Chromium(0)-Promoted [6π + 2π] cycloadditions of allenes with cycloheptatriene

Article abstract of DOI:10.1021/ol802401a

(Chemical Equation Presented) Photoinitiated [6π + 2π] cycloadditions of allenes with (η⁶-cycloheptatriene)tricarbonylchromium(0) (1) are described. An example of asymmetric induction obtained by reaction of 1 with a chiral 1,3-disubstituted al

Full text of DOI:10.1021/ol802401a

ORGANIC
LETTERS
2008
Vol. 10, No. 24
5609-5612
Chromium(0)-Promoted [6π + 2π]
Cycloadditions of Allenes with
Cycloheptatriene
James H. Rigby,* Ste´phane B. Laurent, Zeeshan Kamal, and Mary Jane Heeg†
Department of Chemistry, Wayne State UniVersity, Detroit, Michigan 48202-3489
jhr@chem.wayne.edu
Received October 17, 2008
ABSTRACT
Photoinitiated [6π + 2π] cycloadditions of allenes with (η6-cycloheptatriene)tricarbonylchromium(0) (1) are described. An example of asymmetric
induction obtained by reaction of 1 with a chiral 1,3-disubstituted allene is also reported.
Transition-metal-mediated higher-order cycloaddition reac-
tions have become important synthetic tools for the construc-
tion of medium-sized ring targets.1 In particular, Cr(0)-
promoted [6π + 4π] and [6π + 2π] cycloadditions with
cyclic trienes have been extensively studied in the context
of synthetic applications.2,3 These transformations can be
initiated either photochemically or thermally; however,
photochemical activation appears to be more compatible with
sensitive reaction partners. Thus, isocyanates and ketenes
have been successfully used as 2π partners in the photoin-
duced [6π + 2π] cycloaddition reactions with (cyclohep-
tatriene)tricarbonylchromium(0) (1), whereas they were less
successful under thermal conditions.4 In light of these results,
allenes were viewed as potentially viable 2π partners.
Furthermore, the [6π + 2π] cycloaddition of chiral 1,3-
disubstituted allenes could provide a simple route to optically
active bicyclo[4.2.1]nonane ring systems (Scheme 1). To the
Scheme 1
† To whom inquiries about X-ray structures should be addressed.
(1) (a) Lautens, M.; Klute, W.; Tam, W. Chem. ReV. 1996, 96, 49–92.
(b) Fru¨hauf, H. W. Chem. ReV. 1997, 97, 523–596.
(2) For reviews of Cr(0)-mediated [6π + 4π] and [6π + 2π] cycload-
dition reactions, see: (a) Rigby, J. H. Acc. Chem. Res. 1993, 26, 579–585.
(b) Rigby, J. H. In AdVances in Metal-Organic Chemistry; Liebeskind, L. S.,
Ed.; JAI Press: Greenwich, 1995; Vol. 4, pp 89-127. (c) Rigby, J. H.
best of our knowledge, the metal-mediated [6π + 2π]
cycloaddition of allenes has not been described previously.5
Thermal, metal-free cycloadditions of allenes to cyclic trienes
such as tropone and azaheptafulvenes have been studied, but
Tetrahedron 1999, 55, 4521–4538
.
(3) For synthetic applications of Cr(0)-mediated [6π + 4π] and [6π +
2π] cycloadditions, see: (a) Rigby, J. H. In AdVances in Cycloaddition;
Harmata, M., Ed.; JAI Press: Greenwich, 1999; Vol. 6, pp 97-118. (b)
Rigby, J. H.; Meyer, J. H. Synlett 1999, (Eschenmoser Issue), 860–862. (c)
Rigby, J. H.; Warshakoon, N. C.; Payen, A. J. J. Am. Chem. Soc. 1999,
121, 8237–8245. (d) Rigby, J. H.; Niyaz, N. M. Tetrahedron 2001, 57,
5091–5095. (e) Rigby, J. H.; Niyaz, N. M.; Bazin, B. Tetrahedron 2002,
58, 4879–4885. (f) Rigby, J. H.; Laxmisha, M. S.; Hudson, A. R.; Heap,
(4) Rigby, J. H.; Ahmed, G.; Ferguson, M. D. Tetrahedron Lett. 1993,
34, 5397–5400.
