extensively applied in the condensed phase for establishing
the mechanism of b-arylalkyl solvolysis, especially in con-
D
[
2±5]
ses.
ular dissociation of 1sH
assisted by all the groups adjacent to the leaving H O moiety,
The results are consistent with a gas-phase unimolec-
‡
and 2sH that is anchimerically
‡
2
that is, the phenyl group and the hydrogen atom in 1sH
‡
, and
the phenyl and methyl groups, and the hydrogen atom in 2sH
‡
.
6]
According to the relevant activation parameters of Figure 1,
kinetic competition among these genuine kD processes
[
a] Prof. M. Speranza, Dr. A. Filippi
Facolt aÁ di Farmacia, Dipartimento No. 64
nection with the discrimination between anchimeric-assisted
(
Chimica e Tecnologia delle Sostanze Biologicamente Attive)
[4c, 6±8]
(
k ) and solvent-assisted (k ) reaction profiles.
S
D
Universit aÁ di Roma La Sapienza
P.le A. Moro 5, 00185 Rome, Italy
Fax : (‡ 390)6-49913602
Following the same approach, the competition kinetics of
the unimolecular H O loss from 1s and their
‡
H
and 2sH
‡
2
E-mail: speranza@axrma.uniroma1.it
deuterated analogues have been examined in the gas phase,
[=] Part 6: A Filippi, M. Speranza, preceding paper in this issue.
namely, in the absence of solvent assistance (k ), under
S
Chem. Eur. J. 1999, 5, No. 3
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845

M. Speranza, A. Filippi
FULL PAPER
Scheme 1. Order of stability of the conformers of O-protonated (S)-1-
phenyl-2-propanol and (S)-2-phenyl-1-propanol.
experimental conditions as those outlined in the preceding
16
paper, with the only exception of the use of CH OH, instead
3
of CH318OH, as the external nucleophile. Thereby we hoped
[1]
to elucidate the nature of the TS structures involved in the
neighboring-group assistance in the H O loss and their
2
sensitivity to environmental effects by comparing the gas-
phase deuterium PKIEs and SKIEs with those measured in
analogous solvolysis processes.
2
Figure 1. Energy profiles for adjacent group participations to H O loss in
O-protonated (S)-1-phenyl-2-propanol (1sH‡) and O-protonated (S)-2-
phenyl-1-propanol (2sH‡). The bold figures refer to the DE* and the italic
ones to DlogA* (ref. [1]).
Experimental Section
Materials: Methane and oxygen were high purity gases from Matheson and
were used without further purification. (S)-1-phenyl-2-propanol (1s) and
its R-enantiomer (1r), (S)-2-phenyl-1-propanol (2s) and its R-enantiomer
Abstract in Italian: Gli effetti dellꢀisotopo deuterio sulla
(
2r), (S)- and (R)-1-phenyl-1-propanol, and 2-phenyl-2-propanol were
cinetica di eliminazione di H O in protonati allꢀossigeno
2
research grade chemicals from Aldrich. The (R,R)/(S,S)-racemate of
1-phenyl-1-deutero-2-propanol (1b*) was synthesized, together with the
(
S)-1-fenil-2-propanolo (1sH
‡
) e (S)-2-fenil-1-propanolo (2sH )
‡
(
R,S)/(S,R) racemate of 1-phenyl-2-deutero-1-propanol, by reaction of
sono stati studiati in fase gassosa a 750 Torr ed a 258C.
Lꢀeffetto isotopico primario e gli effetti isotopici secondari tipo
trans-b-methyl-styrene with LiAlD and subsequent oxidation with hydro-
4
[
9]
gen peroxide. The same procedure was employed to prepare the (R)/(S)-
racemate of 2-phenyl-2-deutero-1-propanol (2b) from a-methyl-styrene.
The (R)/(S)-racemate of 1-phenyl-2-deutero-2-propanol (1a) was prepared
a-D , b-D , e b'-D forniscono un quadro conclusivo del
1
1
3
meccanismo di dissociazione di 1sH
‡
e 2sH in fase gassosa, che
‡
procede attraverso lꢀassistenza anchimerica da parte di tutti i
by LiAlD
racemate of 2-phenylpropionaldehyde yields the mixture of the (R,R)/
S,S)- and (R,S)/(S,R)-racemates of 2-phenyl-1-deutero-1-propanol (2a).
The (R)/(S)-racemate of 1-phenyl-3,3,3-trideutero-2-propanol (1bbb) was
synthesized by treating phenylacetaldehyde with CD MgI. The deuterium
content of these labeled alcohols was determined by NMR spectroscopy
and GLC ± MS analysis. All of them display a D content exceeding 98%.
The equimolar mixture of both (R,R)/(S,S)- and (R,S)/(S,R)-racemates of
4
reduction of phenylacetone. The same reaction with the (R)/(S)-
gruppi adiacenti al centro di reazione (C ). Lꢀanalisi degli
a
(
effetti isotopici, combinata con quella dei corrispondenti
parametri di attivazione riportati nel lavoro precedente, indica:
i) una collocazione piuttosto anticipata sulla coordinata di
reazione per estato di transizione (TS) della partecipazione del
gruppo fenile in cui una debole interazione fra il gruppo Ph ed
il centro Ca corrisponde alla estesa rottura del legame
3
1
-phenyl-1-deutero-2-propanol (1b) was obtained, together with the
unlabeled product (rac-1) and minor amounts of the (R)/(S) racemate of
1-phenyl-1,1-dideutero-2-propanol (1bb), by D O exchange of phenyl-
acetone in dioxane/pyridine solutions and subsequent LiAlH reduction of
NMR and GLC ± MS analyses are
‡
C �OH ; ii) una struttura compatta per lo TS della parteci-
a
2
2
pazione dellꢀatomo di idrogeno in beta in cui una intensa
interazione fra lꢀatomo H ed il centro C corrisponde ad una
4
[
8a]
the variously deuterated ketones.
b
a
consistent with a [rac-1]:[1b]:[1bb] ˆ 4.8:3.2:1.0 distribution. The methyl
ethers of the above alcohols were synthesized by the dimethyl sulfate
method, and their configurations were assigned according to the starting
‡
limitata rottura del legame C �OH ; iii) una struttura
a
2
intermedia per lo TS della partecipazione del gruppo Me
metile in beta in cui una intensa interazione fra il gruppo Meb
[
10]
alcohol. In this way, (S)- (3s) and (R)-1-phenyl-2-methoxypropane (3r)
were obtained from 1s and 1r, respectively, (S)- (4s) and (R)-2-phenyl-1-
methoxypropane (4r) from 2s and 2r, respectively, (S)- (5s) and (R)-1-
phenyl-1-methoxypropane (5r) from (S)- and (R)-1-phenyl-1-propanol,
respectively, and 2-phenyl-2-methoxypropane (6) from 2-phenyl-2-prop-
anol. In the same way, all the isomers of 1-phenyl-2-deutero-2-methoxy-
propane (3a), 1-phenyl-1-deutero-2-methoxypropane (3b), 1-phenyl-1,1-
dideutero-2-methoxypropane (3bb), and 1-phenyl-3,3,3-trideutero-2-
ed il centro C corrisponde ad una pronunciata elongazione del
a
‡
legame C �OH . I valori degli effetti isotopici primario e
a
2
secondari, misurati negli esperimenti in fase gassosa, sono
esaminati alla luce di corrispondenti dati raccolti sia in fase
gassosa che in soluzione.
