β-Silyl organocuprates: The grail of organocuprate chemistry?

Full text of DOI:10.1021/ja962559y

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10906
J. Am. Chem. Soc. 1996, 118, 10906-10907
Table 1. Logarithmic Reactivity Profiles of Selected
Organocopper Reagents: Yields (%) of 2a
â-Silyl Organocuprates: The Grail of
Organocuprate Chemistry?1a
time (h)b
Steven H. Bertz,*,1b Magnus Eriksson,1c Guobin Miao,1d and
James P. Snyder1e
reagent
1
0.1
0.01
0.001
BuCu(TMSM)Li‚LiI
ether
THF
100
99
99
99
99
95
98
82
Complexity Study Center
Mendham, New Jersey 07945
Department of Organic Chemistry
Chalmers UniVersity of Technology
S-412 96 Go¨teborg, Sweden
Department of Chemistry
BuCu(TMSM)Li‚LiCN
ether
THF
99
99
99
98
99
96
99
84
BuCu(HMDS)Li‚LiI
ether
THF
99
55
99
13
99
10
84
3
Brigham Young UniVersity
BuCu(TMST)Li‚LiI
ProVo, Utah 84602
ether
THF
94
72
89
20
85
7
61
2
Chemistry Department, Emory UniVersity
Atlanta, Georgia 30322
BuCu(Th)Li‚LiCN
ether
THF
99
89
99
74
89
57
64
32
ReceiVed July 25, 1996
Bu2CuLi‚LiCN
Organocuprates R2CuLi‚LiX,2 prepared from 2 equiv of
lithium reagent and a copper(I) salt CuX (typically X ) I, Br,
CN), are indispensible reagents for selective carbon-carbon
bond formation.3 With few exceptions, only one of the two R
groups in these “Gilman reagents” is utilized in synthetic
applications.4 A mixed cuprate RR′CuLi‚LiX which is highly
reactive yet selectively transfers only one group R has been
the “holy grail” of organocuprate chemistry.
ether
THF
97
84
97
82
95
67
94
54
a Compound 2 ) 3-butylcyclohexanone: measured by using GLC
and the internal standard method. All reactions were run at -78 °C
on a 1.00 mmol scale (0.10 M). b Time: 1 h ) 60 min, 0.1 h ) 6 min,
0.01 h ) 36 s, 0.001 h ) 4 s.
into the auxiliary group R′, we would create a cuprate of
unparalleled reactivity.
The two basic approaches to this problem have been the use
of a nontransferred group R′ (i) bonded to Cu at an sp or sp2
carbon (e.g., alkynyl5 or 2-thienyl,6,7 respectively) or (ii) attached
to Cu via a heteroatom such as S,8 N,9,10 or P.9-12 None of
these has been ideal. Cyanocuprates RCu(CN)Li are convenient
to prepare but are relatively unreactive.13 Phosphidocuprates
are thermally stable9 and highly reactive,10-12 but the precursor
phosphines are expensive and toxic. The best solution to date
appears to be RCu(Th)Li‚LiI (Th ) 2-thienyl), introduced by
the Nilsson group.6 The cyano analogs RCu(Th)Li‚LiCN7
appear to have fundamentally similar reactivities.14
In this paper we report a new approach to this problem
derived from our work on the mechanism of TMSCl acceleration
of organocuprate conjugate addition. We proposed a new
mechanism in which coordination of TMSCl to Cu allows the
transition state to be stabilized by a silicon atom in the
â-position.15a Thus, we reasoned that by building a â-silicon
We have reduced this concept to practice in three ways. First,
addition of RLi (1 equiv) to ((trimethylsilyl)methyl)copper(I),
prepared by the procedure of Lappert et al.,16 yields mixed
cuprates RCu(CH2SiMe3)Li. We have prepared these new
((trimethylsilyl)methyl)cuprates from CuI as well as CuCN, and
we find that they are extraordinarily reactive in both ether and
THF (Vide infra). They have the additional advantage of a most
innocuous byproduct upon aqueous workup, viz. tetramethyl-
silane. We propose to name them TMSM-cuprates.