(5) For an overview of cycloadditions of allenes, see: Murakami, M.;
Matsuda, T. In Modern Allene Chemistry; Krause, N., Hashmi, A. S. K.,
Eds.; Wiley-VCH: Weinheim, 2004; pp 727-815.
C. H.; Heeg, M. J. J. Org. Chem. 2004, 69, 6751–6760
.
10.1021/ol802401a CCC: $40.75
Published on Web 11/20/2008
2008 American Chemical Society

Table 1. Photoinitiated [6π + 2π] Cycloaddition Reaction of 1
with 1,1-Disubstituted Allenes 2a-c
Table 2. Photoinitiated [6π + 2π] Cycloaddition Reaction of 1
with 1,3-Disubstituted Allenes 4a-c
entry allene
R1
Ph
R2
procedurea product yield (%)b
isomeric ratioc
yield
1
2
3
2a
2b
2c
H
H
A
B
B
3a
3b
3c
50
51
35
entry allene procedurea product (%)b
5 (E/Z)
6 (E/Z)
(CH2)5
(CH2)5 CH2OTBS
1
2
3
4
4a
4a
4b
4c
A
B
A
B
5a
59 100 (>99:<1)
50 100 (85:15d)
56f 100 (>99:<1)
64 88 (10:90)
0
0
0
a Procedure A: a mixture of 1 (1 equiv) and allene (2 equiv) in hexanes
was irradiated at rt in a pyrex tube for periods of 4-6 h. Procedure B: to
a solution of 1 in hexanes in a pyrex tube was introduced under irradiation
at rt slowly a solution of allene (2 equiv) in hexanes via a syringe pump,
then additional irradiation was continued for 4-6 h. See Supporting
Information for more details. b Yield of isolated product after purification
by flash chromatography.
5a
5be
5c, 6c
12 (23:77)
a See footnote a of Table 1. b Overall yield (5 + 6) of isolated product
after purification. c Ratios (5/6, E/Z) determined by GC analysis on the crude
product before purification. d Sometimes E/Z ∼ 98:2. e Isolated as an alcohol
after removal of the THP group. f Yield over two steps after removal of the
THP group.
only [8 + 2]6 or [4 + 2]7 cycloadducts were isolated
depending on the nature of the allene.
Herein, results of a study on the photoinitiated [6π + 2π]
cycloaddition of allenes with (η6-cycloheptatriene)tricarbo-
nylchromium(0) (1) are reported.
syn coplanar with the (C-8)-(C-1) bond and, consequently,
orientated away from the substituent at C-7.10 Subsequent
X-ray crystallographic analysis performed on a derivative
of 5a (p-nitrobenzoate ester) confirmed the structural and
stereochemical assignments (see Supporting Information).
Surprisingly, when the same cycloaddition was performed
using the “slow addition” technique (procedure B), the Z
isomer of 5a with the phenyl group syn to C-7 could also be
detected (E/Z ) 85:15, entry 2). In rare cases, procedure B
led to the virtually exclusive formation of the E isomer. For
the moment, it is not evident how the rate of slow addition
of allene promotes the formation of the Z isomer. The
cycloaddition with 4b (procedure A) behaved similarly to
the cycloaddition with 4a to give, after deprotection of the
THP group, uniquely the alcohol (E)-endo-5b (56% over two
steps, entry 3). Irradiation of 1 with 4c (procedure B) gave
a 88:12 mixture of regioisomers endo-5c and endo-6c in 64%
overall yield (entry 4). Curiously, cycloaddition also occurred
at the π bond bearing the phenyl group. The high regiose-
lectivity observed when an ether group was present is
consistent with a prior coordination of the oxygen atom to
the chromium center which should favor bond formation at
the π bond bearing the ether substituent. With a methyl
group, no coordination is possible, and the steric effects with
1 would be expected to control regioselectivity. Each of the
regioisomers 5c and 6c was in turn isolated as a mixture of
Z and E isomers. For 5c, the Z isomer with the phenyl group
orientated away from the methyl group at C-7 was found to
be the major isomer in line with previous results (Table 2,
entries 1-3), whereas for the major isomer of 6c, the methyl
group was found to be syn to the phenyl group at C-7.
