Gold-catalyzed diastereoselective [2+2+2]-cycloaddition of 1,7-enynes with carbonyl compounds

Article abstract of DOI:10.1039/c2cc36219h

We report a gold-catalyzed [2+2+2]-cycloaddition of 1,7-enynes with carbonyl species; our experimental data suggest that the resulting oxacyclic cycloadducts arose from an interception of gold-containing cyclobutenium intermediates with carbonyl species.

Full text of DOI:10.1039/c2cc36219h

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Gold-Catalyzed Diastereoselective [2+2+2]-Cycloaddition of 1,7-Enynes
with Carbonyl Compounds
Deepak B. Huple and Rai-Shung Liu*
5
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
DOI: 10.1039/b000000x
Abstract: We report a gold-catalyzed [2+2+2]-cycloaddition of
1,7-enyne with carbonyl species; our experimental data
50
10 suggests that the resulting oxacyclic cycloadducts arose from
an interception of gold-containing cyclobutenium
intermediates with carbonyl species.
In the presence of gold and platinum catalysts, 1,nꢀenynes (n = 5ꢀ
7) undergo cycloisomerizations with skeletal rearrangement,
15 giving various carbocycles with high chemoselectivity.1,2 For 1,6ꢀ
terminal enynes I, their key cyclopropyl goldꢀcarbene
intermediates A have a dipole character to react with suitable
dipolarophiles to access bicyclic compounds II.3ꢀ6 The first
realization of this valuable cycloaddition was reported by
20 Echavarren et. al.3 on the goldꢀcatalyzed cyclizations of 1,6ꢀ
enynes bearing a tethered carbonyl functionality (NuꢀE =
R1R2CO); this method has been applied to the total synthesis of
naturally occurring compounds englerin A and B.4
55
Scheme 1. [2+2+2]ꢀCycloadditions of 1,7ꢀenynes with carbonyls.
60 convertible to acyclic diene III in this catalytic system. Our
experimental results suggest that cycloadduct 2 is generated with
an interception of cyclobuteneꢀlike cationic intermediate B with a
carbonyl species, and its formation is unrelated to both
cyclobutenes 3 and acyclic dienes III.
65
Table 1 shows our efforts to realize the cycloaddition of 1,7ꢀ
enyne 1a with benzaldehyde with commonly used gold and
platinum catalysts. An optimized operation involves a slow
addition (2 h) of a metal catalyst in dichloromethane to a mixture
of 1,7ꢀenyne (1 equiv) and benzaldehyde (2 equiv) in hot DCM
25
70 (35 oC). Workup of the solution followed immediately the end of
the catalyst addition. Such an atypical addition drastically
decreases the yields of cycloisomerization product 3a for most
catalysts, but the reason for this phenomenon is still unclear. We
first tested the reactions on P(tꢀBu)2(oꢀbiphenyl)AuNTf2 (entry 1)
75 that gave desired oxacyclic adduct 2a in 81% yield together with
byproduct 3a (14% yield). With a standard reagent addition, we
obtained cycloisomerization product 3a in 88% yield with
cycloadduct 2a in a tractable proportion (2%). For IPrAuNTf2
(IPr = 1,3ꢀbis(diisopropyl phenylimidazolꢀ2ꢀylidene, entry 2), we
In contrast, goldꢀcatalyzed intermolecular cycloadditions of
1,nꢀenynes with carbonyl species still remain a formidable task.
