Solvent-equilibrated homoadamantyl chloride ion pairs from chloroformate or oxachlorocarbene fragmentations

Article abstract of DOI:10.1021/ol040055w

(Chemical Equation Presented) Fragmentations of 3-homoadamantyl chloroformate and 3-homoadamantyloxychlorocarbene produce identical ion pairs as product-determining intermediates.

Full text of DOI:10.1021/ol040055w

ORGANIC
LETTERS
2
004
Vol. 6, No. 23
293-4296
Solvent-Equilibrated Homoadamantyl
Chloride Ion Pairs from Chloroformate
or Oxachlorocarbene Fragmentations
4
Robert A. Moss,* Jingzhi Tian, and Ronald R. Sauers*
Department of Chemistry and Chemical Biology, Rutgers,
The State UniVersity of New Jersey, New Brunswick, New Jersey 08903
moss@rutchem.rutgers.edu
Received September 10, 2004
ABSTRACT
Fragmentations of 3-homoadamantyl chloroformate and 3-homoadamantyloxychlorocarbene produce identical ion pairs as product-determining
intermediates.
Kevill, Kyong, et al. present strong evidence that the
fragmentation of 1-adamantyl chloroformate (1) in hydroxylic
solvents proceeds with loss of carbon dioxide to adamantyl
chloride ion pairs, which then give adamantyl chloride (1-
AdCl) by ion pair collapse or 1-AdOS by solvolysis; cf.
Scheme 1.1 This process closely resembles the fragmenta-
by ion pair return or 1-AdOMe by ion pair solvolysis; cf.
Scheme 2.
3
,4
Scheme 2
,2
Scheme 1
Despite the overall similarities, the ion pairs of Schemes
and 2 are not identical: Kevill notes that the [1-AdOMe]/
1
[
1-AdCl] product ratio from the fragmentation of chlorofor-
2
mate 1 in methanol is 2.9, whereas this ratio is only 0.67
3b
+
-
from carbene 2. The [1-Ad Cl ] ion pair from the carbene
is more likely to undergo chloride return, while the ion pair
from the chloroformate prefers solvolysis to 1-AdOMe.
Either a higher-energy, shorter-lived carbocation forms from
carbene 2, or there is less steric hindrance to chloride return
tion of 1-adamantyloxychlorocarbene (2) in (for example)
methanol, where an analogous ion pair, there formed with
the expulsion of carbon monoxide, similarly affords 1-AdCl
when CO, rather than CO
2
, is the ejected molecule.2
Moreover, it is likely that one or both of the ion pairs of
Schemes 1 and 2 are not solvent- and anion-equilibrated
and therefore exhibit precursor “memory” and different
(
1) Kevill, D. N.; Kyong, J. B.; Weitl, F. L. J. Org. Chem. 1990, 55,
4
304.
(
(
2) Kyong, J. B.; Yoo, J.-S.; Kevill, D. N. J. Org. Chem. 2003, 68, 3425.
3) (a) Moss, R. A.; Ge, C.-S.; Maksimovic, L. J. Am. Chem. Soc. 1996,
1
18, 9792. (b) Moss, R. A.; Zheng, F.; Fed e´ , J.-M.; Sauers, R. R. Org.
(4) Moss, R. A.; Zheng, F.; Fed e´ , J.-M.; Johnson, L. A.; Sauers, R. R.
J. Am. Chem. Soc. 2004, 126, 12421.
Lett. 2002, 4, 2341.
1
0.1021/ol040055w CCC: $27.50
© 2004 American Chemical Society
Published on Web 10/20/2004

