Chromium-catalyzed radical cyclization of bromo and chloro acetals

Article abstract of DOI:10.1021/om101068r

Cyclopentadienyl chromium β-diketiminate catalysts are used for the radical cyclization of bromo and chloro acetals. Mn powder activated with PbBr₂ or PbCl₂ is the stoichiometric reductant, and γ-terpinene is the hydrogen atom donor.

Full text of DOI:10.1021/om101068r

Organometallics 2010, 29, 6639–6641 6639
DOI: 10.1021/om101068r
Chromium-Catalyzed Radical Cyclization of Bromo and Chloro Acetals
K. Cory MacLeod,† Brian O. Patrick,‡ and Kevin M. Smith*,†
†Department of Chemistry, University of British Columbia Okanagan, 3333 University Way, Kelowna, BC, Canada
V1V 1V7, and ‡Department of Chemistry, University of British Columbia, Vancouver, BC, Canada V6T 1Z1
Received November 12, 2010
Summary: Cyclopentadienyl chromium β-diketiminate cata-
lysts are used for the radical cyclization of bromo and chloro
acetals. Mn powder activated with PbBr2 or PbCl2 is the stoichio-
metric reductant, and γ-terpinene is the hydrogen atom donor.
Although the primary cyclized product can be isolated and struc-
turally characterized as the Cr(III) complex, this substrate can
also be reduced catalytically under mild photolysis conditions.
bond dissociation energy can be controlled by changing the
ancillary ligands.10 Although Cr(III) lacks the extensive
biochemistry of organocobalt complexes,11 we wish to ex-
plore the M-R homolysis reactivity of well-defined chro-
mium complexes.
The radical cyclization of halo acetals (Ueno-Stork reac-
tion)12 has been used to explore new radical-based methodo-
logy.13 The reaction products are useful precursors for synth-
esis, and the starting materials are readily prepared from the
appropriate enol ether, allyl alcohol, and N-halosuccinimide.
Transition-metal-mediated reactions typically employ the iodo
acetals or the more stable bromo acetals.14 Oshima and co-
workers have reported radical cyclization reactions with zirco-
nocene-based reagents that are catalytic for bromo acetals and
stoichiometric for chloro acetals.15
The reversible generation of organic radicals has been pro-
posed as a key feature in several new carbon-carbon bond-
forming reactions catalyzed by first-row transition metals.1 The
same reactivity mode is the foundation for transition-metal-
mediated controlled radical polymerization.2 We previously re-
ported that the radical polymerization of vinyl acetate could be
initiated and controlled using a well-defined Cr(III) alkyl com-
plex3 and investigated how the rate of Cr-R homolysis could be
modified through steric interactions.4 We would now like to
report the use of the same CpCr[(XylNCMe)2CH] system for the
intramolecular radical cyclization of bromo and chloro acetals.
For decades, the biological chemistry of vitamin B12 has
guided the study of reversible metal-alkyl bond homolysis.
Organocobalt complexes with simple, readily modified Schiff
base ligands exhibit the critical Co(III)-alkyl and Co(III)-
hydride homolysis reactivity.5 Once the mechanism had been
established,6 these synthetic complexes could be applied in
the controlled radical polymerization and oligomerization of
activated olefins,7 as catalysts for H2 production,8 and as
reagents for organic synthesis.9 In each case, the key Co-R
*Corresponding author. E-mail: kevin.m.smith@ubc.ca.
(1) Rudolph, A.; Lautens, M. Angew. Chem., Int. Ed. 2009, 48, 2656–2670.
(2) (a) Poli, R. Angew. Chem., Int. Ed. 2006, 45, 5058–5070. (b) Ouchi,
M.; Terashima, T.; Sawamoto, M. Chem. Rev. 2009, 109, 4963–5050. (c)
Smith, K. M.; McNeil, W. S.; Abd-El-Aziz, A. S. Macromol. Chem. Phys.
2010, 211, 10–16. (d) di Lena, F.; Matyjaszewski, K. Prog. Polym. Sci.