8
46
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Chem. Eur. J. 1999, 5, No. 3

Wagner ± Meerwein Rearrangements
845±853
Table 1. Characteristic mass spectrometric peaks of the radiolytic products.
Isotopomer
Symbol[a]
m/z (parent)
m/z (fragment)
1
-Phenyl-2-methoxypropanes (3):
.
.
‡
‡
.
‡
PhCH
PhCH
PhCHDCH(CH
PhCD
PhCH
2
CH(CH
CD(CH
3
3
)OMe
)OMe
rac-3
3a
3b
3bb
3bbb
150 ([PhCH
151 ([PhCH
151 ([PhCHDCH(CH
152 ([PhCD
153 ([PhCH
2
CH(CH
CD(CH
3
3
)OMe]
)OMe]
)
)
59 ([MeOCHCH
60 ([MeOCDCH
59 ([MeOCHCH
59 ([MeOCHCH
62 ([MeOCHCD
3
3
3
3
3
] )
‡
2
2
] )
‡
‡
3
)OMe
3
)OMe]
)
] )
.
.
‡
‡
‡
2
CH(CH
CH(CD
3
)OMe
)OMe
2
CH(CH
CH(CD
3
)OMe]
)OMe]
)
)
] )
‡
2
3
2
3
] )
1
-Phenyl-1-methoxypropanes (5):
.
.
‡
‡
.
.
‡
PhCH(OMe)CH
PhCD(OMe)CH
PhCH(OMe)CHDCH
PhCD(OMe)CHDCH
2
CH
CH
3
rac-5
5a
5b
5ab
5ggg
150 ([PhCH(OMe)CH
151 ([PhCD(OMe)CH
151 ([PhCH(OMe)CHDCH
152 ([PhCD(OMe)CHDCH
2
CH
CH
3
3
]
]
)
)
121 ([PhCH(OMe)] )
‡
2
3
2
122 ([PhCD(OMe)] )
‡
‡
‡
3
3
3
]
]
)
)
121 ([PhCH(OMe)] )
‡
3
122 ([PhCD(OMe)] )
.
‡
‡
PhCH(OMe)CH
2
CD
3
153 ([PhCH(OMe)CH
2
CD
3
]
)
121 ([PhCH(OMe)] )
2
-Phenyl-2-methoxypropanes (6):
‡
PhC(CH
PhC(CH
3
)
2
OMe
6
6b
135 ([PhC(CH
136 ([PhC(CH
3
2
3
)OMe] )
‡
3
)(CH D)OMe
2
D)OMe] )
‡
1
35 ([PhC(CH
)OMe] )
[
a] The greek letter denotes the position of the label relative to the methoxy group.
methoxypropane (3bbb) were synthesized from 1a, 1b, 1bb, and 1bbb,
respectively. All the isomers of 2-phenyl-1-deutero-1-methoxypropane
The presence and the specific position of the deuterium
label in the radiolytic ethers, obtained from mixtures con-
taining the deuterated isotopomers of the same starting
alcohols, are determined from their 70 eV MS fragmentation
patterns, which are dominated by C �C bond fission. The
(
4a) and of 2-phenyl-2-deutero-1-methoxypropane (4b) were prepared
from 2a and 2b, respectively. Finally, the 1-phenyl-2-deutero-1-methoxy-
propanes (5b) were produced from the (R,S)/(S,R) racemate of 1-phenyl-2-
deutero-1-propanol. All the alcoholic and the ethereal compounds were
purified by preparative GLC on a 2 m long, 4 mm inner diameter, stainless
steel column packed with 10% SP-1000 on 100-120 Supelcoport, at 1808C.
Their final purity exceeded 99.95%. The identity of the above alcohols and
of their methyl ethers was verified by NMR spectroscopy and their purity
assayed by GLC and GLC ± MS on the same columns employed for the
analysis of the irradiated mixtures.
a
b
ionic fragments used for these purposes are listed in Table 1.
Table 2 displays the relative abundance of the characteristic
mass spectrometric signals (Table 1) of isotopomeric ethers 3
Table 2. Relative abundance of characteristic mass spectrometric frag-
‡
ments of the products from the gas-phase attack of C
n
H
5
(n ˆ 1, 2) ions on
Procedure: The experimental techniques used for the preparation of the
1
s and its deuterated isotopomers.
gaseous mixtures and their irradiation are described in the preceding
System composition [Torr][a]
H-substrate D-substrate CH
3
16OH
Products Peak intensity ratios[b]
paper.[ The irradiations were carried out at 258C in Co g source to a dose
1]
60
4
4
� 1
of 2 Â 10 Gy at a rate of 1 Â 10 Gyh , as determined by a neopentane
4
dosimeter. Control experiments, carried out at doses ranging from 1 Â 10
1
1
s, 0.140
s, 0.130
1a, 0.140
1.23
3
5
c ˆ [59]/[60] ˆ 1.11
5
to 1 Â 10 Gy, showed that the relative yields of products are largely
g ˆ [150]/[151] ˆ 1.09
independent of the dose. The radiolytic products were analyzed by GLC,
with a Perkin ± Elmer 8700 gas chromatograph equipped with a flame
ionization detector, on a 25 m long, 0.25 mm inner diameter, MEGADEX
DACTBS-b (30% diacetyl-tert-butylsilyl-b-cyclodextrin in OV1701) fused
silica column operated at temperatures ranging from 40 to 1708C,
1b*, 0.136
1.23
1.12
3
5
5
f ˆ [59]
S
/[59]
R
ˆ 2.33
d ˆ [121]/[122] ˆ 2.96
g ˆ [150]/[151] ˆ 1.46
rac-1, 0.144 1b, 0.096
1bb, 0.030
5
5
5
d ˆ [121]/[122] ˆ 2.60
g ˆ [150]/[151] ˆ 1.68
h ˆ [152]/[151] ˆ 0.28
�
1
4
8Cmin . The products were identified by comparison of their retention
volumes with those of authentic standard compounds and their identity
confirmed by GLC ± MS, with a Hewlett ± Packard 5890A gas chromato-
graph in line with an HP 5970B mass spectrometer (GC-MS). Their yields
were determined from the areas of the corresponding eluted peaks, by use
of the internal standard (i.e. benzyl alcohol) method and individual
calibration factors to correct for the detector response. Blank experiments
were carried out to exclude the occurrence of thermal isomerization and
racemization of the starting alcohols and the corresponding methyl ethers
within the temperature range investigated.