4
+
product distributions. We recently reported that the [1-Ad -
-
Cl ] ion pairs generated in methanol by the direct fragmenta-
tion of carbene 2 or the ring expansion-fragmentation of
3
-noradamantylmethoxychlorocarbene (3) lead to divergent
3
b,4
[1-AdOMe]/[1-AdCl] product ratios; cf. Scheme 3. The
7
3
-Homoadamantanol was converted in 79% yield to the
Scheme 3
8
corresponding chloroformate (8) with triphosgene and
pyridine in ether/benzene. The chloroformate was character-
1
13
ized by H and C NMR spectroscopy, as well as by IR
spectroscopy (see Supporting Information). Similarly, 1-ada-
1
,9
mantyl chloroformate was prepared from 1-adamantanol
using triphosgene in place of phosgene.
The decomposition of 8 (to 3-HomoadCl) in benzene at
15 °C was monitored by IR spectroscopy relative to an ethyl
acetate standard, measuring the integrated intensity of the
-
1
chloroformate’s carbonyl absorbance (1776 cm ) against
that of EtOAc (1739 cm ) at 5-10 min intervals; cf. Figure
S1 in Supporting Information. From a correlation of ln-
ratio was ∼0.43 from carbene 3 but 0.67 from carbene 2. In
-1
+
-
our view, the [1-Ad Cl ] ion pair is not sufficiently stable
to live long enough to achieve anion and solvent cage
equilibration and to “forget” its precursor, whether that be
chloroformate 1 or carbenes 2 or 3.
-
1
(
2
relative intensity at 1776 cm ) vs time, we obtained k )
-
4
-1
.56 × 10
s
for the decay of 8 (Figure S2, Supporting
Information), corresponding to a half-life of ∼45 min. The
decomposition of 8 is therefore 465 times faster than the
analogous reaction of its 1-adamantyl relative (k ) 5.51 ×
However, the 3-homoadamantyl (3-Homoad) cation (4) is
∼
4 kcal/mol more stable than the 1-adamantyl cation (5) in
5
,6
+
-
the gas phase. If the solution lifetimes of the [R Cl ] ion
-
7
-1
9
1
0
s
in benzene at 14.6 °C). This is reasonable, given
+
+
-
pairs parallel the stabilities of R , then [3-Homoad Cl ]
will be longer-lived than [1-Ad Cl ] and could achieve
solvent equilibration and precursor independence. Indeed,
5
that the fragmentation of 8 transits the more stabilized
homoadamantyl cation.
+
-
Fragmentations of chloroformates 1 and 8 were carried
out in MeOH-DCE mixtures at 20 °C. The fragmentation
of 1 was followed by IR, monitoring the decrease in carbonyl
+
-
[3-Homoad Cl ] ion pairs generated either by direct frag-
mentation of carbene 6 or by ring expansion-fragmentation
of 1-adamantylmethoxychlorocarbene (7) exhibit identical
-1
absorption at 1783 cm over 3 days. With the more reactive
, fragmentation was complete in 2 h. In each case, the major
-
partition between Cl return and MeOH solvolysis across a
8
broad range of methanol concentrations in dichloroethane
products were RCl and ROMe, readily identified by capillary
GC and GC-MS comparisons with authentic materials (see
Supporting Information). The chlorides and ethers can be
(
DCE); in pure methanol, the [3-HomoadCl]/[3-Homo-
4
adOMe] distribution is ∼0.71 from either source. We
estimate that 20-30 ps is required for solvent and anion
+
-
attributed to collapse or methanolysis of [R Cl ] ion pairs
see, for example Scheme 1). These products were ac-
companied by minor quantities of 1-AdOH (2-3.5% from
) or 3-HomoadOH (4-8% from 8), which may have arisen
by adventitious hydrolysis of the chloroformates (followed
by loss of CO ).
+
-
4
equilibration of the [3-Homoad Cl ] ion pairs.
(
1
2
Tables S1 and S2 (Supporting Information) detail the
capillary GC product distributions from the fragmentations
of 1 and 8 at each of 7 MeOH mole fractions in DCE. Ratios
of [ROMe]/[RCl] were determined from the product distribu-
tions and corrected for relative detector response. In the case
of chloroformate 8, traces of 3-HomoadCl formed during
These results clearly predict that, in contrast to the
-
+
-
divergent Cl /MeOH selectivities of the [1-Ad Cl ] ion pairs
from chloroformate 1 and carbene 2, the selectivities
associated with the ion pairs formed from 3-homoadamantyl
chloroformate (8) and 3-HomoadOCCl (6) should be identi-
cal. Here we present an experimental test of this proposition,
as well as related computational studies of the relevant ion
pairs.
1
preparation and manipulation. H NMR analysis permitted
the quantitation of this “preexisting” chloride so that the
fragmentation product mixture could be corrected for it by
1
0
subtraction from the chloride component.
Figure 1 illustrates the dependence of the [1-AdOMe]/[1-
AdCl] product ratio from the fragmentation of chloroformate
(
5) (a) Abboud, J.-L. M.; Alkorta, I.; Davalos, J. Z.; M u¨ ller, P.;
Quintanilla, E.; Rossier, J.-C. J. Org. Chem. 2003, 68, 3786. (b) Abboud,
J.-L. M.; Herreros, M.; Notario, R.; Lomas, J. S.; Mareda, J.; M u¨ ller, P.;
Rossier, J.-C. J. Org. Chem. 1999, 64, 6401. (c) Abboud, J.-L. M.; Alkorta,
I.; Davalos, J. Z.; M u¨ ller, P.; Quintanilla, E. AdV. Phys. Org. Chem. 2002,
(7) Farcasiu, D.; J a¨ hme, J.; R u¨ chardt, C. J. Am. Chem. Soc. 1985, 107,
5717.
(8) Gerzon, K.; Krumkalns, E. V. U.S. Patent 3,369,041, 1968.
(9) Kevill, D. N.; Weitl, F. L. J. Am. Chem. Soc. 1968, 90, 6416.
(10) Control experiment established that 3-HomoadCl was not solvolyzed
to 3-HomoadOMe after 12 h in MeOH at 25 °C.
3
7, 57.
6) This corresponds to the free energy difference associated with chloride
(
+
+
exchange between 1-Ad and 3-Homoad in the gas phase and reflects the
intrinsic gas-phase stabilities of the carbocations.
4294
Org. Lett., Vol. 6, No. 23, 2004

