Selective copper-catalyzed coupling reactions of (α-acetoxyhexyl)tricyclohexyltin

Full text of DOI:10.1021/jo961161h

6492
J . Org. Chem. 1996, 61, 6492-6493
of this class of derivatives. The intermediacy of a copper
species in mixed Pd/Cu-catalyzed Stille couplings, as well
as direct Sn-Cu transmetalations, have also been re-
cently reported in other studies.6
Selective Cop p er -Ca ta lyzed Cou p lin g
Rea ction s of
(r-Acetoxyh exyl)tr icycloh exyltin
We were intrigued by these results5 given the low
degree of butyl group transfer reported and the lack of a
dimeric species.7 We had earlier studied the reactions
of R-alkoxyorganocopper and -cuprate reagents (obtained
via initial Sn-Li transmetalation) with several electro-
philes.8 In these cases, formation of a dimeric species
was frequently noted as a byproduct. We then examined
the reaction of R-acetoxyhexyl(tributyltin) 1a with ben-
zoyl chloride in the presence of a Pd/Cu catalyst (eq 2).9
The reaction led to the formation of three products, the
R-acetoxyhexyl (R-OAcHex) coupling product 2, the dimer
3, and the Bu transfer product 4 (eq 2). The 57% isolated
yield of 2 was similar to that reported,5a but the dimer 3
was also isolated in 39% yield as well as 42% of the Bu
transfer product. Note that 96% of the R-OAcHex ligand
of stannane 1a is accounted for in this reaction. The
molar ratio of the isolated products 2:3:4 was 48:16:36.10
Russell J . Linderman* and J ames M. Siedlecki
Department of Chemistry, North Carolina State University,
Raleigh, North Carolina 27695-8204
Received J une 20, 1996
The selective coupling reactions of R-alkoxyalkyl groups
from nonsymmetric tetraalkylstannanes has been a
subject of study for some time (eq 1). Stille and co-
workers examined Pd-catalyzed coupling reactions of
MOMOCH2SnBu3 and MOMOCH2SnMe3 with benzoyl
chloride.1 Methoxymethyl group transfer occurred pref-
erentially to Bu or Me group transfer; however, the
selectivity was poor (2.5:1 or 3:1, respectively). J ulia and
co-workers reported coupling of MPMOCH2SnBu3 with
a vinyl iodide in modest yields, but also noted significant
butyl transfer.2 Vedejs and co-workers reported a solu-
tion to the selective alkyl transfer problem via intramo-
lecular activation of tin in a 1-aza-5-stannabicyclo[3.3.3]-
undecane system.3 In this example, selective transfer of
primary alkyl groups including the CH2OMOM group
was realized in Stille coupling reactions. We employed
an intramolecular variant of the Stille coupling reaction
of an (R-alkoxyalkyl)stannane to provide a furanone;
however, we subsequently found that the reaction was
capricious, often resulting in no coupling product.4 More
recently, Falck and co-workers have shown that Pd/Cu
cocatalyst systems are effective for the selective transfer
of (R-acetoxy- or (R-(benzoyloxy)benzyl)tributylstannanes
in coupling reactions with aryl or aliphatic acid chlor-
ides.5ab (R-Acetoxyalkyl)tributylstannanes were not as
effective in coupling reactions with aryl acid chlorides
and were ineffective in attempted coupling reactions with
aliphatic acid chlorides. (R-Methoxymethoxy- or (R-meth-
oxyalkyl)tributylstannanes did not provide coupling prod-
ucts. Subsequently, Falck and co-workers achieved a
significant advance by discovering that thiocarbamate or
thionoacetoxy derivatives reacted with allyl bromides and
aliphatic acid chlorides in the presence of a copper(I)
catalyst alone.5c Intramolecular stabilization of a pre-
sumed copper intermediate by the sulfur atom was
speculated as a probable rationale for the unique success
Interestingly, dimer 3 formation increased and the
amount of the R-OAcHex product 2 significantly de-
creased when the reaction was carried out without
degassing the toluene solution. In fact, running the
reaction in the presence of oxygen gas resulted in a 90%
yield of the dimer with no trace of either the R-OAcHex
or Bu group transfer products. The dimer could possibly
arise via a radical coupling reaction, or via direct
decomposition of an organocopper intermediate.11 Add-
ing radical inhibitors, TEMPO or galvinoxyl, to the
(6) (a) Farina, V.; Kapadia, S.; Krishnan, B.; Wang, C.; Liebeskind,
L. S. J . Org. Chem. 1994, 59, 5905-5911. (b) Allred, G. D.; Liebeskind,
L. S. J . Am. Chem. Soc. 1996, 118, 2748-2749. (c) Piers, E.; McEach-
ern, E. J .; Burns, P. A. J . Org. Chem. 1995, 60, 2322-2323. (d) Piers,
E.; McEachern, E. J .; Romero, M. A. Tetrahedron Lett. 1996, 37, 1173-
1176.
