Carbenoid chain reactions: Substitutions by organolithium compounds at unactivated 1-chloro-1-alkenes

Article abstract of DOI:10.1021/ja0649116

The deceptively simple "cross-coupling" reactions Alk ₂C=CA-Cl + RLi → Alk₂C=CA-R + LiCl (A = H, D, or Cl) occur via an alkylidenecarbenoid chain mechanism in three steps without a transition metal catalyst. In the initiating step 1,

Full text of DOI:10.1021/ja0649116

Published on Web 10/27/2006
Carbenoid Chain Reactions: Substitutions by Organolithium
Compounds at Unactivated 1-Chloro-1-alkenes†
Rudolf Knorr,* Claudio Pires, Claudia Behringer, Thomas Menke,
Johannes Freudenreich, Eva C. Rossmann, and Petra Bo¨hrer
Contribution from the Department of Chemistry and Biochemistry,
Ludwig-Maximilians-UniVersita¨t, Butenandtstr. 5-13, 81377 Mu¨nchen, Germany
Received July 11, 2006; E-mail: rhk@cup.uni-muenchen.de
Abstract: The deceptively simple “cross-coupling” reactions Alk2CdCA-Cl + RLi f Alk2CdCA-R + LiCl
(A ) H, D, or Cl) occur via an alkylidenecarbenoid chain mechanism in three steps without a transition
metal catalyst. In the initiating step 1, the sterically shielded 2-(chloromethylidene)-1,1,3,3-tetramethylindans
2a-c (Alk2CdCA-Cl) generate a Cl,Li-alkylidenecarbenoid (Alk2CdCLi-Cl, 6) through the transfer of atom
A to RLi (methyllithium, n-butyllithium, or aryllithium). The chain cycle consists of the following two steps:
(i) A fast vinylic substitution reaction of these RLi at carbenoid 6 (step 2) with formation of the chain carrier
Alk2CdCLi-R (8), and (ii) a rate-limiting transfer of atom A (step 3) from reagent 2 to the chain carrier 8
with formation of the product Alk2CdCA-R (4) and with regeneration of carbenoid 6. This chain propagation
step 3 was sufficiently slow to allow steady-state concentrations of Alk2CdCLi-Aryl to be observed (by
NMR) with RLi ) C6H5Li (in Et2O) and with 4-(Me3Si)C6H4Li (in t-BuOMe), whereas these chain processes
were much faster in THF solution. PhCtCLi cannot perform step 1, but its carbenoid chain processes with
reagents 2a and 2c may be started with MeLi, whereafter LiCtCPh reacts faster than MeLi in the product-
determining step 2 to generate the chain carrier Alk2CdCLi-CtCPh (8g), which completes its chain cycle
through the slower step 3. The sterically congested products were formed with surprising ease even with
RLi as bulky as 2,6-dimethylphenyllithium and 2,4,6-tri-tert-butylphenyllithium.
Introduction
features of a stabilized carbanion (if A ) chlorine or R ) aryl)
and a well-built radical. All four of these mechanistic possibili-
The 2-(chloromethylidene)-1,1,3,3-tetramethylindans (2) are
sterically shielded examples of unactivated, terminal 1-chloro-
1-alkenes. Because they do not carry electron-withdrawing
substituents at the C2 side of the C2CR double bond, they should
be very reluctant1,2 to incorporate nucleophiles at CR with
formation of the intermediate 1 of the addition-rotation-
elimination mechanism (ARE)3 of nucleophilic vinylic substitu-
tion, because C2 of 1 would then have to accommodate negative
charge between tert-alkyl groups, with poor chances of stabi-
lization by solvation in this sterically congested environment.
Yet surprisingly, we obtained the substitution products 4d-p
with gratifying ease when reacting 2a-c in suitable ethereal
solvents with organolithium reagents (RLi), whereas unsatisfac-
tory results were found with some of the approved methods of
such cross-coupling using transition metal catalysts, as specified
in section 4. A vinylic SN1 mechanism via an unstabilized
carbenium intermediate 3 to give 4 appears improbable for the
reagents 2. Because some RLi compounds are potent reductants,
an electron-transfer process (ET) might precede the radical cage
recombination 5 f 7 f 4 or initiate the SRN1 radical chain
mechanism 5 f 7 f 9 f 4, where intermediate 9 combines
ties predict a 1:1 stoichiometry of RLi and 2, in keeping with
most of the cases investigated below. But perusal of the
literature4a suggested that an alkylidenecarbenoid5,6 6 should
be generated from 2 with RLi and might then be attacked by a
second molar equivalent of RLi with formation of the alkenyl-
lithium product 8 rather than 4. However, both the verification
of the 1:2 stoichiometry to be expected in this case and the
interception of 8 by carboxylation with CO2 to give 10 were
successful for a minority of the following experiments only
(Scheme 1). The present work collects evidence for the
reconciliation of such contradictory observations.
Results and Discussions
1. Syntheses of the Reagents 2. The monochloride 2a had
been observed previously7 as an inseparable byproduct and was
now prepared in two different ways from 1,1,3,3-tetramethyl-
(4) (a) Knorr, R. Chem. ReV. 2004, 104, 3795-3849. (b) Knorr, R. Chem.
ReV. 2004, 104, 3817-3818. (c) Knorr, R. Chem. ReV. 2004, 104, 3831.
(d) Knorr, R. Chem. ReV. 2004, 104, 3832. (e) Knorr, R. Chem. ReV. 2004,
104, 3833. (f) Knorr, R. Chem. ReV. 2004, 104, 3842. (g) Knorr, R. Chem.
ReV. 2004, 104, 3843. (h) Knorr, R. Chem. ReV. 2004, 104, 3841. (i) pp
3823-3825. (j) Knorr, R. Chem. ReV. 2004, 104, 3805. (k) Knorr, R. Chem.
ReV. 2004, 104, 3822. (l) Knorr, R. Chem. ReV. 2004, 104, 3829.
(5) Carbenoids carry both a metal cation and a nucleofugal group at the same
carbon atom: Ko¨brich, G. Angew. Chem. 1972, 84, 557-570, first footnote
therein; Angew. Chem., Int. Ed. Engl. 1972, 11, 473-485.
† Sterically Congested Molecules, 18; for Part 17, see: Bo¨hrer, G.; Knorr,
R.; Bo¨hrer, P.; Schubert, B. Liebigs Ann./Recueil 1997, 193-202.
(1) Modena, G. Acc. Chem. Res. 1971, 4, 73-80.
(2) Glukhovtsev, M. N.; Pross, A.; Radom, L. J. Am. Chem. Soc. 1994, 116,
5961-5962.
(6) Nomenclature: Stang, P. J. Acc. Chem. Res. 1982, 15, 348-354.
(7) Compound 18b in ref 9.
(3) Rappoport, Z. Acc. Chem. Res. 1992, 25, 474-479, and cited literature.
9
10.1021/ja0649116 CCC: $33.50 © 2006 American Chemical Society
J. AM. CHEM. SOC. 2006, 128, 14845-14853
14845

A R T I C L E S
Scheme 1
Knorr et al.
Scheme 2
Dichloromethyllithium (LiCHCl2) is a rather unstable car-
benoid. For the preparation of alcohol 15, LiCHCl2 is most
conveniently11 generated by the deprotonation of methylene-
chloride with lithium diisopropylamide (LDA) in THF in the
presence of the sterically congested ketone 14. The exothermic
reaction sequence must be controlled to keep the internal
temperature below -20 °C, because the lithium alcoholate of
15 would cyclize at temperatures above -10 °C to produce an
R-chlorooxirane.12,13 Cyclization during workup was avoided
by low-temperature protonation, which afforded clean 15 in high
yield. The subsequent dehydration of 15 furnished the pure
dichloride14 2c without side-products.