2010, 35, 959–1021.
(3) Champouret, Y.; MacLeod, K. C.; Baisch, U.; Patrick, B. O.;
Smith, K. M.; Poli, R. Organometallics 2010, 29, 167–176.
(4) MacLeod, K. C.; Conway, J. L.; Patrick, B. O.; Smith, K. M. J.
Am. Chem. Soc. ASAP (DOI: 10.1021/ja1083392).
Chromium(III) alkyl complexes are readily generated by
the single-electron oxidative addition of Cr(II) with organic
(10) (a) Fryzuk, M. D.; Leznoff, D. B.; Thompson, R. C.; Rettig, S. J. J.
Am. Chem. Soc. 1998, 120, 10126–10135. (b) Langlotz, B. K.; Fillol, J. L.; Gross,
J. H.; Wadepohl, H.; Gade, L. H. Chem.-Eur. J. 2008, 14, 10267–10279. (c)
Dutta, G.; Kumar, K.; Gupta, B. D. Organometallics 2009, 28, 3485–3491.
(11) Vincent, J. Dalton Trans. 2010, 39, 3787–3794.
(12) (a) Ueno, Y.; Chino, K.; Watanabe, M.; Moriya, O.; Okawara,
M. J. Am. Chem. Soc. 1982, 104, 5564–5566. (b) Stork, G.; Mook, R., Jr.;
Biller, S. A.; Rychnovsky, S. D. J. Am. Chem. Soc. 1983, 105, 3741–3742.
(5) Schrauzer, G. N. Acc. Chem. Res. 1968, 1, 97–103.
ꢀ ꢁ
(6) (a) Halpern, J. Acc. Chem. Res. 1982, 15, 238–244. (b) Samsel,
E. G.; Kochi, J. K. J. Am. Chem. Soc. 1986, 108, 4790–4804. (c) Daikh,
B. E.; Finke, R. G. J. Am. Chem. Soc. 1992, 114, 2938–2943.
(7) (a) Gridnev, A. A.; Ittel, S. D. Chem. Rev. 2001, 101, 3611–3659.
(13) Salom-Roig, X. J.; Denes, F.; Renaud, P. Synthesis 2004, 1903–1928.
(14) (a) Vaupel, A.; Knochel, P. J. Org. Chem. 1996, 61, 5743–5753. (b)
~
ꢀ
Phapale, V. B.; Bunuel, E.; García-Iglesias, M.; Cardenas, D. J. Angew. Chem.,
Int. Ed. 2007, 46, 8790–8795. (c) Wakabayashi, K.; Yorimitsu, H.; Oshima, K. J.
Am. Chem. Soc. 2001, 123, 5374–5375. (d) Ohmiya, H.; Yorimitsu, H.; Oshima,
K. J. Am. Chem. Soc. 2006, 128, 1886–1889. (e) Affo, W.; Ohmiya, H.; Fujioka,
T.; Ikeda, Y.; Nakamura, T.; Yorimitsu, H.; Oshima, K.; Imamura, Y.; Mizuta, T.;
Miyoshi, K. J. Am. Chem. Soc. 2006, 128, 8068–8077. (f) Someya, H.; Kondoh,
A.; Sato, A.; Ohmiya, H.; Yorimitsu, H.; Oshima, K. Synlett 2006, 3061–3064.
(g) Zhou, L.; Hirao, T. J. Org. Chem. 2003, 68, 1633–1635. (h) F€urstner, A.;
Martin, R.; Krause, H.; Seidel, G.; Goddard, R.; Lehmann, C. W. J. Am. Chem.
Soc. 2008, 130, 8773–8787.
ꢀ ^
ꢀ ^
(b) Debuigne, A.; Poli, R.; Jerome, C.; Jerome, R.; Detrembleur, C. Prog.