All of the following cycloaddition reactions were per-
formed in a pyrex reactor with a 450 W Canrad-Hanovia
medium pressure Hg vapor lamp. Two different procedures
were evaluated in the study: (a) a mixture of complex 1 (1
equiv) and allene (2 equiv) in hexanes was directly irradiated
(procedure A); (b) a solution of allene (2 equiv) in hexanes
was added slowly to a solution of 1 in hexanes using a
syringe pump under continuous irradiation (procedure B).
A preliminary experiment was performed with complex 1
and 1,1-diphenyl-1,2-propadiene (2a) following procedure
A. The metal-free [6 + 2]-cycloadduct 3a was obtained in
50% yield as a single regioisomer (Table 1, entry 1). Similar
results were observed with vinylidenecyclohexane (2b) and
trisubstituted allene 2c using procedure B, affording cy-
cloadducts 3b and 3c, respectively, in moderate yields
(entries 2 and 3). In each case, cycloaddition occurred at
the less sterically congested double bond of the 2π partner.
Regioisomer 3c was isolated as a single diastereomer
resulting from an exclusive endo approach of the allene,
paralleling the [6π + 2π] cycloaddition with alkenes.8,9
1,3-Disubstituted allenes were then examined. When allene
4a was employed using procedure A, a single isomer 5a was
obtained in 59% yield (Table 2, entry 1). The addition
occurred exclusively at the unsaturation bearing the
CH2OTBS substituent via an endo transition state. The phenyl
group on the exocyclic double bond in 5a was found to be
(6) (a) Gompper, R.; Wolf, U. Liebigs Ann. Chem. 1979, 1388–1405.
(b) Hayakawa, K.; Nishiyama, H.; Kanematsu, K. J. Org. Chem. 1985, 50,
512–517.
(9) When concerned, the relative configuration of the stereocenter at
the C-7 position was established by 1H NMR NOE difference experi-
ments, and in each case studied, only the endo-cycloadduct was obtained.
See Supporting Information for additional discussion of structural
assignments.
(10) All the E and Z geometries discussed in this study were supported
by 1H NMR NOE correlations. See Supporting Information for some
discussed examples.
(7) (a) Gandhi, R. P.; Ishar, M. P. S. Chem. Lett. 1989, 101–104. (b)
Ishar, M. P. S.; Gandhi, R. P. Tetrahedron 1993, 49, 6729–6740.
(8) (a) Rigby, J. H.; Henshilwood, J. A. J. Am. Chem. Soc. 1991, 113,
5122–5123. (b) Rigby, J. H.; Ateeq, H. S.; Charles, N. R.; Henshilwood,
J. A.; Short, K. M.; Sugathapala, P. M. Tetrahedron 1993, 49, 5495–5506
.
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Org. Lett., Vol. 10, No. 24, 2008

Table 3. Photoinitiated [6π + 2π] Cycloaddition Reaction of 1 with Monosubstituted Allenes 7a-i
isomeric ratioc
8 (Z/E)
entry
R
procedurea
product
yield (%)b
9
1
Ph, 7a
B
8a, 9a
8b, 9b
8c, 9c
8d, 9d
8e
50
>97 (45:55)
>97 (48:52)
>97 (48:52)
>97 (40:60)
100 (65:35)
100 (60:40)
40 (15:85)
40 (35:65)
25 (35:65)
65 (45:55)
65 (40:60)
60 (40:60)
<3
<3
<3
<3
0
2
p-MeOC6H4, 7b
p-EtO2CC6H4, 7c
p-O2NC6H4, 7d
CO2Et, 7e
B
42
3
B
B
23
4
56
5
A or B
Ae or Be
A or B
A or B
B
34d
56d
38
6
CO2Et, 7e
8e
0
7
CH2OTBS, 7f
CH2OTHP, 7g
OMe, 7h
8f, 9f
8gf, 9gf
8h, 9h
8i, 9i
8i, 9i
8i, 9i
60
60
75
35
35
40
8
41g
51
9
10
11
12
OTBS, 7i
A
23h
50h
64h
OTBS, 7i
B
OTBS, 7i
Bi
a See footnote a of Table 1. b Overall yield (8 + 9) of isolated product after flash chromatography. c Ratios (8/9, Z/E) determined by GC analysis on the
crude product before purification or by H NMR. d Adduct 10 (ca. 4% yield) was also formed. e 5 equiv of allene was used. f Isolated as an alcohol after
1
removal of the THP group. g Overall yield over two steps after removal of the THP group. h Tetracycle 11 (5-8% yield) was also isolated. i The reaction
mixture was cooled at 0 °C during irradiation, and additional irradiation was continued for 1 h after addition of allene.