2. Methyllithium (RLi ) MeLi) and Lithium Phenyl-
acetylide: The Mechanism. Small-scale15 exploratory experi-
ments with MeLi (0.6-0.8 M) and reagents 2a-c (ca. 0.3 M)
in diethyl ether (Et2O) were performed in NMR tubes (5 mm)
at +23 °C, revealing by 1H NMR spectroscopy the approximate
first half-reaction times (t1/2) of 3 h for 2a, 4 days for 2b, and
2 h for 2c.16 The conspicuous deceleration of 2b, obviously a
primary kinetic isotope effect17 with respect to 2a, indicates a
rate-limiting loss of A ) deuterium from 2b (Scheme 3), which
implies the intermediacy of the Cl,Li-alkylidenecarbenoid 6 and
excludes all other mechanisms18 that would not allow for such
an A-CR bond scission (Scheme 1) or would accomplish it in
a step that does not cross the activation barrier. Although most
types of such unsaturated4a carbenoids are unstable above -60
°C, they can be intercepted4b-f by RLi in a fast19 vinylic
substitution reaction: In the example of Scheme 3, the alkenyl-
2-indanone8 (14). In analogy to the preparation9 of the known
monobromide 13, a five-step synthesis was conceived via
“nucleophilic chlorination” of the oxirane9 11 with dry tetra-
ethylammonium chloride and trifluoroacetic acid in boiling
chloroform. The ring-opened product 12a was dehydrated9 to
give 2a, but a corresponding iodoalkene could not be obtained
from 12c.10 A shorter synthesis of 2a used tert-butylmagnesium
chloride for the reduction of 2c (Scheme 2), but a quantitative
yield required prolonged refluxing in THF with 4 equiv of this
stable Grignard reagent over a period of time that varied in an
unpredictable manner. In a less suitable alternative, 2a was the
only reduction product after irradiation of 2c in the presence of
tributylstannane, but it could not be separated from accompany-
ing tributyltin products. The deuterated oxirane [R,R-D2]-11 was
obtained from 14 with [D3]-methyllithium in three steps via the
olefin [R,R-D2]-4a as published9 for the unlabeled substance;
the subsequent ring opening to [R,R-D2]-12a and dehydration
to give 2b were performed as above for 2a.
(11) Taguchi, H.; Yamamoto, H.; Nozaki, H. J. Am. Chem. Soc. 1974, 96, 3010-
3011.
(12) Ko¨brich, G.; Grosser, J.; Werner, W. Chem. Ber. 1973, 106, 2610-2619.
(13) Hofmann, P.; Perez-Moya, L. A.; Kain, I. Synthesis 1986, 43-44.
(14) Mloston, G.; Romanski, J.; Swiatek, A.; Heimgartner, H. HelV. Chim. Acta
1999, 82, 946-956. These authors prepared 2c in a different way and
reported its unassigned 13C NMR spectrum incompletely (CR missing).
(15) Most of the yields (up to 85% of 4) were determined in small-scale runs
(0.1-1 mmol) under nonoptimized conditions.
(16) All t1/2 values in this work are meant to convey semiquantitative rate
information only and to point at primary kinetic isotope effects in reactions
of 2b. They cannot be used directly to quantitate kH/kD ratios because t1/2
increases with decreasing initial concentrations [RLi], which varied by
factors up to three here.
(17) In a related example, the authors conjectured that a tunnel effect contributed
to kH/kD ) 15 as measured for the dedeuteration of (E)-Ph-CHdCD-Cl in
Et2O at 0 °C: Schlosser, M.; Ladenberger, V. Chem. Ber. 1967, 100, 3877-
3892.
(8) Knorr, R.; Mehlsta¨ubl, J.; Bo¨hrer, P. Chem. Ber. 1989, 122, 1791-1793
and refs therein.
(18) For example, kH/kD ) 1.22 was measured for the SN1 solvolysis of D3C-
(t-Bu)CdCdCD-Br by: Schiavelli, M. D.; Ellis, D. E. J. Am. Chem. Soc.
1973, 95, 7916-7917.
(9) Knorr, R.; Freudenreich, J.; von Roman, T.; Mehlsta¨ubl, J.; Bo¨hrer, P.
Tetrahedron 1993, 49, 8837-8854.
(19) Release of an alkylidenecarbene6 R2CdC: from a carbenoid R2CdCLiCl
is usually4a much slower than the substitution reaction and hence unlikely.
(10) Details are given in the Supporting Information.
9
14846 J. AM. CHEM. SOC. VOL. 128, NO. 46, 2006

Carbenoid Chain Reactions, I
A R T I C L E S
Scheme 3
Scheme 4
lithium compound 8d will then arise through incorporation of
a second equivalent of MeLi. However, only one equivalent of
MeLi rather than two (by 1H NMR integration at δ ≈ -2) was
consumed by both reagents 2a and 2c, and the attempted
trapping of 8d by carboxylation (solid CO2) afforded no trace
of the expected carboxylic acid 10d (which can be isolated if
8d is generated20 by an Sn/Li interchange reaction). Instead,
the only products obtained were 4d from 2a,21 4d plus 4e (6:4)
from 2b, and 4f from 2c. An independent synthesis of 4d was
carried out by preparation of a crystalline specimen of 8a22 and
its methylation with iodomethane.
dominantly in step 3, so that step 3 is rate-limiting in the chain
cycle and hence slower than the isotope-independent step 2.27
A ranking of the step rates (velocities of the flux of material)
may thus be expressed in a shorthand notation as 2 > 3 . 1
under the reaction conditions.27 Methyllithium, a tetrameric
aggregate, has in fact proved quite often to be the kinetically
least active base,28,29 despite its high thermodynamic basicity.
The kinetically more active base 8d is more inclined to seize a
proton from other sources in the environment; such a “leakage”
reaction (Scheme 4) will interrupt a running chain, of course,
and the aforesaid chain reaction of 2b was indeed terminated
very soon because the decelerated transfer of A ) deuterium
to give 4e entailed the leakage portions 15% (in THF) or 60%
of 4d (in Et2O), demanding a corresponding input of additional
R′Li ) MeLi for restarting the chains. Thus, an efficient
alkylidenecarbenoid chain process requires both step 1 and the
leakage reaction to be significantly slower than steps 2 and 3,
so that the intermediate 8 and the reagent 2 react almost
exclusively with each other.
The transfer of chlorine from dichloride 2c (Scheme 3) to
8d seemed to be usually fast enough to sustain a carbenoid chain
reaction, unless a lower concentration of 2c (as during the
dropwise addition and especially at the end) retarded the
formation of 4f in step 3, in which case 4d began to appear as
a side-product through leakage as depicted in Scheme 4. This
established a participation of the carbenoid route; but how can
one be sure of a predominance of the chain mechanism in the
absence of the isotope criterion? A convincing demonstration
can be built upon realizing that the organolithium reagents play
the role of bases R′Li (with 2a) or of chlorine acceptors R′Li
(with 2c) in step 1, whereas they are employed as nucleophiles
RLi in step 2. In the presence of a different RLi reagent, less
basic but significantly more nucleophilic, the carbenoid 6 would
be consumed preferentially by RLi in step 2, and the role of
In tetrahydrofuran (THF) solution, MeLi (3 equiv) reacted
much more readily at +23 °C, with the roughly estimated first
t
1/2 values < 2 min for 2a, 15 min for 2b, and < 1 min for 2c.