1s, 0.116
1bbb, 0.120 1.23
3
5
1 ˆ [59]/[62] ˆ 1.03
s ˆ [150]/[153] ˆ 1.04
4
[
a] Tˆ 258C; CH
4
� 1
: 750 Torr; O
2
: 4 Torr; radiation dose 2 Â 10 Gy (dose
4
rate: 1 Â 10 Gyh ). [b] Standard deviation: ꢀ3%.
and 5, obtained from g irradiation of mixtures of alcohol 1s
and its deuterated isotopomers as the starting substrates.
Table 3 shows the relative abundance of the characteristic
mass-spectrometric fragments (Table 1) of isotopomeric
ethers 3, 5, and 6, recovered from mixtures with alcohol 2s
and its deuterated isotopomers as the starting compounds.
The figures in the tables represent mean ratios obtained from
many mass spectrometric measurements with several separate
irradiations carried out under the same experimental con-
ditions, whose reproducibility is expressed by the uncertainty
level quoted.
Results
As described in the preceding paper,[1] g irradiation at room
temperature of gaseous CH (750 Torr) mixtures containing
4
alcohol 1s, as the substrate, O (4 Torr), as a thermal radical
2
scavenger, and CH31 OH (ca. 3 Torr), as an external nucleo-
phile, yields the (S)-1-phenyl-2-methoxypropanes (3s) and
the racemate of 1-phenyl-1-methoxypropane (rac-5) as pre-
dominant products. If the starting alcohol is 2s, the major
products are (S)-1-phenyl-2-methoxypropanes (3s), the race-
mate of 1-phenyl-1-methoxypropane (rac-5), and 2-phenyl-2-
methoxypropane (6).
6
Comparative analysis of the mass spectra of the 3, 5, and 6
isotopomeric families of Table 1 exclude any appreciable
isotope effect in their fragmentation patterns. However, an
imbalance between the m/z 135 (48.5%) versus m/z 136
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M. Speranza, A. Filippi
FULL PAPER
Table 3. Relative abundance of characteristic mass spectrometric frag-
‡
ments of the products from the gas-phase attack of C
n
H
5
(n ˆ 1, 2) ions on
2
s and its deuterated isotopomers.
System composition [Torr][a]
H-substrate D-substrate CH
3
16OH
Products Peak intensity ratios[b]
2
2
s, 0.134
s, 0.101
2a, 0.108
2b, 0.090
0.86
3
5
5
6
f ˆ [59]
S
/[59]
R
ˆ 3.23
g ˆ [150]/[151] ˆ 1.25
d ˆ [121]/[122] ˆ 10.06
e ˆ [135]/[136] ˆ 3.06
0.92
3
5
5
6
c ˆ [59]/[60] ˆ 1.31
g ˆ [150]/[151] ˆ 1.25
d ˆ [121]/[122] ˆ 4.01
e ˆ [135]/[136] ˆ 5.17
4
[
a] Tˆ 258C; CH
4
� 1
: 750 Torr; O
2
: 4 Torr; radiation dose 2 Â 10 Gy (dose
4
rate: 1 Â 10 Gyh ); [b] Standard deviation: ca. 3%.
(51.5%) peak intensities of 6b is observed. An appreciable
difference in the fragmentation patterns of unlabeled and
labeled ethers is observed only in the case of rac-3 (m/z 59:
m/z 150 ˆ 0.87) and of its trideuterated isotopomer 3bbb (m/z
6
2
2: m/z 153 ˆ 1.08). In this case, the D content in the 1-phenyl-
-methoxypropanes (3) arising from the 1s/1bbb starting
mixtures is determined by considering only the relative
abundances of the peaks corresponding to the molecular ions
Scheme 2. Reaction pattern from gas-phase O-protonation of (S)-1-
phenyl-2-propanol in the presence of methanol.
(
m/z 150, 153). The D content in all the other products has
been calculated from the relevant peak intensities after
correction for the natural isotopic contributions.
Discussion
Kinetic patterns: As outlined in the preceding paper,[1]
radiolysis of the bulk CH gas generates known yields of the
g
4
‡
[11]
strong C H5 (n ˆ 1, 2) Brùnsted acids. Once collisionally
n
thermalized, these ions indiscriminately attack all the nucleo-
philes present in the mixture, including the alcoholic substrate
and its isotopomer, yielding the corresponding O-protonated
derivatives in proportions that reflect the molar fraction of
their alcoholic precursor. Once formed, the O-protonated
derivatives of the starting alcohols undergo, in the gas
phase, extensive unimolecular H O loss, anchimerically
2
assisted by all the groups adjacent to the leaving moiety.
‡
The so-formed [C H ] species (and their isotopomers)
9
11
1
6
are trapped by the external CH3 OH nucleophile well-
1
6
‡
before further rearrangements. The [C H � O(H)Me]
9
11
adducts are neutralized by fast proton loss to a suitable base
and eventually yield the ethereal products listed in Tables 2
[
12]
and 3.
Therefore, the products in Table 2 are generated by the
reaction network in Scheme 2 (the Fischer-type projections
reported in Schemes 2 ± 9 do not reflect any specific config-
uration, but rather represent the racemates of the relevant
products), which involves competing neighboring-group as-
sistance in the unimolecular C�O bond cleavage of the 1s
‡
H
Scheme 3. Reaction pattern from gas-phase O-protonation of (S)-2-
phenyl-1-propanol in the presence of methanol.
precursor. A similar competition network (Scheme 3) ac-
counts for the formation of the products in Table 3. In this
respect, the formation at 258C of both ethers 5a (60%) and
1]
5
b (40%) from 2-phenyl-2-deutero-1-propanol (2b)[ indi-
assisted by the adjacent methyl group (2sH
in Scheme 3) or by the vicinal phenyl moiety (2sH
k in Scheme 3). In this latter case the [Ir‡H O] complex
5
‡
!IVs !rac-5; k
4
cates that these products arise from two different pathways
involving H O departure from 2s ; this is anchimerically
‡
![Ir‡H O];
2
‡
2
H
2
8
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Wagner ± Meerwein Rearrangements
845±853
undergoes trapping by CH316OH to yield 3s (Ir‡
CH316OH !3s; (1 � a)k in Scheme 3), in competition with
5
exothermic back condensation to 1s
‡
(Figure 1; [Ir‡H O] !
H
2
1
sH
‡
; ak in Scheme 3). The so-formed 1s
‡
product then
5
H
follows the reaction pattern given in Scheme 2 to yield the
1
-phenyl-1-methoxypropanes rac-5 (1sH
‡
!IVs !rac-5; k in
1
Scheme 2). Of course, if the starting alcohol is 2b instead of
2
s, H O loss from the O-protonated substrate (2bH ) may
‡
2
either involve anchimeric assistance by the methyl group to
produce 5a or, alternatively, by the phenyl group to yield both
3
a and 5b (Scheme 4).
Scheme 5. Reaction pattern from gas-phase O-protonation of the diaster-
eomeric mixture of 2-phenyl-1-deutero-1-propanol in the presence of
methanol.
Scheme 4. Reaction pattern from gas-phase O-protonation of the race-
mate of 2-phenyl-2-deutero-1-propanol in the presence of methanol.