(7) Some butyl transfer is reported for R-phthaloylalkyl stannanes,
but is not indicated for R-acetoxy stannane reactions in ref 5a. An
interesting observation that carrying out the coupling reaction under
CO favors Bu transfer is indicated in a footnote; however, no dimeric
products (vida infra) are reported.
(8) (a) Linderman, R. J .; Griedel, B. D. J . Org. Chem. 1991, 56,
5491-5493. (b) Linderman, R. J .; Griedel, B. D. J . Org. Chem. 1990,
55, 5428-5430. (c) Linderman, R. J .; Godfrey, A.; Horne, K. Tetrahe-
dron 1989, 45, 495-506 and references therein.
(9) Conditions for the Pd/Cu coupling reactions were typically 4 mol
% Pd(PPh3)2Cl2 and 8 mol % CuCN in refluxing toluene (ref 5a). Other
Pd (Pd(PPh3)4, Pd2(dba)3) and Cu (CuI, CuCl, CuBr) sources and
solvents (THF) were also examined.
(1) (a) Labadie, J . W.; Tueting, D.; Stille, J . K. J . Org. Chem. 1983,
48, 4634-4642. (b) For a review, see: Mitchell, T. N. Synthesis 1992,
803-815. For additional examples of Pd catalyzed nonselective transfer
of an R-alkoxyalkyl group, see: (c) Kosugi, M.; Sumiya, T.; Ogata, T.;
Sano, H.; Migita, T. Chem. Lett. 1984, 1225-1226. (d) Majeed, A. J .;
Antonsen, O.; Benneche, T.; Undheim, K. Tetrahedron 1989, 45, 993-
1006.
(2) Ferezou, J . P.; J ulia, M.; Li, Y.; Liu, W.; Pancrazi, A. Synlett
1991, 53-56.
(3) (a) Vedejs, E.; Haight, A. R.; Moss, W. O. J . Am. Chem. Soc. 1992,
114, 6556-6558. (b) For an internally activated tin hydride reagent,
see: Vedejs, E.; Duncan, S. M.; Haight, A. R. J . Org. Chem. 1993, 58,
3046-3050.
(10) The yields of 2 and 3 are calculated based on 1a . The yield of
4 is based on benzoyl chloride. The molar ratios were determined from
the molar quantities of the isolated products and are therefore
independent of starting material amounts. These data clearly indicate
that dimer formation and Bu transfer are significant in reactions of
stannane 1a .
(4) (a) Linderman, R. J .; Graves, D. M.; Kwochka, W. R.; Ghannam,
A. F.; Anklekar, T. V. J . Am. Chem. Soc. 1990, 112, 7438-7439. (b)
Siedlecki, J . M. Unpublished results.
(5) (a) Ye, J .; Bhatt, R. K.; Falck, J . R. J . Am. Chem. Soc. 1994,
116, 1-5. (b) Ye, J .; Bhatt, R. K.; Falck, J . R. Tetrahedron Lett. 1993,
34, 8007-8010. (c) Falck, J . R.; Bhatt, R. K.; Ye, J . J . Am. Chem. Soc.
1995, 117, 5973-5982.
(11) The presence of oxygen is well known to induce oxidative
coupling of organocopper and -cuprate species. For a recent synthetic
example, see: Lipshutz, B. H.; Siegmann, K.; Garcia, E.; Kayser, F. J .
Am. Chem. Soc. 1993, 115, 9276-9282.
S0022-3263(96)01161-9 CCC: $12.00 © 1996 American Chemical Society

Communications
J . Org. Chem., Vol. 61, No. 19, 1996 6493
Ta ble 1. Cop p er Cya n id e-Ca ta lyzed Cou p lin g Rea ction s
of 1b
Sch em e 1
entry
electrophilea
2, R )b
yield, %
1
2
3
4
5
6
7
8
PhCOCl
CH3COCl
C5H11COCl
iPrCOCl
tBuCOCl
allyl bromide
cinnamyl bromide
iodobenzene
COPh
COCH3
COC5H11
COiPr
COtBu
CH2CHdCH2
CH(Ph)CHdCH2
Ph
2a
2b
2c
2d
2e
2f
78
73c
90
89
92
80c
85d
0e
2g
2h
Two equivalents. See eq 3 for structure of 2. c Four equiva-
a
b
d
lents of RX were used. Obtained as a 1:1.5 diastereomeric
mixture. e 93% recovery of 1b.
only the SN2′ product 2g as a 1:1.5 mixture of diastere-
omers. Reaction of 1b with iodobenzene did not result
in any coupled product 2h . As observed with the tribu-
tyltin species, attempted reactions of the MOM 6b or
MeO 7b derivatives with acid chlorides or allyl bromide
did not provide any coupling products.
reaction mixture led to good yields of the dimer (>65%)
along with a significant decrease in the yield of the
R-OAcHex product. These data support the premise that
an organocopper intermediate is formed. When the
coupling reaction was carried out using only CuCN as
catalyst, similar results were obtained. In this reaction,
the yields of the coupling products were R-OAcHex 2 34%,
dimer 3 26%, and Bu transfer 4 22%. The molar ratio of
isolated 2:3:4 was 44:17:34. The selectivity for R-OAcHex
transfer was slightly enhanced using CuI in place of
CuCN, but the yield of the R-OAcHex coupling product
(30%) was attenuated. The molar ratio of 2:3:4 was 55:
25:11 for the CuI-catalyzed reaction. In agreement with
previous work,2,5 the use of the ether derivatives, MOM
6a or OMe 7a , in the same reaction did not lead to
coupling (R-OAcHex or Bu) products or dimer.