This evidence16 for a primary kinetic H/D isotope effect23 (2a
versus 2b) points to the alkylidenecarbenoid mechanism 2a f
6 f 8d of Scheme 3; but again only one equivalent of MeLi
1
was consumed by both 2a and 2c according to the H NMR
integrations, and none of the attempted final carboxylations
delivered the acid 10d to be expected from 8d. Only 4d was
obtained from 2a, and only 4f from 2c, while 2b furnished a
pure 15:85 mixture of 4d and 4e, showing that atoms of types
A (albeit lost during the formation of carbenoid 6) were
transferred chiefly (4e) or totally (4d, 4f) to 8d. Reagents 2a-c
are obvious sources of A for a transfer to 8d, as formulated in
more general terms in Scheme 4.
This kind of trapping of an alkenyllithium intermediate such
as 8 by the starting material has been noted occasionally24-26
in the field of alkylidenecarbenoids and explains why the
carboxylations did not provide an acid 10. Such a transfer of A
can also explain the 1:1 stoichiometry, because carbenoid 6 is
regenerated in step 3 of Scheme 4 and will be recycled by the
fast attack of RLi () MeLi here) in step 2 to give 8, which
then awaits the A transfer in step 3, and so forth, creating a
carbenoid chain reaction with 8 (and 6) as the chain carrier(s).
This implies that the reagents 2a-c react faster with the
emanating alkenyllithium compound 8 in step 3 than with R′Li
() MeLi here) in step 1, so that only a small fraction of another
equivalent of MeLi will be “wasted” in step 1. It follows that
the primary kinetic isotope effects of 2a/2b must arise pre-
(20) Knorr, R. and co-workers, unpublished.
(21) The presence of ethoxyethane (4 equiv) did not impair the substitution
reaction with 2a and furnished no product of a cycloaddition reaction to 6,
although the generation of Me2CdCLiBr with MeLi in Et2O in the presence
of enol ethers had afforded (2-propylidene)cyclopropanes55 in high yields.
(22) Knorr, R.; Freudenreich, J.; Polborn, K.; No¨th, H.; Linti, G. Tetrahedron
1994, 50, 5845-5860.
(27) With the assumption that the substitution step 2 with LiCl elimination is
practically irreversible. To be successful, step 2 must occur more rapidly
than the decomposition of the alkylidenecarbenoid which is usually4a fast
at room temperature.
(23) A rough estimate, kH/kD ≈ 11 (( 4), for the primary kinetic isotope effect
in THF was determined10 through competition of 2a with 2b for a
substoichiometric amount of MeLi.
(24) Curtin, D. Y.; Richardson, W. H. J. Am. Chem. Soc. 1959, 81, 4719-
(28) Schlosser, M. Struktur und ReaktiVita¨t polarer Organometalle; Springer-
4728, on p 4721.
Verlag: NewYork, 1973; p 126.
(25) Gu¨nther, H.; Bothner-By, A. A. Chem. Ber. 1963, 96, 3112-3119, on p
3115.
(29) Wardell, J. L. In ComprehensiVe Organometallic Chemistry; Wilkinson,
G., Stone, F. A. G., Abel, E. W., Eds.; Pergamon: Oxford 1982; Vol. 1,
p 50.
(26) Cunico, R. F.; Han, Y.-K. J. Organomet. Chem. 1978, 162, 1-16, on p 3.
9
J. AM. CHEM. SOC. VOL. 128, NO. 46, 2006 14847

A R T I C L E S
Scheme 5
Knorr et al.
that the choice for PhCtCLi and against MeLi is made by
carbenoid 6 in the fast product-determining steps 2B versus 2A,
while the rate-limiting step 3B with the stabilizing R-alkynyl
substituent in 8g can be slower than step 3A with a destabilizing
R-methyl in 8d. Such a deceleration provides independent
evidence for the carbenoid mechanism with MeLi, because a
noncarbenoid process would not have decreased its rate of
production of 4d so much from MeLi in the presence of PhCt
CLi.34 Conversely, a significantly increased observed rate would
be compatible with a mainly noncarbenoid route from 2a to 4d
if combined with a tiny contribution of the carbenoid chain A,
because a catalytic amount of carbenoid 6 might then divert
the majority of 2a to the faster reaction with PhCtCLi via steps
2B and 3B, leaving less material for the formerly main
(noncarbenoid) route.
The dichloride 2c did not react with PhCtCLi (0.32 M, 1.52
equiv) in THF during 3 days at ambient temperature (nor in
t-BuOMe at +34 °C). An added portion (0.25 equiv) of MeLi
was consumed slowly in the course of 40 min, surprisingly
generating 16 as the main product, observed in situ (1H NMR)
and isolated after carboxylation (≈ 15 h later), together with a
small amount of the “normal” product 4h (expected from
chlorine transfer), much of the starting material 2c, and PhCt
C-CO2H (1.40 equiv) but not more than a trace of the product
4f of MeLi incorporation. This decelerating diversion to chain
B established chain A for 2c and verified that 2c was consumed
in step 1 much more slowly than in step 3B (since 8g did not
accumulate). The conclusion that most of 4h must have been
converted rapidly to 16 was confirmed through a control
experiment which furnished 16 from 4h with MeLi in THF.
(Pure 4h can be prepared with 2,4,6-(t-Bu)3C6H2Li in place of
MeLi, as will be shown in section 4.) Owing to this extra drain
on MeLi, the carbenoid chain had to be sustained by a higher
dose (1.1 equiv) of MeLi for a complete conversion of 2c, with
the drawback of an interference by the competing MeLi chain
(steps 2A and 3A in Scheme 5): Carboxylation after one night
yielded 16 (46%), 4f (23%), and PhCtC-CO2H as the only
products, which indicated that PhCtCLi (1.0 equiv) and 4f had
coexisted in THF over an extended period of time instead of
forming 16 (as proved true in a control experiment). The leakage
reaction should be relatively slow in the special case of 8g,
because 4g could not be detected in these runs with 2c and
because closely related alkenyllithium compounds 17b appear
to be comparatively weak bases in view of their ready formation
through deprotonation35,36 of 17a. Considering the above product
ratio of 16/4f ) 46:23, the ranking of step rates for MeLi
reacting with 2c was 2B > 2A . 3A > 3B . 1 under the
reaction conditions.27 The employment of t-BuCtCLi provided
completely analogous results.10
R′Li would be confined to step 1. In the sequel, we have tested
this concept with 2a, whose carbenoid chain mechanism was
established above, and applied it then to 2c for an elucidation
of its behavior.
Phenylethynyllithium is dimeric30,31 in THF and is a much
weaker base (pKa ≈ 31)32,33 than methyllithium. Accordingly,
a THF solution containing 1.8 equivalents of PhCtCLi did not
react with 2a overnight at ambient temperature; but two small
portions of MeLi (2 × 0.09 equiv, in Et2O) were consumed
rapidly, whereafter the product 4g (Scheme 5) was observed
1
by H NMR to increase steadily over the next 140 min at a
strongly diminished velocity. This established that PhCtCLi
generated 4g by chain propagation (step 3B, alternating with
step 2B) without participation of MeLi, that is, with step 1 shut
down. Due to interruptions by the leakage reaction, the chain
had to be restarted with a third portion of MeLi (0.09 equiv)
and reached completion in 6 h. Carboxylation afforded PhCt
C-CO2H (0.8 equiv, from residual PhCtCLi) as the only acid
(no 10g), while almost pure 4g was isolated without a detectable
amount of 4d (Scheme 5), showing that MeLi (if added in small
doses) could not compete successfully for 6 (step 2A) with the
more concentrated PhCtCLi (step 2B). However, 4d became
a byproduct in the presence of more MeLi (0.30 equiv),
especially so in Et2O solution where the very slow reaction of
PhCtCLi, as initiated and sustained by MeLi (0.7 equiv, 0.11
M initially), occurred with a first t1/2 of roughly 50 h at room
temperature.16
3. n-Butyllithium (RLi ) n-BuLi): Counter-Example, and
also Confirmation. The following investigations were confined
to THF solutions, which are known37-40 to contain mainly
Viewed superficially, it may perhaps come as a surprise that
product formation with PhCtCLi was able to suppress the much
faster chain process with MeLi completely. But this amazing
deceleration is easily rationalized by taking into consideration
(34) Several of the decelerations observed in this system are too large to be
ascribed to hypothetic mixed aggregates of PhCtCLi with RLi causing a
retardation of noncarbenoid substitution processes. Such aggregates are
weakly bound and usually hard to detect as the components of very mobile
equilibria in solution. An elucidation of their role would require extended
series of precise rate measurements which are beyond the scope of this
work.