Following the same general pattern, the reaction network
promoted by O-protonation of 2-phenyl-1-deutero-1-propa-
nol (2a) is shown in Scheme 5. Schemes 6 ± 9 illustrate the
reaction networks induced by O-protonation of 1-phenyl-2-
deutero-2-propanol (1a), 1-phenyl-1-deutero-2-propanol
(
1b), 1-phenyl-1,1-dideutero-2-propanol (1bb), and 1-phe-
nyl-3,3,3-trideutero-2-propanol (1bbb), respectively.
The deuterium PKIEs and SKIEs on the vicinal-group
participation of H O loss from O-protonated 1-phenyl-2-
2
propanol can be calculated from the enantiomeric distribution
and the fragmentation patterns of the relevant ethereal
products reported in Table 2.
Scheme 6. Reaction pattern from gas-phase O-protonation of the race-
mate of 1-phenyl-2-deutero-2-propanol in the presence of methanol.
1
6
) According to the kinetic patterns shown in Schemes 2 and
Ï
dissociation and is derived from the g[1a]/[1s] ratio, with g ˆ
, the k /k ratio [Eq. (1)] represents the secondary kinetic
2
13
[
m/z 150]:[m/z 151] measured from the ionization of the
isotope effect by one deuterium atom located in the a position
with respect to the leaving moiety in the phenyl-group
participation ([a-D -SKIE] ) in the loss of H O from
etheral products 5.
1
Ph
2
k
2
/k13 ˆ [a-D
1
-SKIE]Ph ˆ c[1a]/[1s]
(1)
(2)
O-protonated 1-phenyl-2-propanol, and it is simply calculated
from the c ˆ [m/z 59]:[m/z 60] ratio from the etheral products
k1/k12 ˆ [a-D -SKIE] ˆ g[1a]/[1s]
1
H
3
recovered from 1s ‡ 1a systems after correction for the
relative concentration of the starting alcohols. Similarly, the
k /k ratio [Eq. (2)] represents the [a-D -SKIE] for the same
2) The enantiomeric distribution of the ethereal products 3
from irradiation of the 1s/1b* systems (Schemes 2 and 7)
1
12
1
H
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849

M. Speranza, A. Filippi
FULL PAPER
allows us to evaluate the k /k ratio, which represents the [b-
2
16
D -SKIE] for the loss of H O from O-protonated 1-phenyl-
1
Ph
2
2
-propanol. From [m/z 59] ꢁ 0.87k [1s] ‡ 0.50k [1b*] and
S
2
16
[
m/z 59] ꢁ 0.13k [1s] ‡ 0.50k [1b*], Equation (3) can be
R
2
16
derived in which f ˆ [m/z 59] /[m/z 59] . The [b-D -PKIE]
S
R
1
and [b-D -SKIE] for the loss of H O from O-protonated
1
H
2
1
-phenyl-2-propanol cannot be simply evaluated from the
analysis of the etheral products 5 from the irradiated 1s/1b*
systems. In fact, the relative rates of formation of these
products are affected not only by the kinetic deuterium
effects, but also by the relative population of active con-
formers (Scheme 1) and the activation parameters governing
their prototropic rearrangement.[ To overcome this diffi-
culty, we resorted to the analysis of the etheral products 5
from the irradiated [rac-1]:[1b]:[1bb] ˆ 4.8:3.2:1.0 mixtures
13]
(Schemes 2, 7, and 8), as described below.
Scheme 7. Reaction pattern from gas-phase O-protonation of the diaster-
eomeric mixture of 1-phenyl-1-deutero-2-propanol in the presence of
methanol.
k2/k16 ˆ [b-D -SKIE] ˆ {0.50(f � 1)[1b*]}/{(0.87 � 0.13f)[1s]}
(3)
1
Ph
3
) The synthetic procedure for the formation 1b and 1bb
(see Experimental Section) was specifically designed to
generate all the possible configurations of 1-phenyl-2-prop-
anol with the deuterium label at C1. In this way, all the
objections raised in the point 2,[ concerning the 0.5k /k ˆ
13]
1
14
[
b-D -PKIE] and 0.5k /k ˆ [b-D -SKIE] equivalence, are
1
1
15
1
H
removed (the 0.5 term accounts for the different statistics of
hydrogen migration in rac-1 and in 1b). Thus, from the
analysis of the etheral products 5 obtained from the irradiated
[
rac-1]:[1b]:[1bb] ˆ 4.8:3.2:1.0 mixtures (Schemes 2, 7, and 8),
we get [m/z 121] ꢁ k [rac-1] ‡ k [1b]; [m/z 122] ꢁ k [1b] ‡
1
14
15
k [1bb]; [m/z 150] ꢁ k [rac-1]; [m/z 151] ꢁ (k ‡ k )[1b];
17
1
14
15
[
m/z 152] ꢁ k [1bb]. Thereby, the expressions given in
17
Equations (4) ± (7) can be derived in which gˆ [m/z 150]/[m/z
1
51], d ˆ [m/z 121]/[m/z 122], and h ˆ [m/z 152]/[m/z 151].
0
.5k
.5k
1
1
/k14 ˆ [b-D
/k15 ˆ [b-D
1
1
-PKIE] ˆ {0.5g(d ‡ 1)[1b]}/{[d(h ‡ 1)-g][rac-1]}
-SKIE]
ˆ {0.5g(d ‡ 1)[1b]}/{(g ‡ 1 � dh)[rac-1]}
-PKIE] ˆ {(g ‡ 1 � dh)[1bb]}/{0.5[h(d ‡ 1)][1b]}
-SKIE]
ˆ {(d(h ‡ 1) � g)[1bb]}/{0.5[h(d ‡ 1)][1b]}
(4)
(5)
(6)
(7)
0
H
Scheme 8. Reaction pattern from gas-phase O-protonation of the race-
mate of 1-phenyl-1,1-dideutero-2-propanol in the presence of methanol.
k
k
15/0.5k17 ˆ [b-D
14/0.5k17 ˆ [b-D
2
2
H
4
) According to the kinetic patterns shown in Schemes 2
and 9, the k /k ratio [Eq. (8)] represents the [b'-D -SKIE]
Ph
2
20
3
for the loss of H O from O-protonated 1-phenyl-2-propanol
2
and is simply calculated from the 1 ˆ [m/z 59]:[m/z 62] ratio of
the etheral products 3 recovered from 1s/1bbb systems after
correction for the relative concentration of the starting
alcohols, that is, 1[1bbb]/[1s]. Similarly, the k /k ratio
1
19
[
Eq. (9)] represents the [b'-D -SKIE] for the same dissoci-
3 H
ation and is derived from the s[1bbb]/[1s] ratio, s ˆ [m/z
50]:[m/z 153], measured from the ionization of the etheral
products 5.