30 With 1,6ꢀenynes, Echavarren attempted to intercept intermediate
A using external carbonyl compounds,5 but the reactions were
inevitably accompanied with side products in significant
proportions. Helmchen studied6 similar cycloadditions using
unsubstituted 1,6ꢀenynes, but carbonyl substrates were few and
35 used in large proportion (20 equiv). To continue our work on
goldꢀcatalyzed cycloadditions on 1,nꢀenynes,7,8 we report an
efficient intermolecular [2+2+2]ꢀcycloaddition of 1,7ꢀenynes 1
with carbonyl species, giving cycloadducts 2 stereoselectively;
herein, the side reaction is the occurrence of cycloisomerization
40 product,9 i.e., bicyclic cyclobutene species 3 that is not
0
80 recovered starting 1a exclusively in hot DCM (35 C, 6 h, entry
2). The reaction chemoselectivity was further improved with
more acidic P(tꢀBu)2(oꢀbiphenyl)AuSbF6 to give oxacyclic adduct
2a in 85% yield. PPh3AuSbF6 also showed
a
fair
chemoselectivity to give compounds 2a and 3a in 71% and 20%
85 yields respectively (entry 4). A control experiment revealed that
AgSbF6 alone gave mainly cycloisomerization species 3a in 60%
yield together with cycloadduct 2a in minor proportion (32%,
entry 5). For AuCl3 and PtCl2/CO, their catalytic reactions gave
mainly undesired cycloisomerization product 3a in 90% and 47%
Department of Chemistry, National Tsing-Hua University, Hsinchu,
Taiwan, ROC E-mail: rsliu@mx.nthu.edu.tw
† Electronic Supplementary Information (ESI) available: Experimental
45 Procedures and characterization data for new compounds.CCDC 876013.
For ESI see DOI:
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55
60
5
65
10
L = P(tꢀBu)2(oꢀbiphenyl), DCM = dichloromethane. 1a (1 equiv., 0.01
a
b
M). PhCHO (2 equiv for entries 1ꢀ7). Yields are obtained after
c
separation from a silica column. The values in parenthesis correspond to
a
d
L = P(tꢀBu)2(oꢀbiphenyl), DCM = dichloromethane, [1a] = 0.01 M.
15 a normal reagent treatment; the reaction duration is 5 min. This yield is
given in the absence of benzaldehyde.
b
c
70 Product yields are obtained after separation from a silica column.
Cyclobutene species 3i was obtained in 31% yield. dPhCHO (6 equiv).
yields respectively (entries 6ꢀ7). In the absence of benzaldehyde,
P(tꢀBu)2(oꢀbiphenyl)AuSbF6 gave only cyclobutene derivative 3a
20 in 90% yield. The molecular structure of compound 2a was
confirmed by xꢀray diffraction study.10
3ꢀfuranyl and 2ꢀthienyl) gave expected oxacycles 4iꢀ4k in 81ꢀ
87% yields (entries 8ꢀ10). To our pleasure, these cycloadditions
75 worked well not only for alkenyl aldehydes but also for acetone;
resulting oxacyclic products 4l and 4m were obtained in 84% and
78% yields respectively (entries 12ꢀ13).
According to our control experiments, oxacyclic cycloadduct
2a was not produced from the goldꢀcatalyzed cycloaddition of
80 bicyclic cyclobutene 3a with benzaldehyde.11 Like other 1,7ꢀ
enynes,9 an acyclic diene such as IIIh (eq 2) was unattainable in
our catalytic system. To assure its absence, we prepared an
We prepared various 1,7ꢀenynes 1bꢀ1i to test the scope of
substrates; their cycloadditions with benzaldehyde (2 equiv) were
operated according to the preceding procedure. We obtained
25 cycloadducts 2bꢀ2i nearly exclusively except entry 8 that gave
cyclobutene compound 3i in a small proportion (31%). For 1,7ꢀ
enyne 1b bearing a cyclopentylidene moiety, we obtained its
resulting oxacycle 2b in 80% yield. The goldꢀcatalyzed
cycloadditions also worked for 1,7ꢀenynes 1cꢀ1g bearing fluoro
30 and methoxy at the phenyl C(3)ꢀC(5) carbons, giving resulting
cycloadducts 2cꢀ2g in 55ꢀ85% yields (entries 2ꢀ6). The reaction
also worked well with allꢀcarbon 1,7ꢀenyne 1h bearing a
methylene bridge (X = CH2, entry 7), producing compound 2h in
78% yield. The cycloaddition on nitrogenꢀbridged 1,7ꢀenyne 1i
35 gave cycloadduct 2i and cycloisomerization product 3i in 41%
and 31% yields respectively. The yield of desired cycloadduct 2i
was increased to 72% using benzaldehyde in excess proportion (6
equiv, entry 8).