(30) Ha¨ssig, R.; Seebach, D. HelV. Chim. Acta 1983, 66, 2269-2273.
(31) Bauer, W.; Seebach, D. HelV. Chim. Acta 1984, 67, 1972-1988.
(32) Antipin, I. S.; Gareyev, R. F.; Vedernikov, A. N.; Konovalov, A. I. J. Phys.
Org. Chem. 1994, 7, 181-191; Chem. Abstr. 1994, 121, 255158s.
(33) pKa e 21.2 in water: Kresge, A. J.; Pruszynski, P.; Stang, P. J.; Williamson,
B. L. J. Org. Chem. 1991, 56, 4808-4811.
(35) Zweifel, G.; Rajagopalan, S. J. Am. Chem. Soc. 1985, 107, 700-701.
(36) Brandsma, L.; Hommes, H.; Verkruijsse, V. D.; Kos, A. J.; Neugebauer,
W.; Baumga¨rtner, W.; Schleyer, P. v. R. Recl. TraV. Chim. Pays-Bas 1988,
107, 286-295.
(37) Seebach, D.; Ha¨ssig, R.; Gabriel, J. HelV. Chim. Acta 1983, 66, 308-337.
9
14848 J. AM. CHEM. SOC. VOL. 128, NO. 46, 2006

Carbenoid Chain Reactions, I
A R T I C L E S
Scheme 6
achieved simply by using 2b in excess: In a run with a 27:73
mixture (0.118 M) of reagents 2a and 2b competing for a
substoichiometric amount of n-BuLi at room temperature, the
1
in situ H and 13C NMR spectra revealed the presence of 4i
plus 18 (0.21 equiv, 62:38) together with some 4a (step 3B)
and 0.79 equiv of 2a + 2b (0.093 M). The formation of 18
confirmed step 3A, whereas some portion of 4i may have
resulted from leakage. The main component was residual reagent
2b, whereas its unlabeled congener 2a was hardly detectable.
This large (albeit not quantifiable) kinetic H/D isotope effect
established the rate-limiting generation of alkylidenecarbenoid
6 in steps 1 and 3A,B. The efficient formation of substitution
products despite the deficiency of n-BuLi proved that step 2
occurred significantly faster than step 1, in contrast to the
reversed rate relation reported42 for Ph(Me)CdCHCl with
n-BuLi.
The dichloride 2c disappeared from its green THF solution
containing n-BuLi (3.1 equiv, added at -78 °C) within 10 min
at room temperature, as shown by in situ 1H NMR which
revealed the consumption of 2.4 equivalents of n-BuLi with
formation of 8a22 (dCHLi at δH ≈ 6.6). This suggested that
steps steps 3A,B in Scheme 6 had not been achieved. Indeed,
carboxylation after 40 min furnished the acids 10a and 10i (29:
71) in the same ratio as with 2a and 2b (and as also with 2c in
the solvent t-BuOMe), supporting the validity of Scheme 6 with
carbenoid 6 as the common intermediate formed through either
R-deprotonation of 2a or dedeuteration of 2b or the Cl/Li
interchange reaction of 2c. But it must be remarked that to
expect such equal product ratios one would have to presuppose
that the 8a/8i ratio should be changed by the leakage reactions
to a comparable degree in all of these cases. A similar run with
2c and n-BuLi (2.0 equiv) performed at -78 °C in THF/
cyclohexene (2:3) was carboxylated after 2 h, providing 4a and
4i (≈ 1:3) and the acids 10a and 10i (32:68) but no pentanoic
acid (no n-BuLi left) and no cycloaddition4a product of 6 to the
olefinic cosolvent. The different behavior of tert-butyllithium
will be reported separately.
tetrameric and dimeric n-BuLi aggregates. Within 25 min at
room temperature after the addition (at -78 °C) of n-BuLi (2.1
equiv), the monochloride 2a had vanished from the red THF
1
solution whose H NMR spectrum revealed that almost two
equivalents of n-BuLi (δH ≈ -0.75) had been consumed.
Carboxylation after another 30 min afforded a 3:7 mixture of
10a22 and 10i (Scheme 6) as the only organic acids, establishing
the alkenyllithium compounds 8a22 and 8i as final products
before workup. 8a was formed here through hydride transfer4d
(step 2B) from n-BuLi to 6 with expulsion of LiCl (not through
a Cl/Li interchange reaction), as was proven below with the
deuterio reagent 2b. Together with the 1:2 (2a/n-BuLi) stoi-
chiometry, this evidence for intermediates 8a and 8i tells that
the material had passed through steps 1 and 2 in Scheme 6 but
could not be carried through step 3 because 2a had been
deprotonated (step 1) more rapidly by n-BuLi (which is
considerably more active28,29 than MeLi). Hence, the carbenoid
chain was not achieved for want of 2a. The known nonacidic
byproducts 4a41a and 4i41b (ca. 1:4) can be ascribed to the
leakage reactions of 8a and 8i, respectively, with proton transfer
from the solvent or impurities. They were also main products
of a run with 2a and n-BuLi (10 equiv) at -78 °C, which had
been terminated by the addition of DOCH3 (20 equiv) after 7 h
when reagent 2a was almost totally consumed. The crude
material after workup was a mixture of 4a, 4b, 4i, and 18 in
the molar ratio 23:12:43:22, suggesting that only 34% of both
8a and 8i could be trapped by deuteration because 66% had
already fallen victim to adventitious protonation (leakage).
The preceding conclusions were confirmed by treatment of
reagent 2b (0.105 M) with n-BuLi (2.4 equiv) at room
temperature. As expected from steps 1 and 2A,B in Scheme 6,
the isotopic label (A ) D) was completely absent from all
products found after carboxylation, whereas the Cl/Li inter-
change reaction of 2b with n-BuLi would have produced [R-D]-
8a and its derivatives. The acids 10a and 10i (28:72) were
accompanied by pentanoic acid (from residual n-BuLi), while
the nonacidic fraction contained the leakage product 4i41b but
no reagents 2a and 2b. The missing steps 3A,B could be
4. Aryllithium [RLi ) PhLi, 4-(Me3Si)C6H4Li, 2,6-
Alk2C6H3Li, and 2,4,6-(t-Bu)3C6H2Li]: Not Insurmountably
Impeded in Step 2. As an equilibrium mixture of the monomer
and the dimeric aggregate in THF solution,31,43-45 phenyllithium
exhibited a reactivity pattern28,29 intermediate between those of
MeLi and n-BuLi. Will PhLi opt for or against the chain process
in the presence of dichloride 2c? The elucidation was easy in
Et2O solution at room temperature because the chain carrier
8k, generated with PhLi (1.3 equiv) in step 2A of Scheme 7,
was observed by 1H NMR in situ (p-H as a triplet at δ ≈ 6.35
and o-H as a doublet at δ ≈ 6.58 for R-phenyl of 8k),46
whereupon the product 4k of chlorine transfer in step 3A was
isolated (yield at least 50%).15 The small steady-state concentra-
tion (∼0.04 M, ∼0.15 equiv) of 8k remained approximately
constant during the time period from 40 min, when 2c was
(42) Ko¨brich, G.; Ansari, F. Chem. Ber. 1967, 100, 2011-2020, on p 2014.