1
k
k
2
1
/k20 ˆ [b'-D
/k19 ˆ [b'-D
3
3
-SKIE]Ph ˆ 1[1bbb]/[1s]
-SKIE]
ˆ s[1bbb]/[1s]
(8)
(9)
H
In the same way, the deuterium PKIE and SKIEs on the
vicinal group participation to H O loss from O-protonated
Scheme 9. Reaction pattern from gas-phase O-protonation of the race-
mate of 1-phenyl-3,3,3-trideutero-2-propanol in the presence of methanol.
2
8
50
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Wagner ± Meerwein Rearrangements
-phenyl-1-propanol can be calculated from the enantiomeric
845±853
2
Kinetic isotope effects: An additional piece of evidence in
distribution and the fragmentation patterns of the relevant
ethereal products reported in Table 3.
favor of the intervention of competing anchimeric assistance
in the H O loss from 1s
‡
H
and 2sH arises from the evaluation
‡
2
1
4
) According to the kinetic patterns shown in Schemes 3 and
, and within the reasonable assumption that no appreciable
of the relevant kinetic isotope effects, calculated by inserting
the ion intensity ratios of Tables 2 and 3 into the correspond-
ing equations derived in the previous section. The calculated
deuterium PKIEs and SKIEs are given in Tables 4 and 5.
Ï
isotope effect operates on the 1-a versus a branching, the k /k8
ratio [Eq. (10)] reflects the [b-D -SKIE]Ph for H O loss from
5
1
2
O-protonated 2-phenyl-1-propanol and may be calculated
Table 4. Deuterium isotope effects in the acid-induced intramolecular
from the c ˆ [m/z 59]:[m/z 60] ratio from the etheral products
isomerization of 1-phenyl-2-propanol 1 in CH
4
at 750 Torr and 258C.
3
recovered from 2s/2b systems after correction for the
C
b
!C Migrating group Rate constant ratios
a
Isotope effects
relative concentration of the starting alcohols, that is, c[2b]/
2s]. The k /k ratio [Eq. (11)] represents the [b-D -PKIE] for
[
Ph
k
k
k
2
2
2
/k13 ˆ 1.11 Æ 0.03
/k16 ˆ 1.23 Æ 0.03
/k20 ˆ 1.06 Æ 0.04
(a-D
(b-D
(b'-D
1
-SKIE)Ph
-SKIE)Ph
3
6
1
1
the same dissociation and is derived from the following
3
-SKIE)Ph
equations: [m/z 135] ꢁ k [2s] ‡ 0.485k [2b] and [m/z 136] ꢁ
3
6
[
a]
b-H
b-H
0.5k
/k12 ˆ 1.09 Æ 0.03
.5k
1
/k14 ˆ 1.22 Æ 0.04
(b-D
(a-D
1
-PKIE)
0
.515k [2b], which were obtained from the fragmentation of
6
k
0
1
1
- SKIE)
-SKIE)
H
H
the etheral products 6, with e ˆ [m/z 135]/[m/z 136]. The [b-
[a]
1
/k15 ˆ 1.04 Æ 0.04
(b-D
1
D -SKIE] is represented by the k /k ratio [Eq. (12)], which
k1/k19 ˆ 1.08 Æ 0.04
(b'-D -SKIE)H
1
Me
4
7
3
[
[
b]
can be expressed by considering the fragments arising from
the relevant products 5. Equation (12) can be derived from
the following equations: [m/z 150] ꢁ (k ‡ ak )[2s], [m/z
k /0.5k ˆ 1.19 Æ 0.06
(b-D -PKIE)
1
5
17
2
b]
k
14/0.5k17 ˆ 1.01 Æ 0.06
2 H
(b-D -SKIE)
4
5
[a] b-H, as the spectator atom; [b] b-D, as the spectator atom.
1
51] ꢁ (k ‡ ak )[2b], [m/z 121] ꢁ (k ‡ ak )[2s] ‡ ak [2b],
7
8
4
5
8
and [m/z 122] ꢁ k [2b], with g ˆ [m/z 150]/[m/z 151], d ˆ
7
Table 5. Deuterium isotope effects in the acid-induced intramolecular
isomerization of 2-phenyl-1-propanol 2 in CH at 750 Torr and 258C.
[m/z 121]/[m/z 122], and the k /k ratio as determined above.
5 8
4
C
b
!C Migrating group Rate constant ratios Isotope effects
a
k
k
k
5
3
4
/k
/k
/k
8
6
7
ˆ [b-D
ˆ [b-D
ˆ [b-D
1
1
1
-SKIE]Ph ˆ c[2b]/[2s]
(10)
(11)
Ph
k
k
5
5
/k11 ˆ 1.12 Æ 0.02
/k
ˆ 1.17 Æ 0.02
/k10 ˆ 1.33 Æ 0.08
/k
ˆ 1.05 Æ 0.03
(a-D
(b-D
(a-D
(b-D
1
-SKIE)Ph
-SKIE)Ph
8
1
-PKIE] ˆ {(0.515e � 0.485)[2b]}/[2s]
-SKIE]Me ˆ {[g(d ‡ 1)[2b]]/
Me
k
k
4
4
1
-SKIE)Me
1
-SKIE)Me
7
[
(g ‡ 1)[2s]]} � {[(d � g)k
5
]/[(g ‡ 1)k
8
]} (12)
b-H
k /k ˆ 1.94 Æ 0.05
1
(b-D -PKIE)
(a-D -SKIE)
1 H
3
6
k
3
/k
9
ˆ 1.09 Æ 0.03
2
) The enantiomeric distribution of the ethereal products 3
from irradiation of the 2s/2a systems (Schemes 3 and 5) allows
us to evaluate the k /k ratio [Eq. (13)], which represents the
Kinetic isotope effects are determined primarily by changes
in vibrational frequencies along the reaction coordinate. It has
been generally accepted that, besides proton tunneling, PKIE
is primarily determined by the loss of zero-point energy
5
11
[
a-D -SKIE] for H O loss from O-protonated 2-phenyl-1-
1 Ph 2
propanol. Equation (13) can be derived from the following
equations: [3s] ˆ (1 � a){k [2s] ‡ 0.50k [2a]} and [3r] ˆ (1 �
5
11
(ZPE) owing to conversion of one stretching vibration in the
a)0.50k [2a], with f ˆ [3s]/[3r] ˆ [m/z 59] /[m/z 59] . The
11
S
R
reactant into the reaction coordinate. The absolute value of
PKIE is expected to be dependent on the hydrogen-transfer
symmetry and the looseness of the relevant TS structure.[
Hybridization and crowding effects determine a-SKIE,
k /k ratio [Eq. 14)] represents the [a-D -SKIE] for the same
3
9
1
H
dissociation and is derived from the following equations: [m/z
14]
1
35] ꢁ k [2s] ‡ 0.485k [2a] and [m/z 136] ꢁ 0.515k [2a],
3
9
9
which were obtained from the fragmentation of the etheral
primarily through changes in the C �H(D) out-of-plane
a
products 6, with e ˆ [m/z 135]/[m/z 136]. The [a-D -SKIE] is
1
Me
bending vibrations. The absolute value of a-SKIE increases
by increasing the TS looseness, that is, by increasing the Ca-
leaving-group bond length and by decreasing the size of the
represented by the k /k ratio [Eq. (15)], which can be
4
10
expressed by considering the fragments arising from the
relevant products 5: [m/z 150] ꢁ (k ‡ ak )[2s], [m/z 151] ꢁ
4
5
leaving moiety. The contribution of C �H(D) stretching
a
(
k ‡ ak )[2a], [m/z 121] ꢁ (k ‡ ak )[2s] ‡ k [2a] ‡ aq
1
0
11
4
5
10
vibrations to the a-SKIE value are also important. The
variation of a-SKIE from the stretching vibrations with TS
looseness is opposite to that of the bending contribution,
causing a level-off in the a-SKIE for tight TS structures.[
Hyperconjugation and relief of nonbonding interactions
determine b-SKIE, whose value depends upon the magnitude
k [2a], and [m/z 122] ꢁ a(1 � q)k [2a], with q ˆ k /(k ‡
1
1
11
14
14
k ). The q factor was calculated to be 0.458 from the k /k ˆ
1
5
14 15
[
m/z 121]/[m/z 122] ˆ 1.183 value measured by analyzing
15]
products 5 from 1b. Thus, Equation (15) can be derived from
the above equations, with g ˆ [m/z 150]/[m/z 151] and d ˆ
[
m/z 121]/[m/z 122].