A second class of â-silylcuprates combines our new concept
with our previous N-heterocuprates.9,10 Thus, hexamethyl-
disilazidocuprates RCu[N(SiMe3)2]Li are conveniently prepared
from RLi and copper(I) bis(trimethylsilyl)amide.17 In diethyl
ether these new reagents are also extremely reactive, and their
byproducts upon aqueous workup, NH3 and TMSOTMS, are
relatively benign. (Organocopper reactions are often quenched
with aqueous ammonium salt.) We call them HMDS-cuprates.
The third class of â-silylcuprates combines our new concept
with Posner’s thiocuprates.8 ((Trimethylsilyl)thio)cuprates RCu-
(SSiMe3)Li are prepared from RLi and CuSSiMe3, which is
formed in situ from CuI and LiSSiMe3.18 These ((trimethyl-
silyl)thio)cuprates (TMST-cuprates) also have excellent reactiv-
ity in ether. In addition to TMSOTMS, aqueous workup gives
H2S, which improves the yields of some organocuprate reac-
tions.4
(1) (a) New Copper Chemistry, part 27. For part 26, see ref 14; for part
25, see ref 15a; for part 24, see ref 19. (b) Complexity Study Center. (c)
Chalmers University of Technology. (d) Brigham Young University. (e)
Emory University.
(2) For recent compendious reviews, see: Bertz, S. H.; Fairchild, E. H.
In Encyclopedia of Reagents for Organic Synthesis; Paquette, L., Ed.;
Wiley: New York, 1995; Vol. 2, p 1312 (CuBr), 1324 (CuCl), 1341
(CuCN), 1346 (CuI).
(3) (a) For extensive tables of examples, see: Lipshutz, B. H.; Sengupta,
S. Org. React. 1992, 41, 135. (b) See p 221 of ref 3a.
(4) Bertz, S. H.; Dabbagh, G.; Williams, L. M. J. Org. Chem. 1985, 50,
4414.
(5) Corey, E. J.; Beames, D. J. J. Am. Chem. Soc. 1972, 94, 7210.
(6) Malmberg, H.; Nilsson, M.; Ullenius, C. Tetrahedron Lett. 1982, 23,
3823.
(7) Lipshutz, B. H.; Kozlowski, J. A.; Parker, D. A.; Nguyen, S. L.;
McCarthy, K. E. J. Organomet. Chem. 1985, 285, 437.
(8) Posner, G. H.; Whitten, C. E.; Sterling, J. J. J. Am. Chem. Soc. 1973,
95, 7788.
(9) Bertz, S. H.; Dabbagh, G. J. Chem. Soc., Chem. Commun. 1982, 1030.
(10) Bertz, S. H.; Dabbagh, G.; Villacorta, G. M. J. Am. Chem. Soc.
1982, 104, 5824.
(11) Bertz, S. H.; Dabbagh, G. J. Org. Chem. 1984, 49, 1119.
(12) Martin, S. F.; Fishpaugh, J. R.; Power, J. M.; Giolando, D. M.;
Jones, R. A.; Nunn, C. M.; Cowley, A. H. J. Am. Chem. Soc. 1988, 110,
7226.
Logarithmic reactivity profiles14,15a (LRPs) for BuCu(TMS-
M)Li, BuCu(HMDS)Li, and BuCu(TMST)Li are compared to
those for BuCu(Th)Li‚LiCN and Bu2CuLi‚LiCN in Table 1. A
LRP is generated by quenching an archtypal reaction after a
series of times which span as many orders of magnitude as
possible. The butyl((trimethylsilyl)methyl)cuprate is signifi-
cantly more reactive toward 2-cyclohexenone (1) than the
(15) (a) Bertz, S. H.; Miao, G.; Rossiter, B. E.; Snyder, J. P. J. Am.
Chem. Soc. 1995, 117, 11023. (b) Snyder, J. P. J. Am. Chem. Soc. 1995,
117, 11025.