(43) Bauer, W.; Winchester, W.; Schleyer, P. v. R. Organometallics 1987, 6,
2371-2379.
(44) (a) Reich, H. J.; Green, D. P.; Phillips, N. H. J. Am. Chem. Soc. 1989,
111, 3444-3445. (b) Reich, H. J.; Green, D. P.; Phillips, N. H. J. Am.
Chem. Soc. 1991, 113, 1414-1416.
(38) McGarrity, J. F.; Ogle, C. A. J. Am. Chem. Soc. 1985, 107, 1805-1810.
(39) Heinzer, J.; Oth, J. F. M.; Seebach, D. HelV. Chim. Acta 1985, 68, 1848-
1862.
(40) Bauer, W.; Clark, T.; Schleyer, P. v. R. J. Am. Chem. Soc. 1987, 109,
970-977.
(41) (a) Compound 6 in ref 9. (b) Compound 43 in ref 9.
(45) Gerold, A.; Jastrzebski, J. T. B. H.; Kronenburg, C. M. P.; Krause, N.; van
Koten, G. Angew. Chem. 1997, 109, 778-780; Angew. Chem., Int. Ed.
Engl. 1997, 36, 755-757.
(46) Knorr, R.; Hoang, T. P.; No¨th, H.; Linti, G. Organometallics 1992, 11,
2669-2673.
9
J. AM. CHEM. SOC. VOL. 128, NO. 46, 2006 14849

A R T I C L E S
Scheme 7
Knorr et al.
Scheme 8
1H NMR at room temperature only during the first 2 min and
was complete in 5 min. A preparative run (1.3 equiv of 21m,
performed at +2 °C) furnished the purified carbenoid chain
product 4m (Scheme 8) in 56% yield and no leakage product
4l. Repetitions of this run at +37 °C (17 h) in tert-butyl methyl
ether (t-BuOMe) rather than in THF afforded at most 30-33%
of purified 4m, accompanied by residual 2c and varying portions
of 4l, because the rate of chlorine transfer in step 3 (Scheme 8)
was strongly reduced (a nonchain condition). In fact, the
hampered chain carrier 8m was observed now in situ [δH 0.22
3
(s, Me3Si), 6.65 (d, J ≈ 8 Hz, o-H)] at +35 °C (first t1/2 ≈ 1
h with 1.1 equiv of 21m)16 and at room temperature (first t1/2
≈ 2 h with 2 equiv of 21m) in the presence of 2c, and its leakage
product 4l was not formed during the first 4 h.
2,6-Dimethylphenyllithium (21n), which is monomeric48 or
dimeric49 in THF, was studied at room temperature in t-BuOMe
because of its lower solubility49 in Et2O. Reagent 2c (0.17 M)
present in a roughly 10-fold amount, till 40 h when the
concentration of 2c had dropped to zero, leaving 8k and half
as much of PhLi. Thus ∼1.2 equiv of PhLi was required for
total conversion, indicating that the diminution of 2c via step
3A of Scheme 7 was sufficiently slow to allow step 1 to
consume a considerable portion of 2c. Indeed, a bona fide
sample46 of 8k (∼0.08 M, prepared from the known47 bromo-
alkene 19) was still observed in Et2O solution at room
temperature 45 min after an addition of 2c (∼0.27 M), and it
vanished within <95 min, providing 4k and 4j47 in a 2:1 ratio
and thus confirming the slowness of step 3A (ascribable to a
weakened kinetic basicity of 8k). It follows that 8k and 2c could
not have coexisted for up to 40 h but that 8k was continuously
replenished through the faster step 2A, so that the step rates
can be ranked27 as 2A . 3A > 1 (disturbed chain reaction).
Analytically pure 4k was prepared from bona fide46 8k and
hexachloroethane.10
In THF solution, the reaction of dichloride 2c with PhLi (0.21
M, 1.4 equiv) was over in <10 min at room temperature, and
residual PhLi (1 equiv consumed) was seen in situ by 1H NMR
in an amount corresponding to the small quantity of benzoic
acid (not contaminated by 10k) formed through carboxylation
1 h later, along with 4k (yield 80%) and 4j (13%). The chain
carrier 8k could not be observed under these conditions; but
competition of PhLi with PhCtCLi (∼1:2) provided evidence
for at least partial reaction via carbenoid 6 in Scheme 7: The
products deriving from the intermediates 8k and 8g were formed
in a roughly 1:3 ratio, so that chain B was established, whereas
the fast consumption of 2c did not allow one to demonstrate
the deceleration as required (section 2) for a more quantitative
assessment of chain A. The slow conversion of 4h to 20 was
verified independently with PhLi in THF.
consumed 1.1 equiv of 21n (initially 0.32 M) with a first t1/2
≈
30 min16 and disappeared in ∼6 h, providing mainly the desired
chain product 4n. Thus this conversion proceeded more rapidly
than had been noted above for PhLi in Et2O and for 21m in
t-BuOMe. Apparently, the chain carrier 8n (taken for granted
in analogy with PhLi) was consumed only through chlorination
by 2c in the chain propagation step 3 of Scheme 8, as indicated
by the observed 1:1 stoichiometry and the absence of a leakage
product (H in place of Cl in 4n). The 52% yield of purified 4n
(attained on a larger scale) was higher than in any of numerous
orientating attempts aiming at a cross-coupling catalyzed by Ni
or Pd complexes to give 4n: Reagent 2c appeared to react more
slowly with 21n in the presence of those transition metal
catalysts or of one equivalent of CuCl, whereas 2,6-dimethyl-
phenylmagnesium bromide in Et2O was practically unreactive
toward 2c.
2,4,6-Tri-tert-butylphenyllithium (21p, “supermesityl-
lithium ) LiMes*”),43 which is monomeric43,50,51 in THF
solution, consumed dichloride 2c (∼0.034 M, [LiMes*] ≈ 0.035
M in THF) with a first t1/2 ≈ 6 min16 at room temperature; a
trace of residual LiMes* was detected through carboxylation
after 48 min. A preparative run with [2c] ) 0.37 M furnished
the chloroalkene 4p (Scheme 8, crude yield 78%) together with
an unidentified side-product and ClMes* (yield 8%), which is
the byproduct10 generated along with carbenoid 6 in step 1, so
that (78+8)/78 ) 1.1 equiv of LiMes* were consumed. The
good yield of 4p indicates that the substitution step 2 was not
(48) Reich, H. J.; Sikorski, W. H.; Gudmundsson, B. O¨ .; Dykstra, R. R. J. Am.
Chem. Soc. 1998, 120, 4035-4036.
(49) Wehman, E.; Jastrzebski, J. T. B. H.; Ernsting, J.-M.; Grove, D. M.; van
Koten, G. J. Organomet. Chem. 1988, 353, 133-143.
(50) Fraenkel, G.; Subramanian, S.; Chow, A. J. Am. Chem. Soc. 1995, 117,
6300-6307.
The consumption of 4-(trimethylsilyl)phenyllithium (21m)
in THF by an excess of the dichloride 2c could be watched by
(51) Crystal structure: Maetzke, T.; Seebach, D. HelV. Chim. Acta 1989, 72,
624-630.