Polym. Sci. 2009, 34, 211–239. (c) Sherwood, R. K.; Kent, C. L.; Patrick,
B. O.; McNeil, W. S. Chem. Commun. 2010, 46, 2456–2458.
(8) (a) Hu, X.; Brunschwig, B. S.; Peters, J. C. J. Am. Chem. Soc. 2007,
129, 8988–8998. (b) Dempsey, J. L.; Brunschwig, B. S.; Winkler, J. R.; Gray,
H. B. Acc. Chem. Res. 2009, 42, 1995–2004.
(9) (a) Okabe, M.; Tada, M. J. Org. Chem. 1982, 47, 5382–5384. (b)
€
Giese, B.; Erdmann, P.; Gobel, T.; Springer, R. Tetrahedron Lett. 1992, 33,
4545–4548. (c) Braunchaud, B. P.; Yu, G.-X. Organometallics 1993, 12,
4262–4264. (d) Johnson, M. D. Acc. Chem. Res. 1983, 16, 343–349. (e)
Pattenden, G. Chem. Soc. Rev. 1988, 17, 361–382. (f) Iqbal, J.; Bhatla, B.;
Nayyar, N. K. Chem. Rev. 1994, 94, 519–564. (g) Cahiez, G.; Moyeux, A.
Chem. Rev. 2010, 110, 1435–1462.
(15) (a) Fujita, K.; Nakamura, T.; Yorimitsu, H.; Oshima, K. J. Am.
Chem. Soc. 2001, 123, 3137–3138. (b) Fujita, K.; Yorimitsu, H.; Oshima, K.
Synlett 2002, 337–339. (c) Fujita, K.; Yorimitsu, H.; Oshima, K. Bull. Chem.
Soc. Jpn. 2004, 77, 1727–1736. (d) Fujita, K.; Yorimitsu, H.; Oshima, K.
Chem. Rec. 2004, 4, 110–119.
r
2010 American Chemical Society
Published on Web 11/24/2010
pubs.acs.org/Organometallics

6640 Organometallics, Vol. 29, No. 24, 2010
MacLeod et al.
Figure 1. Thermal ellipsoid diagram (50%) of 3. Only one
isomer of the alkyl ligand is shown, and all H atoms are omitted
for clarity.
halides.16 We recently prepared CpCr[(XylNCMe)2CH](CH2-
SiMe3) in high yield from the oxidative addition of Me3SiCH2I
with CpCr[(XylNCMe)2CH] (1) using an excess of Mn powder
to selectively convert the Cr(III) halide product back to the
reactive Cr(II) complex.4 A similar reaction of 1 and bromo
acetal 2a resulted in the Cr(III) alkyl complex 3 (eq 1). Single
crystals of 3 contain a cocrystallized mixture of one of the
diastereomeric pairs of the cyclized product: the X-ray crystal
structure of 3 is shown in Figure 1.
Figure 2. Steric hindrance and Cr-R homolysis in Cr(III) alkyl
complexes: [Cr] = CpCr[(XylNCMe)2CH].
and reduction of the bromo acetals was achieved using Mn
powder,16a γ-terpinene as hydrogen atom donor,20 PbBr2,21 and
2 mol % bromo complex 4a at 50 °C in THF, as shown
in eq 2. No product was obtained in the absence of chromium
catalyst 4a, consistent with the expected low activity of Mn
powder toward alkyl bromides.22
The synthesis and stability of bicyclic alkyl complex 3
is consistent with our previous mechanistic proposals for this
system. Although the trapping of carbon-based radicals with
Cr(II) is typically rapid and irreversible, Cr(III)-alkyl bond
homolysis can be induced through adverse steric interactions.4,17
The steric discrimination displayed by the CpCr[(XylNCMe)2-
CH] system is remarkably subtle, as demonstrated by the
dramatic difference in homolysis rates observed between the
Cr(III) neopentyl and isobutyl complexes (Figure 2A).4 Simi-
larly, the decrease in the rate of chain growth in the controlled
radical polymerization of vinyl acetate initiated by CpCr-
[(XylNCMe)2CH](CH2CMe3) was attributed to the diminished
propensity of homolysis of the primary alkyl radical resulting
from 2,1-insertion (Figure 2B).3 Bromine atom abstraction from
bromo acetal 2a generates a secondary alkyl radical: intermolec-
ular trapping of this radical by Cr(II) does not compete with the
rapid intermolecular cyclization reaction. However, the primary
alkyl radical of the cyclized product is unhindered enough to
form thermally stable Cr(III) alkyl complex 3 (Figure 2C).