Figure 1. Product ratio [1-AdOMe]/[1-AdCl] from fragmentations
of chloroformate 1 (Scheme 1) and carbene 2 (Scheme 2) in MeOH/
DCE vs øMeoH; cf. Table S1 in Supporting Information (for 1) and
Table S4 in Supporting Information of ref 4 (for 2). Key: 9 from
chloroformate 1; b from carbene 2.
Figure 2. Product ratio [3-HomoadOMe]/[3-HomoadCl] from the
fragmentations of chloroformate 8 and carbene 6 (see Scheme 4)
in MeOH/DCE vs øMeOH; cf. Table S2 in Supporting Information
(for 8) and Table S6 in Supporting Information of ref 4 (for 6).
Key: 9 from chloroformate 8; b from carbene 6.
1
on the mole fraction of MeOH in DCE. This correlation is
Computational studies were carried out for the fragmenta-
tions of chloroformates 1 and 8. All structures were fully
optimized by analytical gradient methods using the Gaus-
compared with analogous data for the fragmentation of
4
1-adamantyloxychlorocarbene (2). The dependences of the
ether/chloride product ratios on øMeOH are clearly very dif-
ferent. Chloride return dominates the carbene fragmentation,
whereas methanolysis holds sway over the chloroformate
decomposition. The detailed studies summarized in Figure
1
11a
sian98 and Gaussian03 suites and density functional (DFT)
calculations at the 6-31G(d) level, with the exchange
1
1a,b
potentials of Becke
Yang, and Parr.
and the correlation functional of Lee,
Activation energies were corrected for
1
1a,c
2
underscore Kevill’s conclusion that the fragmentations of
zero-point energy differences (ZPVE, unscaled) and thermal
effects at 298.150 K. Vibrational analyses established the
nature of stationary points as either energy minima (no
imaginary frequencies) or first-order saddle points (one
imaginary frequency). Solvation simulations used the polar-
ized continuum model (PCM) methodology.
The transition state (TS) computed for the fragmentation
of chloroformate 1 (Figure S3a in Supporting Information;
1
and 2 do not transit identical ion pair intermediates. The
+
-
results are consistent with our suggestion that [1-Ad Cl ]
ion pairs are too short-lived to achieve the anion and solvent
cage equilibration required for precursor independence.
4
Figure 2 compares the dependences of the [3-Homo-
adOMe]/[3-HomoadCl] product ratios from the fragmenta-
tions of chloroformate 8 and carbene 6 on øMeOH in MeOH-
DCE solutions. Within experimental error ((0.04), the
product ratios for the two reactions are very similar across
the entire range of methanol mole fractions and effectively
independent of the precursor, chloroformate 8 or carbene 6.
The results have two important consequences: they provide
strong support for Kevill’s formulation of tertiary-alkyl
chloroformate decomposition as an ion pair process and
they bolster our previous contention that the fragmentation
of homoadamantyloxychlorocarbene (6), but not that of
adamantyloxychlorocarbene (2), occurs via a counterion- and
solvent-equilibrated ion pair as the product-determining
1
1a
∆
H* (298 K) ) 26.9 kcal/mol in vacuo) was subjected to
an intrinsic reaction coordinate (IRC) calculation, followed
Scheme 4
1
,2
4
intermediate.
Scheme 4 summarizes the key result: both chloroformate
+
-
8
and carbene 6 fragment to [3-Homoad Cl ] ion pair 9,
which either collapses to chloride 10 or is diverted by
methanol to ether 11. The same ion pair is formed from either
precursor, so that the product ratio [11]/[10] is precursor-
independent.
Org. Lett., Vol. 6, No. 23, 2004
4295