(47) Knorr, R.; Lattke, E.; Ra¨pple, E. Liebigs Ann. Chem. 1980, 1207-1215.
9
14850 J. AM. CHEM. SOC. VOL. 128, NO. 46, 2006

Carbenoid Chain Reactions, I
A R T I C L E S
Scheme 9
insurmountably impeded by repulsive interactions between t-Bu
in 21p and the Me groups in reagent 2c. Despite the 8%
contribution of step 1, the competing chain propagation in step
3 must be reasonably efficient because intermediate 8p was not
accumulated and hence the leakage product 4o52 not detected,
not even in case of a shortage of reagent 2c. The carbenoid
chain mechanism was proven through the deceleration34 test:
The formation of 4p was completely suppressed by the
significantly slower chain process of PhCtCLi (0.45 M, 1.5
equiv), which had to be started and later restarted with 0.3
equivalent of LiMes* in two batches. Carboxylation after 6 days
furnished the chloroalkyne 4h (53%, Scheme 5), ClMes* (32%),
residual 2c (28%), and PhCtCCO2H.
The deprotonation of reagent 2a (0.10 mmol, 0.19 M in THF)
with an excess of LiMes* took place with a first t1/2 ≈ 20 min,16
furnishing 4o52 (merely 0.021 mmol), HMes*, and unknown
side-products.10 The intermediacy of carbenoid 6 was established
under the same conditions with reagent 2b which reacted much
more slowly than 2a (at least 10-fold)16 to afford plenty of
ethylene (from THF with LiMes*) and, through a carboxylative
workup 28 h later, HO2C-Mes* (0.13 mmol) and the totally
unlabeled leakage product 4o (again merely 0.021 mmol) but
no rearranged10 material. Such a loss of deuterium revealed that
chain propagation (step 3) was no longer achieved here because
the leakage reaction of intermediate 8p was faster than deuterium
transfer from 2b to 8p.
have been encountered previously where step 3 involved proton
transfer53 from 22c4l,54 or bromine transfer from 24a55 and
24b.4k,56 The carbenoid substitution mechanism of the bromo-
alkenes 25 will be elucidated with subsequently57 reported
evidence.
Experimental Section10
2-(Chloromethylidene)-1,1,3,3-tetramethylindan (2a). (a) From
2c: The dichloride 2c (2.50 g, 9.80 mmol) in anhydrous THF (20 mL)
was added to a THF solution of tert-butylmagnesium chloride (1.36
M, 29.0 mL, 39.4 mmol) under argon cover gas and was heated to
reflux for 120 h. The cooled mixture was cautiously hydrolyzed with
10 mL of 2 M HCl and diluted with another 200 mL, then extracted
with Et2O (3×). The combined extracts were washed until neutral, dried
over MgSO4, and concentrated to afford 2.16 g (100%) of oily
monochloride 2a, contaminated with only a trace of 4a. One crystal-
lization from cooled methanol furnished a colorless powder (1.48 g,
68%) with mp 39-42 °C (see below).
Conclusions
(b) From 12a: The alcohol 12a10 (471 mg, 1.97 mmol) was mixed
with dry pyridine (1.4 mL) under argon cover gas and cooled in ice.
Thionyl chloride (0.28 mL, 3.8 mmol) was added dropwise with stirring.
After further stirring at room temperature for 2 h, the mixture was
diluted with 2 M HCl (30 mL) and extracted with Et2O (3×). The
combined extracts were washed with 2 M HCl (2 × 5 mL), washed
until neutral, and dried over Na2SO4. The residue after concentration
(280 mg) was distilled at 140-155 °C (bath temp.)/14 Torr to give
141 mg (32%) of the slightly contaminated product 2a. Crystallization
from cooled methanol provided an analytically pure powder with mp
The 2-(halogenomethylidene)-1,1,3,3-tetramethylindan re-
agents (2a-c) constitute a well-suited model system for
collecting evidence of alkylidenecarbenoid chain reactions,
particularly because their structural features prevent or disfavor
disturbing alternative modes such as â-elimination,4h ring
expansion,4i or substitution reactions via the ARE3 or SN14j
pathways. A helpful property of this model system is that several
of the carbenoid processes occur slowly enough at room
temperature to estimate first half-conversion times (t1/2). Suitable
mechanistic criteria are primary kinetic H/D isotope effects, the
2/RLi stoichiometry (1:1 or 1:2), the deceleration test with
PhCtCLi as a nucleophile, and the observation of intermediates
by NMR in situ. The reaction rates depend strongly on the
solvent (THF . Et2O or t-BuOMe) and on the R-substituents
R in the chain carriers performing the transfer step 3 which
was always rate-limiting in the chain cycles studied here and
hence slower than the substitution step 2. An undisturbed
carbenoid chain process requires (i) that step 2 occurs signifi-
cantly faster than both the initiating step 1 (which is very often4a
not so) and carbenoid decomposition, and (ii) that step 3 be
substantially faster than both step 1 and the leakage reaction.
Initial cooling (to ≈ -78 °C) may be advisable to minimize
leakage and carbenoid decomposition during reactant mixing.
Carbenoid chain processes are not confined to this model
system: they appear to occur also with 2320 (Scheme 9) but
should not be expected for 1-halogeno-1-alkenes carrying
hydrogen or π-acceptor substituents at the 2-position. Products
of the essential proton-transfer step 3 had been observed in
earlier studies of 22a4d,26 and 22b,4c,25 but further conclusions
were not drawn. We conjecture that additional examples might
1
44-45 °C; H NMR (400 MHz, CDCl3) δ 1.387 (s, 2 3-CH3), 1.600
(s, 2 1-CH3), 6.093 (s, R-H), 7.14, 7.18, 7.24, and 7.25 (4 m, C6H4);
13C NMR (100.6 MHz, CDCl3) δ 27.49 (qq, J ) 127.5 Hz, J ) 4.5
Hz, 2 1-CH3), 32.34 (qq, 1J ) 127.5 Hz, 3J ) 4.5 Hz, 2 3-CH3), 47.89
(m, C1), 48.39 (broader m, C3), 112.49 (d, 1J ) 191.5 Hz, CR), 122.33
(dm, 1J ) 157 Hz, C7), 122.43 (dm, 1J ) 157 Hz, C4), 127.26 (ddd, 1J
1
3
3
1
3
) 159 Hz, J ) 7.4 Hz, C5), 127.45 (ddd J ) 159 Hz, J ) 7.4 Hz,
C6), 148.09 (m, C9), 149.70 (m, C8), 160.23 (m, J ≈ 3.7 Hz, C2),
3
assigned by comparison with the corresponding bromo compound;58
IR (KBr) 2962, 2925, 2863, 1634 (w), 1484, 1457, 846, and 759 cm-1
.
Anal. Calcd for C14H17Cl (220.7): C, 76.18; H, 7.76; Cl, 16.06.
Found: C, 76.45; H, 7.81; Cl, 15.90. Residual dCH NMR absorptions
(1H s δ 6.09, 13C δ 112.5) could not be detected for the R-D derivative
2b.
2-(Dichloromethylidene)-1,1,3,3-tetramethylindan (2c). 2-(Dichloro-
methyl)-1,1,3,3-tetramethyl-2-indanol10 (15, 16.84 g, 61.64 mmol) was
(53) With certain saturated carbenoids, a carbenoid chain based on proton
transfer was apparently progressing in THF solution but obviously not in
Et2O, as judged from the stoichiometries (1:1 and 2:1, respectively) reported
by: Molines, H.; Normant, J.-M.; Wakselman, C. Tetrahedron Lett. 1974,
951-954, Tableau I therein.