Attention was then directed toward cycloaddition of 1 with
monosubstituted allenes (Table 3). Preliminary experiments
were carried out with aryl allenes 7a-d bearing various
substituents on the phenyl ring. Whenever an arylallene was
used, the cycloaddition (procedure B) afforded the 8-type
regioisomer with excellent selectivity (ratios 8a-d/9a-d >
97:3 by GC analysis of the crude mixtures) and with
moderate yields (entries 1-4). Each regioisomer was isolated
as an inseparable mixture of Z and E isomers in ratios of
50:50. In contrast to the case with 1,3-disubstituted allenes,
the absence of a substituent at the C-7 position in the final
products would reduce steric interactions and would allow
the aryl substituent to be placed syn to C-7 more easily. When
a mixture of 1 and ethyl buta-2,3-dienoate (7e) was irradiated,
the cycloaddition occurred only at the terminal double bond
of the allene to afford the regioisomer 8e as a separable 65:
35 mixture of Z and E isomers in 34% yield (entry 5). No
addition to the electron-deficient double bond of the allene
was observed. This result is in stark contrast to that obtained
in the [6π + 2π] cycloaddition with alkenes in which only
electron-deficient alkenes participate in the cycloaddition
process.8a It is also noteworthy that 8e isomerizes during
the reaction to give 10 (ca. 4%). The yield of 8e could be
dramatically improved by using 5 equiv of allene instead of
the usual 2 equiv (entry 6). Irradiation of 1 with protected
buta-2,3-dienol (7f) (procedure A or B) yielded a separable
40:60 mixture of regioisomers 8f and endo-9f in 38% overall
yield (entry 7). In contrast to the cycloadditions with
arylallenes or allenic ester 7e, there was a slight preference
for reaction at the internal double bond of the allene. This
might be explained by a prior coordination of the oxygen
atom of the ether group to the metal center, which would
favor attack at the substituted double bond. A similar
behavior was observed when 7g was examined (entry 8).
Cycloaddition of 1 with methoxyallene (7h) (procedure B)
took place preferentially at the internal and electron-rich
double bond of the allene, to give a 25:75 mixture of 8h
and endo-9h in a 51% overall yield (entry 9). When the
bulkier alkoxyallene 7i was engaged, the regioselectivity of
the cycloaddition was found to reverse relative to the
cycloaddition with 7h, giving mixtures of 8i and endo-9i in
60-65:40-35 ratios (entries 10-12). This reversal might
be due to the presence of the bulky TBS group, which would
disfavor approach of the allene from the internal double bond.
An optimum overall reaction yield of 64% was obtained
when reaction was performed at 0 °C using procedure B
(entry 12). It is also noteworthy that the Z/E selectivity for
8-type adducts was the same when 1-alkoxypropa-1,2-dienes
7h,i or 4-alkoxybuta-1,2-dienes 7f,g were employed (sub-
stituent preferentially syn to C-7), whereas it was reversed
when electron-deficient allene 7e was used (substituent
preferentially anti to C-7).