of positive charge at C and the dihedral angle between the
a
[
16]
C �H(D) bond and the incipient empty p-orbital on C .
b
a
The b
�
D isotope effect on the H O loss from 2s
‡
H
with
k
k
k
5
3
4
/k11 ˆ [a-D
/k
ˆ [a-D
/k10 ˆ [a-D
1
-SKIE]Ph ˆ {0.50(f � 1)[2a]}/[2s]
-SKIE]
ˆ {(0.515e � 0.485)[2a]}/[2s]
-SKIE]Me ˆ {[g(d ‡ 1)(1 � q) � 0.5(q � 1)(g ‡ 1)][2a]}/
(13)
(14)
1
2
C !C hydrogen migration is as large as 1.94 Æ 0.05 (Ta-
b
a
9
1
H
[17]
ble 5). This value exceeds ordinary b-D -SKIE and falls in
1
the classical range of primary isotope effects for intramolec-
1
[18]
{
[d(1 � q) � (g ‡ q)][2s]} (15)
ular 1,2 hydrogen shifts (b-D -PKIE ˆ 1.5 ± 3.0). This con-
1
Chem. Eur. J. 1999, 5, No. 3
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851

M. Speranza, A. Filippi
FULL PAPER
clusion was corroborated by the accompanying modest [a-D1-
value, which corresponds to a limited development of the
SKIE] ˆ 1.09 Æ 0.03 value, which points to a rather tight TS
p-orbital vacancy at C caused by the phenyl-group partic-
H
a
‡
structure characterized by an intense H(D)�C interaction
ipation in the only partial C �OH bond cleavage. In this
a
a
2
‡
coupled with limited C �OH bond cleavage.
respect, the observed [b'-D -SKIE] < [b-D -SKIE] order is
3 Ph 1 Ph
a
2
‡
The b-D isotope effects on the H O loss from 1s with
H
suggestive of a more pronounced hyperconjugation and relief
1
2
C !C hydrogen migration amount to 1.22 Æ 0.04 and 1.19 Æ
of nonbonding interaction for the benzylic C �H(D) bonds of
b
a
b
0
.06 (Table 4), that is, in a range which may reflect either a
unsolvated 1s
‡
than for its C '�H(D) bonds. Of course, given
H
b
[
18]
[17]
small b-D -PKIE or a large b-D -SKIE. However, the
the strict similarity of the [a-D -SKIE] and [b-D -SKIE]
1
1
1 Ph 1 Ph
limited magnitude of the accompanying [b-D -SKIE] ˆ
values of Tables 4 and 5, the same conclusion applies to H O
2
1
H
1
.04Æ 0.04, 1.01Æ 0.06, [b'-D -SKIE] ˆ 1.08Æ 0.04, and [a-D -
loss from 2sH
‡
with C !C Ph migration.
3
H
1
b
a
SKIE] ˆ 1.09 Æ 0.03, the latter coinciding with that measured
The a-D isotope effect on H O loss from 2s
‡
with C !C
H
1
2
H
b
a
in the H O loss from 2s
‡
(Table 5), speaks in favor of the first
Me migration is large (1.33 Æ 0.08; Table 5), relative to the a-
2
H
hypothesis involving anchimeric assistance by the b hydrogen
D effect when the participating groups are hydrogen (1.09 Æ
1
via a TS structure, characterized by significant H(D)�C
0.03) or phenyl (1.12 Æ 0.02). This observation, coupled with
a
‡
bonding and limited C �OH bond cleavage. The low [b-
the reduced b-D ˆ 1.05 Æ 0.03 (Table 5), points to methyl-
a
2
1
D -PKIE] ˆ 1.22 Æ 0.04 and [b-D -PKIE] ˆ 1.19 Æ 0.06 values,
group-assisted H O loss from 2s
‡
proceeding through a TS
1
2
2
H
compared with that measured for the H O loss from 2s
‡
structure characterized by an advanced Me�C bonding
2
H
a
‡
[22]
(
1.94 Æ 0.05; Table 5), are indicative of the operation of both
coupled with extensive C �OH bond cleavage. The above
a
2
C �H(D) stretching and bending vibrations in the TS
conclusions about the nature of the TS structures involved in
the competing anchimeric assistance of H O loss from 1s
b
structure of the intramolecular nonlinear C ´´´ H(D) ´ ´´ C
‡
H
b
a
2
[
14b, 19]
transfer.
Since the C �H stretching frequency should be
and 2sH
‡
find further support from the comparative analysis of
b
[20]
[1]
reduced more by deuteration than a bending mode, the
the relevant activation parameters, reported in Figure 1.
‡
2
comparatively small [b-D -PKIE] on the H O loss from 1s
‡
Early TS structures, characterized by a partial C �OH
1
2
H
a
(
Table 4) suggests a greater weight of C �H(D) bendings in its
bond cleavage coupled with a weak Ph�C interaction, are
b
a
TS structure than in that of the corresponding process in 2s
‡
fully consistent with the relatively large A and E* values
H
Ph
Ph
[
21]
(Table 5).
measured for H O loss from 1s
‡
H
and 2sH . In these flexible
‡
2
In the gas phase, the a-D isotope effect on H O loss from
TS structures, the charge is essentially distributed over the
1
2
1
sH
‡
with C !C phenyl-group migration amounts to 1.11 Æ
C �O atoms and the Ph�C rotor is only partially restrained.
b
a
a
b
0.03 (Table 4), a value which is in agreement with those
In contrast, the small A and E* values, governing the
H H
measured in the aryl-group-assisted solvolysis of 1-aryl-2-
alkyl tosylates in the condensed phase. However, this gas-
competing b-hydrogen participation, conform to a rigid TS
[
8a]
structure, characterized by significant H(D)�C bonding and
a
‡
phase isotope effect is accompanied by a sizable b-D (ˆ
limited C �OH bond cleavage. Here, the positive charge is
1
a
2
1
.13 Æ 0.03) and a limited b'-D (ˆ1.06 Æ 0.04) isotope effect
transferred essentially to the benzylic moiety, with consequent
3
(Table 4). This pair of values is inconsistent with the
quenching of the Ph�C rotor. The intermediate A and EM*e
b
Me
corresponding pairs measured in both the aryl-group-assisted
values, associated to b-methyl participation in the H O loss
2
solvolysis of 1-(p-anisyl)-2-propyl tosylate ([b-D -SKIE] ˆ
from 2sH , can be well-accounted for by a borderline TS
‡
1
0
1
.998; [b'-D -SKIE] ˆ 1.123) and the unassisted solvolysis of
structure, in which intense Me�C bonding is now coupled
3
a
‡
-phenyl-2-propyl tosylate ([b-D -SKIE] ˆ 1.295; [b'-D -
with more extensive C �OH bond cleavage.