(16) Jarvis, J. A. J.; Pearce, R.; Lappert, M. F. J. Chem. Soc., Dalton
Trans. 1977, 999.
(17) Walton, D. R. M. In Encyclopedia of Reagents for Organic
Synthesis; Paquette, L., Ed.; Wiley: New York, 1995; Vol. 2, p 1312.
(18) (a) Steliou, K.; Salama, P.; Corriveau, J. J. Org. Chem. 1985, 50,
4969. (b) Segi, M.; Kato, M.; Nakajima, T.; Suga, S.; Sonoda, N. Chem.
Lett. 1989, 1009.
(13) Gorlier, J.-P.; Hamon, L.; Levisalles, J.; Wagnon, J. J. Chem. Soc.,
Chem. Commun. 1973, 88.
(14) Bertz, S. H.; Miao, G.; Eriksson, M. Chem. Commun. 1996,
815.
S0002-7863(96)02559-0 CCC: $12.00 © 1996 American Chemical Society

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Communications to the Editor
J. Am. Chem. Soc., Vol. 118, No. 44, 1996 10907
Table 2. Thermal Stability of BuCu(TMSM)Li‚LiI and
BuCu(Th)Li‚LiI: Yields (%) of 4 (and 5 or 6)a
etophenone (5) were also formed with the excess (2.2 equiv)
of 3. With 1 equiv of 3, the yields of 4 were 100% in ether
and 96% in THF (along with 3% of 5). Authentic samples of
the side products were prepared via the reactions of (TMSM)2-
CuLi‚LiI with 1 and 3, respectively.
For comparison, the corresponding data for the thienyl mixed
cuprates are also summarized in Table 2. The contrast between
the ((trimethylsilyl)methyl)cuprates and the thienylcuprates is
especially stark at 25 °C, where the former retain almost all of
their reactivity but the latter are defunct. Also, more of the
side product (in this case 2-benzoylthiophene (6)) from the
transfer of the “nontransferred” ligand is formed, especially in
THF.
The thermal stabilities of the intermediates also deserve
comment. While (TMS)CH2Cu and (TMS)2NCu are stable at
0 °C, (TMS)SCu is not and deposits Cu metal at this temper-
ature. It is prepared at -20 °C; see the Supporting Information.
The composition of the reagent responsible for conjugate
addition was probed by performing density functional theory
(DFT)19 geometry optimizations (B3LYP/LANL2DZ basis set)19
for the TMSM and Me homocuprates and the mixed cuprate
species, as summarized in eq 1. The calculated energy for this
isodesmic reaction is 1.8 kcal/mol. This corresponds to
Boltzmann distributions containing 99.1% mixed cuprate at -78
°C, 96.5% at 0 °C, and 95.4% at 25 °C. The results indicate
that the mixed cuprate is strongly favored over the corresponding
homocuprates at the temperatures used in our studies.
temp (°C)
reagent
-78
0
25
BuCu(TMSM)Li‚LiI
ether
THF
98 (1)b
95 (3)
98 (2)
95 (3)
94 (4)
92 (3)
BuCu(Th)Li‚LiI
ether
74 (10)c
85 (11)
58 (12)
61 (21)
13 (17)
3 (42)
THF
a Compound 4 ) butyl phenyl ketone, 5 ) (trimethylsilyl)acetophe-
none, 6 ) 2-benzoylthiophene: measured by using GLC and the internal
standard method. All reactions were run on a 1.00 mmol scale (0.10
M). b Yields of 5 in parentheses. c Yields of 6 in parentheses.
corresponding 2-thienylcuprate in both ether and THF. The
((trimethylsilyl)methyl)cuprate is also more reactive than the
cyano Gilman reagent: slightly more reactive in ether, consider-
ably more in THF. In fact, the yields of 3-butylcyclohexanone
(2) are quantitative or nearly so (99-100%) from BuCu-
(TMSM)Li‚LiI and BuCu(TMSM)Li‚LiCN in both ether and
THF. Even at the shortest time we can reliably obtain (4 s),
the yields in ether are virtually quantitative (98-99%). No
3-((trimethylsilyl)methyl)cyclohexanone was detected.