The Cr(III)-alkyl bond strength in the cyclized product may
be attenuated through increased steric hindrance. Reaction of
3,4-dihydro-2H-pyran with NBS and substituted allyl alcohols
provides the bromo acetal substrates 5a-7a, shown in eq 2. The
Cr(III) bromo complex 4a was prepared by single-electron
oxidation of 1with PbBr2,18 as previously reported for the corre-
sponding 2,6-iPr2C6H3-substituted derivative.19 The cyclization
The reduced bicyclic products 10 and 11 were obtained in
good yields, with observed diastereomeric ratios consistent with
those previously reported for these radical cyclizations (Table 1,
entries 2 and 3). The lower yield of 12 (Table 1, entry 4) is
attributed to the electronic stabilization of the radical formed
upon cyclization of 7a. The less reactive secondary benzylic
radical is not as efficiently trapped by the H-atom donor
γ-terpinene, leading to unwanted side reactions.9b,20a Bromo
acetal 8a, prepared from a substituted propargyl alcohol, is also
successfully cyclized and reduced to 13 under the catalytic
reaction conditions (Table 1, entry 5).
The development of reactive yet selective catalysts to activate
the strong C-Cl bonds of organic chlorides has been an ongoing
challenge for organometallic chemists.14h,15,23 Gratifyingly, our
catalytic conditions proved capable of also reducing chloro
€
(16) (a) Furstner, A. Chem. Rev. 1999, 99, 991–1045. (b) Smith, K. M.
Coord. Chem. Rev. 2006, 250, 1023–1031.
(17) (a) Espenson, J. H. Prog. Inorg. Chem. 1983, 30, 189–212. (b)
Wessjohann, L. A.; Schmidt, G.; Schrekker, H. S. Tetrahedron 2008, 64,
2134–2142.
(18) Luinstra, G. A.; Teuben, J. H. J. Chem. Soc., Chem. Commun.
1990, 1470–1471.
(21) Addition of a sub-stoichiometric amount of PbBr2 was found to
accelerate the reduction of Cr(III) bromide 4a with Mn powder to form
Cr(II) complex 1. For studies by Takai and co-workers on the use of
catalytic PbCl2 to activate managanese metal, see: Takai, K.; Ueda, T.;
Hayashi, T.; Moriwake, T. Tetrahedron Lett. 1996, 37, 7049–7052.
(22) (a) Barczak, N. T.; Jarvo, E. R. Eur. J. Org. Chem. 2008, 5507–
5510. (b) Layfield, R. A. Chem. Soc. Rev. 2008, 37, 1098–1107. (c) Cahiez,
G.; Duplais, C.; Buendia, J. Chem. Rev. 2009, 109, 1434–1476. (d) Everson,
D. A.; Shrestha, R.; Weix, D. J. J. Am. Chem. Soc. 2010, 132, 920–921.
(23) (a) Martin, R.; Buchwald, S. L. Acc. Chem. Res. 2008, 41, 1461–
1473. (b) Fu, G. C. Acc. Chem. Res. 2008, 41, 1555–1564. (c) Kliegman, S.;
McNeill, K. Dalton Trans. 2008, 4191–4201. (d) Zhu, D.; Budzelaar,
P. H. M. Organometallics 2010, 29, 5759-5761.
(19) Doherty, J. C.; Ballem, K. H. D.; Patrick, B. O.; Smith, K. M.
Organometallics 2004, 23, 1487–1489.