by PCM optimization in simulated methanol, affording the
ion pair depicted in Figure 3a. Similarly, fragmentation of
chloroformate 8 was computed to traverse the TS shown in
Figure S3b (Supporting Information, ∆H* ) 21.4 kcal/mol
in vacuo). An IRC calculation and optimization in methanol
yielded the ion pair shown in Figure 3b. The lower activation
enthalpy calculated for the 3-Homoad chloroformate vs 1-Ad
chloroformate reflects the 4 kcal/mol greater stability of
+
+
5,6
3
-Homoad vs 1-Ad in the gas phase at 331 K.
The chloroformate-derived ion pairs of Figure 3 can be
compared with the corresponding ion pairs computed for the
fragmentations of carbenes 2 and 6 (Figures 6 and 5 in ref
4). All four ion pairs are similar and feature H-bonding
between the chloride anion and the C-H bonds that flank
+
-
the cationic carbon atom. In the [1-Ad Cl ] case, the C-H‚
-
‚
‚Cl separations are 2.71 Å from chloroformate 1 and 2.80
4
+
-
Å from carbene 2, while the accompanying C ‚‚‚Cl
separations are 4.10 and 4.28 Å, respectively, all in simulated
methanol. For the [3-Homoad Cl ] ion pairs, the C-H‚‚‚
Cl separations are 2.38 and 2.82 Å from chloroformate 8
and 2.54 and 2.90 Å from carbene 6. The related C ‚‚‚Cl
Figure 3. (a) Optimized ion pair from the fragmentation of
chloroformate 1 from an IRC calculation on the TS shown in Figure
S3a (Supporting Information) using B3LYP/6-31G(d) in simulated
methanol with the PCM.11 (b) Optimized ion pair from the
fragmentation of chloroformate 8 from an IRC calculation on the
TS shown in Figure S3b using B3LYP/6-31G(d) in simulated
+
-
-
+
-
separations are 3.86 and 4.16 Å, respectively.
The computed ion pairs are not identical in either case,
11
methanol (PCM).
-
although the experimentally observed MeOH/Cl selectivity
+
-
is comparable in the [3-Homoad Cl ] reactions (Scheme 4).
The residual differences in the computed ion pair geometries
precursors) as opposed to CO (from the carbene precursors).
We also note that the PCM method used to optimize the ion
pairs in methanol does not employ actual solvent molecules
and cannot replicate methanol-chloride H-bonds. However,
the computational study strongly supports ion pairs as the
product-determining intermediates in the fragmentations of
chloroformates 1 and 8 (and carbenes 2 and 6). Furthermore,
experiment demonstrates that the ion pairs derived from
2
may reflect the presence of CO (from the chloroformate
(11) (a) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
Robb, M. A.; Cheeseman, J. R.; Zakrzewski, V. G.; Montgomery, J. A.,
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M.; Replogle, E. S.; Pople, J. A. Gaussian 98, revision A.9; Gaussian,
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Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.;
Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda,
R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai,
H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Adamo,
C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A.
J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.;
Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich,
S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A.
D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A.
G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.;
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Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian
3-homoadamantyl chloroformate and 3-homoadamantyloxy-
chlorocarbene behave as solvent- and anion-equilibrated
species in methanolic solution, in keeping with predictions
4
based on previous results.
Acknowledgment. We are grateful to the National
Science Foundation for financial support and to the National
Center for Supercomputing Applications for allocation of
computer time on the IBM pseries 690 (Grant CHE 030060).
We thank Professor Dennis N. Kevill for helpful cor-
respondence.
Supporting Information Available: Synthetic proce-
dures, Tables S1 and S2 of product distributions for
chloroformates 1 and 8, and Figures S1-S3. This material
is available free of charge via the Internet at http://pubs.acs.org.
0
3, revision B.02; Gaussian, Inc.: Pittsburgh, PA, 2003. (b) Becke, A. D.
J. Chem. Phys. 1993, 98, 5648. (c) Lee, C.; Yang, W.; Parr, R. G. Phys.
ReV. B 1988, 37, 785.
OL040055W
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Org. Lett., Vol. 6, No. 23, 2004