1
3
a
2
[
8a]
SKIE] ˆ 1.242). This apparent contradiction can be solved
by considering the stereochemistry of the aryl-group partic-
ipation in the corresponding systems. In the condensed phase,
solvation and ion-pairing factors induce a backside interaction
Conclusions
between the aryl group and the C �OTs. In contrast, in the gas
a) This paper presents a combined pattern of b-D -PKIE, a-
1
D -SKIE, b-D -SKIE, and b'-D -SKIE as the only unequiv-
1 1 3
ocal mechanistic criterion for the TS structures of the gas-
a
Ï
phase the H O loss from 1s
‡
involves both a backside
2
H
(
major) and a frontside (minor) phenyl-group participation.[1]
Therefore, the gas-phase b-D ˆ 1.23 Æ 0.03 and b'-D ˆ
phase H O loss from O-protonated (S)-1-phenyl-2-propanol
1
3
2
1
.06 Æ 0.04 values reflect a convolution of b-D effects for
(1sH
‡
) and O-protonated (S)-2-phenyl-1-propanols (2sH
‡
).
back
Ph
both the backside ([b-D -SKIE]
ꢂ 1) and the frontside
[17]
b) While the measured gas-phase b-D -PKIE, a-D -SKIE,
1
1
1
Ï
front
Ph
phenyl-group participation ([b-D -SKIE]
 1.4), whose
and b'-D -SKIE values fall in the classical range of deuterium
1
3
TS structures involve different charge location at C and
effects for analogous solvolytic processes, the relatively large
a
different dihedral angles between the C �H(D) bond and the
[b-D -SKIE] 's are accounted for by partitioning between
b
1
Ph
[
16, 17]
incipient empty p-orbital on C (Scheme 1).
Therefore,
backside and frontside phenyl-group participation to the
process. This fact warns against thoughtless correlations of the
observed isotope effects to a single TS structure.
a
despite its large value for the solution chemistry standards, the
gas-phase [b-D -SKIE] ˆ 1.23 Æ 0.03 is interpreted in terms
1
Ph
of backside and frontside phenyl-group-assisted H O losses
c) Discussion of the measured deuterium PKIEs and SKIEs
2
Ï
from different conformers of 1sH
‡
, via early TS structures with
in the light of the relevant activation parameters provides
conclusive insights into the TS structures governing gas-phase
‡
a weak Ph�C interaction coupled with a partial C �OH
a
a
2
bond cleavage (a-D -SKIE] ˆ 1.11 Æ 0.03). This conclusion is
anchimeric assistance to H O loss from 1s and 2sH
‡
‡
by all
1
2
H
in agreement with the small gas-phase b'-D ˆ 1.06 Æ 0.04
the groups adjacent to the reaction center. Thus, an early TS
3
8
52
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Wagner ± Meerwein Rearrangements
845±853
structure is involved in the phenyl-group assistance, charac-
[9] H. C. Brown, G. Zweifel, J. Am. Chem. Soc. 1960, 82, 4708.
[10] D. Achet, D. Rocrelle, I. Murengezi, M. Delmas, A. Gaset, Synthesis
986, 643.
‡
terized by partial C �OH bond cleavage coupled with a
a
2
1
weak Ph�C interaction. In contrast, b-hydrogen participation
a
[
11] a) P. Ausloos, S. G. Lias, R. Gorden, Jr., J. Chem. Phys. 1963, 39, 3341;
b) P. Ausloos, Ion-Molecule Reactions (Ed.: J. L. Franklin), Plenum,
New York, 1970; c) P. Ausloos, S. G. Lias, J. Chem. Phys. 1962, 36,
involves a much tighter TS structure, characterized by
‡
significant H(D)�Ca bonding and limited C �OH bond
a
2
3
163; d) S. G. Lias, P. Ausloos, J. Chem. Phys. 1962, 37, 877.
cleavage. Finally, b-methyl group participation in 2s
‡
in-
H
[
12] Neutralization of the O-protonated ethers, arising from addition of
volves a borderline TS structure, in which intense Me�C
a
‡
isomeric [C
9
H
11 ] to methanol, may proceed through several path-
‡
bonding is coupled with a pronounced C �OH bond
a
2
ways, including proton transfer to the substrate itself, to the walls of
the reaction vessel, or to adventitious bases that are either initially
added to the gaseous mixture or formed by its radiolysis.
elongation.
d) It is a generally accepted view[5, 16a] that neighboring-group
Ï
[
13] According to Schemes 2 and 7, [m/z 150] ꢁ k
15)[1b], [m/z 121] ꢁ k [1s] ‡ k14[1b], and [m/z 122] ꢁ k15[1b]. From
these relations, 0.5k
/k14 ˆ {0.5g(1 ‡ d)[1b]}/{(d � g)[1s]} and 0.5k
15 ˆ {0.5g(1 ‡ d)[1b]}/{(1 ‡ g)[1s]}, with g ˆ [m/z 150]/[m/z 151] and
d ˆ [m/z 121]/[m/z 122]. Using the g ˆ 1.46 and d ˆ 2.96 values of
Table 2, measured for products 5 from the 1s/1b* systems, 0.5k
.01 and 0.5k
1
[1s], [m/z 151] ꢁ (k14 ‡
participation in ionic processes is enhanced as the nucleophi-
licity and the dielectricity of the reaction medium decrease.
Accordingly, the results of the present and the preceding[
k
1
1
1
/
1]
k
papers demonstrate that gas-phase solvolysis of 1sH
‡
and 2sH
‡
1
/k14
ˆ
involves unsubstituted phenyl-group anchimeric assistance (a
kD process), whereas the analogous acetolysis of 1-phenyl-2-
2
1
/k15 ˆ 1.23. These phenomenological values reflect three
different factors, namely: i) the relative population of active con-
formers of O-protonated 1-phenyl-2-propanol (Scheme 1) involved in
ethyl tosylate proceeds through competing solvent- (a k
S
[8b]
process) and anchimeric-assisted (k ) mechanisms,
and
the H/D anchimeric assistance to H O loss; ii) the activation
D
2
that of 1-phenyl-2-propyl tosylate by predominant anchimer-
parameters governing hydrogen-atom anchimeric assistance in each
conformer; iii) the isotope effect on these activation parameters.