In the reactions that gave cycloadducts 8i and 9i, a new
adduct identified as the tetracyclic 11 was also isolated as a
single diastereomer (5-8%, Table 3, entries 10-12). The
structure of 11 was unambiguously established by analysis
of 1D and 2D NMR data (1H, 13C, Dept, COSY, HMQC,
Homodecoupling, INADEQUATE, and NOE sequences). A
final confirmation of the structural and stereochemical
assignment was provided by an X-ray crystallographic
analysis performed on its diol derivative (see Supporting
Information). This structure appears to be novel and might
arise from a second Cr(0)-mediated [6π + 2π] cycloaddition
between cycloadduct 9i and allene 7i (Scheme 2). Such a
tandem cycloaddition process has precedent in metal-
Org. Lett., Vol. 10, No. 24, 2008
5611

protecting TBS group gave the optically active alcohol 5b
in 54% ( 5% ee,12 demonstrating a good transfer of the
chiral information from the allene (Scheme 4).
Scheme 2
Scheme 4. [6 + 2] Cycloaddition of 1 with (S)-4a
mediated cycloaddition.11 Work is currently in progress to
identify conditions that would favor the formation of this
tetracyclic core and to obtain a better understanding of this
unusual transformation.
Finally, to evaluate asymmetric induction in the [6 + 2]
cycloaddition, a preliminary investigation was performed
with a chiral, nonracemic allene.
Chiral propargylic alcohol (R)-13 was prepared in 31%
yield and 88% ( 5% ee12 via enantioselective addition of
terminal alkyne 12 to benzaldehyde using a procedure
described by Carreira13 (Scheme 3). Compound (R)-13 was
In summary, we have validated the first Cr(0)-mediated
[6π + 2π] cycloaddition of allenes with cycloheptatriene
under photochemical activation and demonstrated its potential
by constructing an enantioenriched bicyclo[4.2.1]nonane
framework starting from a chiral allene. Regiochemistry and
E/Z selectivity in this cycloaddition were found to be subtly
dependent on competing steric and electronic effects of the
allene substituents. Further studies of this cycloaddition and
investigation of synthetic applications are currently under-
way.
Scheme 3. Preparation of Chiral (S)-4a
Acknowledgment. The authors would like to thank the
National Institutes of Health (GM-30771) for their generous
financial support of this research. We are grateful to Dr. B.
Ksebati for performing the NOE, homodecoupling, and
INADEQUATE experiments.
then converted to allene (S)-4a (33%, 60% ( 5% ee) in a
two-step one-pot process.14 The enantiomeric excess was
determined by 1H NMR using a chiral shift reagent (Ag(fod)-
Yb(tfc)3).15
Irradiation of 1 with (S)-4a using procedure A afforded
cycloadduct (E)-5a (45%). Subsequent removal of the
Supporting Information Available: Experimental pro-
cedures, full characterization data, 1H and 13C NMR spectra
for all new compounds, and NOE descriptions and X-ray
data (CIF). This material is available free of charge via the
Internet at http://pubs.acs.org.
OL802401A
(11) Related Cr(0)-mediated tandem [6π + 2π], homo[6π + 2π]
cycloadditions of alkynes with cyclic trienes are reported in the literature:
(a) Rigby, J. H.; Warshakoon, N. C.; Heeg, M. J. J. Am. Chem. Soc. 1996,
118, 6094–6095. (b) Chen, W.; Chaffee, K.; Chung, H. J.; Sheridan, J. B.
J. Am. Chem. Soc. 1996, 118, 9980–9981. (c) Rigby, J. H.; Heap, C. R.;
Warshakoon, N. C.; Heeg, M. J. Org. Lett. 1999, 1, 507–508. (d) Rigby,
J. H.; Heap, C. R.; Warshakoon, N. C. Tetrahedron 2000, 56, 2305–2311.
(e) Ref 3f.
(12) ee was determined by 1H NMR after conversion to the Mosher
ester (see Supporting Information).
(13) Boyall, D.; Frantz, D. E.; Carreira, E. M. Org. Lett. 2002, 4, 2605–
2606, and references cited therein.
(14) Konoike, T.; Araki, Y. Tetrahedron Lett. 1992, 33, 5093–5096.
(15) Mannschreck, A.; Munninger, W.; Burgemeister, T.; Gore, J.; Cazes,
B. Tetrahedron 1986, 42, 399–408. See Supporting Information.
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Org. Lett., Vol. 10, No. 24, 2008