Within experimental error, the ((trimethylsilyl)methyl)cu-
prates prepared from CuI and CuCN have equal reactivities.
The reactivities of the thienylcuprates prepared from CuI and
CuCN are almost equal, which is attributable to stabilization
of the transition state by the thienyl group.14 We believe that
the â-trimethylsilyl group exerts an even greater effect, since
the yields from the ((trimethylsilyl)methyl)cuprates are higher
and their dependence on the precursor salt is lower (negligible).
The BuCu(HMDS)Li‚LiI reagent also has excellent reactivity
in ether but not in THF. The yield from the BuCu(TMST)Li‚
LiI reagent is slightly lower than from the HMDS-cuprate in
ether but significantly better in THF after 1 h (-78 °C). We
note that all yields fall off faster in THF than in ether. In
general, yields from conjugate addition reactions of cuprates
are not as good in THF as in ether.2,3 The difference between
ether and THF is much less for the ((trimethylsilyl)methyl)-
cuprates than for any of the other reagents.
The butyl group was chosen for study because it has sufficient
reactivity at -78 °C, where thermal decomposition is not a
complicating factor. Nevertheless, it also has two â-hydrogen
atoms, which make it susceptible to thermal decomposition at
higher temperatures. Therefore, we studied the thermal de-
composition of the ((trimethylsilyl)methyl)cuprates by using the
paradigm introduced previously.9
The cuprates were aged at various temperatures (-78, 0, or
25 °C) for 0.5 h and then quenched with benzoyl chloride (3)
at -78 °C. The amount of butyl phenyl ketone (4) present is
then a measure of the (minimum) amount of viable reagent that
remains. Table 2 summarizes the thermal stability data, which
show that this new reagent is more stable than previous
homocuprates or heterocuprates.9 For example, in ether the
corresponding yields for Bu2CuLi‚LiI are 96, 89, and 82%, and
for Bu2CuLi‚LiCN they are 99, 95, and 84%, respectively.9
The yields of 4 were slightly lower than the yields of 2 (Vide
supra), since small amounts (1-4%) of (trimethylsilyl)ac-
2[(TMSM)CuMe]- F [(TMSM) Cu]- + [Me Cu]- (1)
R
2
2
In conclusion, we have found that by building a â-silicon
atom into an organocuprate, the resulting reagent is (i) highly
reactive, (ii) thermally stable, and (iii) economical as far as the
transferred group is concerned. We have demonstrated this for
the two most important applications of organocopper reagents,
conjugate addition and ketone formation,20 although more work
is needed to fully define the scope and limitations of these new
reagents. As far as cyano Gilman reagents are concerned, it
has been noted that “those prepared from 2 equivalents of the
same organolithium and 1 equivalent of copper(I) cyanide are
more reactive species relative to those containing a second
residual ligand...”3b It would appear that we have invented the
first mixed cuprate that is more reactive than the corresponding
homocuprates. Finally, we believe that this work illustrates the
extension of the Eaborn â-silyl effect21 to metal centers.
Acknowledgment. We thank Professor O. Wennerstro¨m for making
it possible for S.H.B. and M.E. to work in his laboratories. J.P.S. wishes
to express his gratitude to Professors K. Morokuma, D. Liotta, and A.
Padwa for their support and collegiality during his sabbatical at the
Emerson Center for Scientific Computing (Emory University).
Supporting Information Available: Experimental details (1 page).
See any current masthead page for ordering and Internet access
instructions.
JA962559Y
(19) Snyder, J. P.; Bertz, S. H. J. Org. Chem. 1995, 60, 4312.
(20) Posner, G. H.; Whitten, C. E.; McFarland, P. E. J. Am. Chem. Soc.
1972, 94, 5106.
(21) (a) Eaborn, C. J. Organomet. Chem. 1975, 100, 43. (b) Eaborn, C.
J. Chem. Soc., Chem. Commun. 1972, 1255 and references cited therein.