Indeed, the above values significantly diverge from those derived from
ic- and solvent-unassisted unimolecular dissociation (a k
C
[
8a]
process).
the rac-1/1b systems, that is 0.5k
where no differences in factors i) and ii) are present and, therefore, the
only rate difference is due to factor iii).
1
/k14 ˆ 1.22 and 0.5k /k15 ˆ 1.04,
1
[
[
[
14] a) S. S. Glad, F. Jensen, J. Am. Chem. Soc. 1994, 116, 9302, and
Acknowledgements
references therein; b) X. Duan, S. Scheiner, J. Am. Chem. Soc. 1992,
1
14, 5849.
This research was supported by the Italian Ministero dellꢁUniversit aÁ e della
Ricerca Scientifica e Tecnologica (MURST) and by the Italian National
Research Council (CNR). We thank Anna Troiani for help with some of the
early experimental work.
15] a) S. S. Glad, F. Jensen, J. Am. Chem. Soc. 1997, 119, 227, and
references therein; b) K. C. Westaway, T. V. Pham, Y. Fang, J. Am.
Chem. Soc. 1997, 119, 3670, and references therein.
16] a) S. E. Scheppele, Chem. Rev. 1972, 72, 511, and references therein;
b) D. J. DeFrees, M. Taagepera, B. A. Levi, S. K. Pollack, K. D.
Summerhays, R. W. Taft, M. Wolfsberg, W. J. Hehre, J. Am. Chem.
Soc. 1979, 101, 5532.
[
1] A. Filippi, M. Speranza, Chem. Eur. J. 1999, 5, 834 ± 844.
[
2] a) D. J. Cram, J. Am. Chem. Soc. 1949, 71, 3863; b) D. J. Cram, R.
Davis, J. Am. Chem. Soc. 1949, 71, 3875; c) D. J. Cram, J. Am. Chem.
Soc. 1964, 86, 3767; d) C. J. Lancelot, D. J. Cram, P. von R. Schleyer,
Carbonium Ions, Vol. III (Eds.: G. A. Olah, P. von R. Schleyer) Wiley,
New York, 1972, chapter 27; e) S. Winstein, B. K. Morse, E. Grunwald,
K. C. Schreiber, J. Corse, J. Am. Chem. Soc. 1952, 74, 1113.
[17] For an S
from 1.31 to 0.99 as the dihedral angle between the C
the incipient p-orbital at C is varied from 180(0) to 908 (V. J.
Shiner, Jr., J. S. Humphrey, Jr., J. Am. Chem. Soc. 1963, 85, 2416). The
b-D -SKIE on the ethanolysis of cis-4-tert-butylcyclohexyl brosylate
N
1 reaction on tertiary chlorides in solution, b-D
1
-SKIE varies
�
H(D) bond and
b
a
1
amounts to 1.436, when the b-D is axial, and to 1.096, when the b-D is
equatorial (V. J. Shiner, Jr., J. G. Jewett, Jr., J. Am. Chem. Soc. 1965,
87, 1382).
[
3] a) H. C. Brown, The Transition State, Special Publ. No. 16, The
Chemical Society, London, 1962, p. 149; b) H. C. Brown, K. J. Morgan,
F. J. Cloupek, J. Am. Chem. Soc. 1965, 87, 2137.
[18] J. L. Fry, G. J. Karabatsos, Carbonium Ions (Eds.: G. A. Olah,
P. von R. Schleyer) Wiley, New York, 1970, p. 526. See also: a) F.
Cacace, M. E. Crestoni, S. Fornarini, J. Am. Chem. Soc. 1992, 114,
6776; b) M. E. Crestoni, S. Fornarini, M. Lentini, M. Speranza, J. Phys.
Chem. 1996, 100, 8285.
[19] M. F. Hawthorne, E S. Lewis, J. Am. Chem. Soc. 1958, 80, 4296.
[20] D. Liotta, M. Saindane, L. Waykole, J. Stephens, J. Grossman, J. Am.
Chem. Soc. 1988, 110, 2667.
[
4] a) H. C. Brown, R. Bernheimer, C. J. Kim, S. E. Scheppele, J. Am.
Chem. Soc. 1967, 89, 370; b) H. C. Brown, C. J. Kim, J. Am. Chem. Soc.
1968, 90, 2080; c) W. H. Saunders Jr., S. Asperger, D. H. Edison, J. Am.
Chem. Soc. 1958, 80, 2421; d) S. L. Loukas, M. R. Velkou, G. A.
Gregoriou, J. Chem. Soc. Chem. Commun. 1969, 1199; e) S. L. Loukas,
F. S. Varveri, M. R. Velkou, G. A. Gregoriou, Tetrahedron Lett. 1971,
1803.
[
[
5] B. Capon, S. P. McManus, Neighboring Group Participation Vol. 1,
Plenum, New York, 1976.
6] a) D. E. Sunko, S. Borcic, Isotope Effects in Chemical Reactions (Eds.:
C. J. Collins, N. S. Bowman), Van Nostrand Reinhold, New York, 1970,
chapter 3; b) V. J. Shiner, Jr., Isotope Effects in Chemical Reactions
[21] An alternative rationale can be found in some minor contribution of
tunneling in the more strained TS structure of the b-hydrogen
2
participation in H O loss from O-protonated 2-phenyl-1-propanol
relative to the that of the same process in O-protonated 1-phenyl-2-
propanol (see ref. [14b]). Strain is expected to be higher in the first TS
(
1
Eds.: C. J. Collins, N. S. Bowman), Van Nostrand Reinhold, New York,
970, chapter 2; c) S. E. Scheppele, Chem. Rev. 1972, 72, 511.
structure than in the latter one on account of the more intense
‡
H(D)
tion.
[22] The low [b-D
ing [b-D -SKIE]Ph, may not only reflect later TS structures, but also a
less extensive frontside participation.
�
Ca interaction required for the same C �OH2 bond elonga-
a
[
[
7] a) W. H. Saunders, Jr., R. Glaser, J. Am. Chem. Soc. 1960, 82, 3586;
b) D. J. Cram, J. Tadanier, J. Am. Chem. Soc. 1959, 81, 2737; c) C. C.
Lee, L. Noszko, Can. J. Chem. 1966, 44, 2491.
1
1 H
-SKIE]Me and [b-D -SKIE] , relative to the correspond-
1
8] a) K. Funatsu, M. Fujio, Y. Tsuno, Mem. Fac. Sci. Kyushu Univ. Ser. C
1981, 13, 125; b) K. Funatsu, M. Kimura, T. Furukama, M. Fujio, Y.
Tsuno, Mem. Fac. Sci. Kyushu Univ. Ser. C 1984, 14, 343.
Received: June 16, 1998 [F1212]
Chem. Eur. J. 1999, 5, No. 3
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