We noted that none of the studies to date had examined
selective transfer of the R-acyloxyalkyl group from a
tetraalkylstannane in which all of the Sn-C bonds were
to secondary carbons. We reasoned that use of a second-
ary alkyl group on tin might eliminate or reduce compet-
ing alkyl group transfer from the R3Sn moiety. Forma-
tion of (R-hydroxyhexyl)tricyclohexyltin was accom-
plished by Cy3SnLi condensation with hexanal (Scheme
1).12 The sensitive free alcohol 5b was protected by
acetylation with acetyl chloride to provide the R-acetoxy
derivative 1b in 95% overall yield. The corresponding
MOM derivative 6b was also prepared in 65% yield.8
Lewis acid-catalyzed reduction of the MOM ether with
Et3SiH then provided the simple methyl ether derivative
7b .8a Reaction of the tricyclohexyl derivative 1b with
benzoyl chloride and catalytic CuCN in toluene provided
the desired coupling product in 78% yield (eq 2). None
of the cyclohexylphenyl ketone 8 was observed, nor was
the dimer 3 noted.13 Results of coupling 1b with aliphatic
acid chlorides and allyl bromides (eq 3) are given in Table
These results indicate that intramolecular activation3
or possible stabilization by sulfur5 is not a prerequisite
for selective (R-acetoxyalkyl) transfer reactions from
nonsymmetric tetraalkylstannanes. The methyl ether
derivatives 7a and 7b can be taken as a baseline value
for 119Sn chemical shifts, -38.1 ppm and -104.0 ppm,
respectively, for a noncomplexed stannane. The MOM
ether derivatives 6a and 6b 119Sn NMR signals, -36.4
ppm and -103.7 ppm, respectively, reveal virtually no
shift relative to the methyl ether. The Bu3Sn acetate 1a
(-26.7 ppm) does show a modest upfield shift relative to
methyl ether 7a , while the Cy3Sn acetate 1b (-99.3 ppm)
upfield shift relative to methyl ether 7b is not as
significant.14 The slight degree of intramolecular inter-
action (intra- vs intermolecular supported by concentra-
tion studies) for 1a compared to 1b might provide a
rationale for Bu transfer. One of the Bu groups could
occupy an apical position in a trigonal bipyramidal Sn
intermediate, and therefore may be activated toward
transmetalation.3a A similar activation of a cyclohexyl
group in 1b appears to be less favorable.
In summary, we have shown that completely selective
transfer of secondary R-acetoxyalkyl groups can occur
from (R-acetoxyhexyl)tricyclohexyltin. In contrast, sev-
eral examples of cross coupling reactions of (R-alkoxy-
alkyl)tributyl- or -methyltin compounds have resulted in
nonselective transfer of both alkyl groups. The data in
the literature and that from our present study indicate
this reaction is complex and is likely dependent on a
number of factors.
Ack n ow led gm en t. J .M.S. thanks the Burroughs
Wellcome Fund and Glaxo for fellowships. Experimen-
tal procedures and spectral data for all new compounds
1a ,b, 2a ,c-g, 3, 6b, 7a ,b, and 8 (27 pages).
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures and spectral data for all new compounds 1a ,b, 2a ,c-
g, 3, 6b, 7a , and 8 (27 pages).
1. The yields of 2 are uniformly high, from 73% for 2b
to 92% for 2e derived from sterically demanding pivaloyl
chloride. The reaction with cinnamyl bromide provided
J O961161H
(14) For a recent paper examining intra- and intermolecular coor-
dination of (alkyl)trichlorostannanes, see: Biesemans, M.; Willem, R.;
Damoun, S.; Geerlings, P.; Lahcini, M.; J aumier, P.; J ousseaume, B.
Organometallics 1996, 15, 2237-2245. 119Sn NMR data for the SnCl3
derivatives typically revealed a >30 ppm upfield shift for complexed
(trigonal bipyramidal at Sn) relative to uncomplexed (tetrahedral at
Sn) species.
(12) For the preparation of Cy3SnLi, see: J ousseaume, B.; Lahcini,
M.; Rascle, M.-C. Organometallics 1995, 14, 685-689.
(13) Phenylcyclohexyl ketone 8 and dimer 3 were prepared inde-
pendently. GC analysis of crude coupling reaction mixtures did not
detect 3 or 8 in reactions using 1b.