(54) Ko¨brich, G.; Merkel, D.; Thiem, K.-W. Chem. Ber. 1972, 105, 1683-
1693.
(55) Hartzler, H. D. J. Am. Chem. Soc. 1964, 86, 526-527.
(56) Fitjer, L.; Kliebisch, U.; Wehle, D.; Modaressi, S. Tetrahedron Lett. 1982,
23, 1661-1664.
(57) Knorr, R.; Pires, C.; Freudenreich, J. In preparation.
(58) Knorr, R.; von Roman, T.; Freudenreich, J.; Hoang, T. P.; Mehlsta¨ubl, J.;
Bo¨hrer, P.; Stephenson, D. S.; Huber, H.; Schubert, B. Magn. Reson. Chem.
1993, 31, 557-565.
(52) Watanabe, S.; Kawashima, T.; Tokitoh, N.; Okazaki, R. Bull. Chem. Soc.
Jpn. 1995, 68, 1437-1448.
9
J. AM. CHEM. SOC. VOL. 128, NO. 46, 2006 14851

A R T I C L E S
Knorr et al.
dissolved in distd. pyridine (81.4 mL) and cooled in ice. Thionyl
chloride (11.30 mL, 154.0 mmol) was added dropwise over 40 min
with stirring under argon gas. The mixture was left at room-temperature
overnight and was then poured into 300 mL of 2 M HCl, which was
extracted with Et2O (3 × 300 mL). The combined extracts were shaken
with 2 M HCl (2 × 200 mL), washed until neutral, and dried over
Na2SO4. Concentration and drying in vacuo afforded 15.30 g (97%) of
pure dichloride 2c: pale-yellow plates with mp 119-121 °C from
ethanol (ref 14: 119-121 °C); 1H NMR (400 MHz, CDCl3) δ 1.59 (s,
4 1-/3-CH3), 7.14 (m, 4-/7-H), 7.25 (m, 5-/6-H), as in ref 14; 13C NMR
poured into distd. water (100 mL) and diluted with Et2O. The separated
aqueous layer was extracted with Et2O (3 × 80 mL). The combined
Et2O phases were washed until neutral, dried over MgSO4, and
concentrated to yield 8.81 g of solid material, consisting of mainly 4m
with only a trace of the leakage product 4l but no 2c. Slow
recrystallization from ethanol (∼50 mL) afforded almost pure 4m as
colorless needles in two fractions (4.404 g, 56%): mp 134-135 °C
1
(ethanol); H NMR (400 MHz, CDCl3) δ 0.29 (s, SiMe3), 1.18 (s, 2
3-CH3), 1.76 (s, 2 1-CH3), 7.04 (dm, 4-H), 7.19-7.27 (m, 5-/6-/7-H),
3
3
7.32 (dm, J ) 8 Hz, 2 o-H), and 7.52 (dm, J ) 8 Hz, 2 m-H); 13C
NMR;10 IR (KBr) 2955, 1649 (w), 1588, 1486, 1363, 1250 (s), 1115,
840, 808, and 758 cm-1. Anal. Calcd for C23H29ClSi (369.0): C, 74.86;
H, 7.92; Cl, 9.61. Found: C, 75.19; H, 7.78; Cl, 9.33. - The mother
liquor, concentrated to 5 mL, deposited small needles of 1,4-bis-
(trimethylsilyl)benzene (108 mg, 1.7%) that had been imported with
the starting material: mp 85-86 °C (ref 59: 88 °C; ref 60: 88-89
1
3
(100.6 MHz, CDCl3) δ 27.4 (qq, J ) 127.8 Hz, J ) 4.5 Hz, 4 1-/3-
1
CH3), 50.2 (m, C1,3), 115.8 (sharp s, CR), 122.4 (dm, J ) 158 Hz,
1
3
C4,7), 127.5 (ddd, J ) 159.9 Hz, J ) 7.5 Hz, C5,6), 148.7 (m, C8,9),
155.1 (m, C2), in disagreement with ref 14; IR (KBr) 2990, 2963 (s),
2928, 2867, 1583, 1485, 1454, 1363, 900 (s), 856 (s), and 755 (s) cm-1
(compare ref 14). Anal. Calcd for C14H16Cl2 (255.2): C, 65.89; H, 6.32;
Cl, 27.79. Found: C, 66.02; H, 6.35; Cl, 27.65.
1
°C; ref 61: 94-96 °C); H NMR as in ref 62.
2-(R-Chloro-2,6-dimethylbenzylidene)-1,1,3,3-tetramethylindan
(4n). t-BuLi (4.49 mmol) in pentane (2.64 mL) was added dropwise
with stirring at -78 °C under argon cover gas to 2-bromo-1,3-
dimethylbenzene (0.30 mL, 2.24 mmol) in t-BuOMe (4.0 mL), affording
2,6-dimethylphenyllithium (2.24 mmol): 1H NMR δ 2.50 (s, 2 o-CH3)
and 6.77 (narrow m, 3 H). The solution deposited a copious precipitate
of LiBr and was stirred at room temperature for 30 min, then treated
with reagent 2c (500 mg, 1.96 mmol), warmed at 32-35 °C for 3 h,
and diluted with Et2O and water. The aqueous layer was extracted with
Et2O (3×), and the combined Et2O phases were washed until neutral,
dried over MgSO4, and concentrated to give 655 mg of crude 4n,
contaminated with m-xylene and other side-products but not more than
a trace of reagent 2c. One crystallization from EtOH afforded 334 mg
(52%) of pure 4n: mp 130-131.5 °C; 1H NMR (400 MHz, CDCl3) δ
1.14 (s, 2 1-CH3), 1.79 (s, 2 3-CH3), 2.37 (s, 2 o-CH3), 7.03 (m, 4-H
2-Ethylidene-1,1,3,3-tetramethylindan (4d). MeLi (8.60 mmol) in
Et2O (6.90 mL) was added with stirring under argon cover gas to the
solution of monochloride 2a (633 mg, 2.87 mmol) in Et2O (10.0 mL).
After one night at room temperature, the mixture was poured onto solid
CO2, warmed, and diluted with Et2O and 2 M NaOH. The acidified
NaOH layer furnished no organic acid. The Et2O phase was washed
until neutral, dried with MgSO4, and concentrated to yield 4d (490
mg, 85%) along with a trace of residual reagent 2a. The material was
distilled at 120-170 °C (bath temperature)/12 Torr and then crystallized
1
from cooled methanol to give a colorless powder: mp 34-35 °C; H
NMR (400 MHz, CDCl3) δ 1.31 (s, 2 3-CH3), 1.50 (s, 2 1-CH3), 1.87
3
3
(d, J ) 7.3 Hz, R-CH3), 5.48 (q, J ) 7.3 Hz, R-H), 7.15, 7.18, and
7.21 (1 + 1 + 2 arom. H, C6H4); 13C NMR;10 IR (KBr) 2960, 2862,
1483, 1457, and 755 cm-1. Anal. Calcd for C15H20 (200.3): C, 89.94;
H, 10.06. Found: C, 89.59; H, 9.91.
3
3
or 7-H), 7.06 (d, J ) 7.5 Hz, 2 m-H), 7.17 (pseudo-t, J ) 7.7 Hz,
p-H), 7.22 (m, 3 H of C6H4); 13C NMR;10 IR (KBr) 2992, 2961, 2927,
2865, 1640 (w), 1591 (w), 1485, 1459, 1360, 838, 784, 777, and 760
cm-1. Anal. Calcd for C22H25Cl (324.9): C, 81.33; H, 7.76; Cl, 10.91.