€
(20) (a) Gansauer, A.; Fleckhaus, A.; Lafont, M. A.; Okkel, A.;
Kotsis, K.; Anoop, A.; Neese, F. J. Am. Chem. Soc. 2009, 131, 16989–
€
16999. (b) Gansauer, A.; Shi, L.; Otte, M. J. Am. Chem. Soc. 2010, 132,
11858–11859. (c) Warren, J. J.; Tronic, T. A.; Mayer, J. M. Chem. Rev.
ASAP (doi: 10.1021/cr100085k).

Communication
Organometallics, Vol. 29, No. 24, 2010 6641
Table 1. Chromium-Catalyzed Radical Cyclization of Bromo and
Chloro Acetalsa
knowledge, this is the first catalytic Ueno-Stork reaction of
chloro acetals.24
When the homolysis reactions shown in Figure 2A were
investigated, previously unappreciated photolytic Cr(III)-R
homolysis reactivity became evident.4 We were interested in
using photolysis to induce catalytic turnovers for cyclized
products that lacked signficant steric bulk. Reaction of 2a under
the standard catalytic conditions in the absence of light was
unsuccessful, with 73% unreacted starting material isolated after
38.5 h. When the catalytic reaction of 2a was performed under
the light of a 23 W household compact fluorescent bulb, the
cyclized product 9was obtained in 48% yield (Table 1, entry 11).
Modulating M-R bond homolysis is critical in metal-
mediated radical chemistry for both synthetic organic and con-
trolled radical poymerization applications. This is particularly
evident when extending radical reactivity to more challenging
substrates. The reactivity features that made CpCr[(XylNC-
Me)2CH](R) complexes suitable for vinyl acetate polymeriza-
tion (efficient trapping of alkyl radicals by Cr(II), absence of
β-hydrogen elimination, sensitivity of Cr(III)-R homolysis to
steric interactions) translate smoothly to the Ueno-Stork reac-
tion. Tin-free reduction of substituted bromo or chloro acetals
can be performed with low catalyst loadings of Cr(III) halide
complex 4a or 4b. The thermal catalytic reaction with the
unsubstituted allyl substrate 2a is unsuccessful, presumably
due to the Cr(III)-R bond strength in 3. However, the process
can be rendered catalytic with mild photolysis. The lower yields
with the chloro acetal substrates may be attributable to the
slower reaction of Cr(II) with the stronger C-Cl bond. We are
currently developing CpCr(LX) complexes with enhanced sin-
gle-electron oxidative addition reactivity to address this issue.
a Substrate (1 mmol). b When X = Br: 4a (2 mol %), PbBr2 (e1 mol %),
38.5 h at 50 °C; X = Cl: 4b (20 mol %), PbCl2 (e1 mol %), 88 h at 70 °C.
c Isolated yields. Diastereomeric ratios are in parentheses. d Isolated 73% of
unreacted starting material 2a. e Mn (5 equiv) and γ-terpinene (5 equiv) were
used. f Mn (4 equiv) was used. g γ-Terpinene (8 equiv) was used. h Ten-day
reaction time. i Performed with a 23 W compact fluorescent light bulb 10 cm
from the reaction vessel.
Acknowledgment. We are grateful to the Natural
Sciences and Engineering Research Council of Canada
(NSERC), the Canadian Foundation for Innovation, and
the University of British Columbia for financial support.
Supporting Information Available: Crystallographic data for
3, complete experimental details, and characterization data. This
material is available free of charge via the Internet at http://pubs.
acs.org.
acetals 5b-8b, albeit with higher catalyst loading (20 mol %)
of CpCr[(XylNCMe)2CH]Cl (4b)3 and lower yields (Table 1,
entries 6-9). The standard reaction time used for comparing
substrates was 88 h, affording yields of 29-57%. With an
increased reaction time of 10 days the yield of 10 from 5b
improved to 70% (Table 1, entry 10). To the best of our
(24) For the radical cyclization of the prenyl ether of 2-chlorophenol
with a cobalt catalyst, see ref 14e.