Found: C, 81.03; H, 7.92; Cl, 10.42. In cases of inefficient stirring
but otherwise identical conditions, the crude material contained some
residual reagent 2c and a “carbene dimer”57 as a side-product.
2-(1-Chloroethylidene)-1,1,3,3-tetramethylindan (4f). Dichloride
2c (1.53 g, 6.00 mmol) in anhydrous THF (10.0 mL) was added
dropwise within 3 min at room temperature under argon cover gas to
a stirred solution of MeLi (6.60 mmol) in Et2O (6.00 mL) and THF
(14.8 mL). The exothermic reaction was terminated after another 10
min by carboxylation on solid CO2. The warmed-up material was
dissolved in Et2O and 2 M NaOH. The separated and acidified NaOH
layer afforded no organic acid. The Et2O phase was washed until neutral,
dried with MgSO4, and concentrated to furnish a mixture (1.29 g) of
4f (yield 82%) and 4d (9%). Pure 4f crystallized as a beige powder
2-(2,4,6-Tri-tert-butylbenzylidene)-1,1,3,3-tetramethylindan (4o)10;
2-(R-Chloro-2,4,6-tri-tert-butylbenzylidene)-1,1,3,3-tetramethyl-
indan (4p)10; 2-(1,1,3,3-Tetramethyl-2-indanylidene)propanoic Acid
(10d). To be published in ref 57; 2-(1,1,3,3-Tetramethyl-2-indan-
ylidene)hexanoic Acid (10i)10; 2-Chloromethyl-1,1,3,3-tetramethyl-
2-indanol (12a)10; 2-(Dichloromethyl)-1,1,3,3-tetramethyl-2-indanol
1
from methanol (2×): mp 108-109 °C; H NMR (400 MHz, CDCl3)
δ 1.51 (s, 2 3-CH3), 1.61 (s, 2 1-CH3), 2.35 (s, R-CH3), 7.12 (m, 4-H),
7.14 (m, 7-H), 7.23 (m, 5-H), and 7.24 (m, 6-H), assigned by the
NOESY correlations R-CH3 T 3-CH3 T 4-H T 5-H and 1-CH3 T
7-H T 6-H; 13C NMR;10 IR (KBr) 2959, 2928, 1644 (w), 1487, 1455,
and 761 cm-1. Anal. Calcd for C15H19Cl (234.8): C, 76.74; H, 8.16;
Cl, 15.10. Found: C, 77.17; H, 8.11; Cl, 14.27.
(15)10;
2-(1-Methyl-3-phenyl-2-propyn-1-ylidene)-1,1,3,3-tetra-
methylindan (16)10; 2-(1,3-Diphenyl-2-propyn-1-ylidene)-1,1,3,3-
tetramethylindan (20).10
Preparation of Bromo-2,4,6-tri-tert-butylbenzene (BrMes*). We
prepared BrMes* from HMes* by a modification of a published63
procedure, because it cannot be made in a reasonable yield from
H2NMes* by diazotization64 (compare also ClMes*)10 and because the
commercially available material is very expensive. We found it
expedient to double the recommended63,65 amount (1.2 equiv) of
bromine and to raise the reaction temperature to 100 °C in the following
protocol.
2-(3-Phenyl-2-propyn-1-ylidene)-1,1,3,3-tetramethylindan (4 g)10;
2-(1-Chloro-3-phenyl-2-propyn-1-ylidene)-1,1,3,3-tetramethyl-
indan (4h)10; 2-Pentylidene-1,1,3,3-tetramethylindan (4i). Spectra in
ref 41b; 2-(R-Chlorobenzylidene)-1,1,3,3-tetramethylindan (4k)10;
2-(4-Trimethylsilylbenzylidene)-1,1,3,3-tetramethylindan (4l).10
2-(R-Chloro-4-trimethylsilylbenzylidene)-1,1,3,3-tetramethyl-
indan (4m). An oven-dried Schlenk flask (250 mL) was charged with
1-bromo-4-(trimethylsilyl)benzene10 (6.430 g, 28.06 mmol) in anhydrous
THF (60 mL) and cooled to -78 °C under argon cover gas. t-BuLi
(56.1 mmol) in pentane (33.00 mL) was added dropwise with stirring,
forming 4-trimethylsilylphenyllithium (21m): 1H NMR δ +0.16 (s,
(59) Clark, H. A.; Gordon, A. F.; Young, C. W.; Hunter, M. J. J. Am. Chem.
Soc. 1951, 73, 3798-3803.
(60) Allred, A. L.; Bush, L. W. J. Am. Chem. Soc. 1968, 90, 3352-3360.
(61) Noltes, J. G.; van der Kerk, G. J. M. Recl. TraV. Chim. Pays-Bas 1962,
81, 565-577, on p 569.
3
3
(62) Haubold, W.; Herdtle, J.; Gollinger, W.; Einholz, W. J. Organomet. Chem.
1986, 315, 1-8.
SiMe3), 7.10 (d, J ≈ 7 Hz, 2 m-H), 7.92 (d, J ≈ 7 Hz, 2 o-H); in
t-BuOMe +0.16, 7.24, and 8.08 with 3J ) 7 Hz. The deep-red solution
was stirred without cooling for 10 min and then stirred in an ice bath
during the slow addition of dichloride 2c (5.400 g, 21.16 mmol) in
small portions. After further stirring for 30 min, the cold solution was
(63) Cowley, A. H.; Norman, N. C.; Pakulski, M. Inorg. Synth. 1990, 27, 235-
237.
(64) Betts, E. E.; Barclay, L. R. C. Can. J. Chem. 1955, 33, 1768-1774.
(65) Pearson, D. E.; Frazer, M. G.; Frazer, V. S.; Washburn, L. C. Synthesis
1976, 621-623.
9
14852 J. AM. CHEM. SOC. VOL. 128, NO. 46, 2006

Carbenoid Chain Reactions, I
A R T I C L E S
2,4,6-Tri-tert-butylbenzene (HMes*, 24.44 g, 99.2 mmol) was
dissolved in freshly distilled trimethyl phosphate65 (300 mL) with
stirring and warming up to 54 °C. The stirred solution turned red upon
the dropwise addition of elemental bromine (11.68 mL, 228 mmol).
After heating at a reflux condenser at 100 °C for 22 h, the cooled
solution deposited pale yellow crystals which were isolated by suction,
washed thoroughly with distd. water, and dried in a desiccator with
KOH under vaccum. This crude product (31.43 g, 97%) was almost
uncontaminated and could be used as such in most cases. It was
recrystallized from ethanol (550 mL) to yield glistening platelets (19.81
g, 61%) with mp 167-169 °C (refs 63, 64: 172-174 °C63 after two,
177-178 °C64 after four recrystallizations). 1H NMR (400 MHz, CDCl3)
δ 1.31 (s, 4-t-Bu), 1.58 (s, 2-/6-t-Bu), 7.41 (s, 3-/5-H), compare ref
63; 13C NMR (100.6 MHz, CDCl3) δ 31.0 (2-/6-CMe3), 31.4 (4-CMe3),
35.0 (4-CMe3), 38.4 (2-/6-CMe3), 121.6 (C1), 123.7 (C3,5), 148.4 (C4),
148.6 (C2,6).
Acknowledgment. We gratefully acknowledge the receipt of
generous subsidies from the Deutsche Forschungsgemeinschaft.
R.K. thanks Professor Herbert Mayr for his most helpful support.
Supporting Information Available: Preparatory synthetic
studies; further substitution products; 1H and 13C NMR assign-
ments; side-products; estimation of a kinetic H/D isotope effect.
This material is available free of charge via the Internet at
http://pubs.acs.org.
JA0649116
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