We next investigated the scope of aldehydes (2 equiv) and
40 ketones (6 equiv.); the results are provided in Table 3. We
examined the reactions on various 4ꢀsubstituted benzaldehydes;
satisfactory yields (86ꢀ88%) were obtained for methoxyꢀ and
methyl derivatives 4a and 4b (entries 1ꢀ2) whereas decreased
yields (45ꢀ65%) were found for compounds 4c and 4d bearing X
45 = Cl, CO2Me. In entry 4 (X = CO2Me), we obtained also
cycloisomerization byproduct 3a in 35% yield. These reactions
were extensible to various aliphatic aldehydes (Rs = H) including
RL = methyl, ethyl, cyclopropyl and cyclohexyl; their resulting
cycloadducts 4eꢀ4h were produced in satisfactory yields (71ꢀ
50 82%, entries 5ꢀ8). The cycloadditions of heteroaryl aldehydes (RL
= 2ꢀ,
Table 3. [2+2+2]-Cycloadditions with varios carbonyl species
5 mol %
LAuCl/AgsbF6
O
O
Rs
RL
+
+
DCM, 35 0
2 h
C
RL
Rs
O
O
O
c
1aa
2 equiv
4a-mb
3a
O
O
O
R
Ar
85
O
X
O
O
(9) Ar = 2-furanyl (4i, 81%)
(10) Ar = 3-furanyl (4j, 87%)
(11) Ar = 2-thienyl (4k, 81%)
(1) X = OMe (4a, 88%)
(2) X = Me (4b, 86%)
(3) X = Cl (4c, 65%)
(5) R = Me (4e, 82%)
(6) R = Et (4f, 76%)
(7) R = cyclopropyl (4g, 72%)
(4) X = CO2Me (4d, 45%)d (8) R = cyclohexyl (4h, 71%)
O
O
O
Ph
O
(13) 4m (78%)e
(12) 4l (84%)
a
L = P(tꢀBu)2(oꢀbiphenyl), DCM = dichloromethane, [1a] = 0.01 M.
b
c
90 Product yields are obtained after separation from a silica column.
d
aldehyde. Cyclobutene species 3a was obtained in 35%. Acetone (6
equiv).
2
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7671ꢀ7673; (d) A. S. K. Hashmi, L. Ding, J. W. Bats, P. Fischer, W.
authentic sample of acyclic diene IIIh from a separate procedure
Frey, Chem. Eur. J. 2003, 9, 4339ꢀ4345; (e) L. Zhang, S. A.
Kozmin, J. Am. Chem. Soc. 2005, 127, 6962ꢀ6963; (f) J.ꢀM. Tang,
S. Bhunia, S. M. A. Sohel, M.ꢀY. Lin, H.ꢀY. Liao, S. Datta, A. Das,
R.ꢀS. Liu, J. Am. Chem. Soc. 2007, 129, 15677ꢀ15683; (g) F.
Gagosz, Org. Lett., 2005, 7, 4129ꢀ4132; (h) C. NietoꢀOberhuber,
M.P. Munoz, E. Bunuel, C. Nevado, D. J. Cardenas, A. M.
Echavarren, Angew. Chem. Int. Ed. 2004, 43, 2402ꢀ2406; (i) E.
JimenezꢀNunez, K. Olawi, A. M. Echavarren, Chem. Commun.,
2009, 7327ꢀ7327; (j) N. Chatani, T. Morimoto, T. Muto, S. Murai,
J. Am. Chem. Soc., 1994, 116, 6049ꢀ6050.
(eq 2). In the presence of P(tꢀBu)2(oꢀbiphenyl)AuSbF6 (5 mol %),
this acyclic diene reacted slowly with benzaldehyde (2 equiv) in
dichloromethane to produce two diasteromeric cycloadducts 2h
and 2h’ in nearly equal proportion whereas 1,7ꢀenyne 1h gave
only oxacyclic product 2h (Table 2, entry 7). The proposed
structure of species 2h’ was inferred by the coupling constants of
60
65
70
5
the OCHPh proton (dd,
J = 4.4, 1.2 Hz). The poor
diastereoselectivity of species IIIh precludes its participation in
10 this enyne cycloaddition.
3.
E. J. Nunez, C. K. Claverie, C. NietoꢀOberhuber, A. M. Echavarren,
Angew. Chem. Int. Ed., 2006, 45, 5452ꢀ5455.
4. (a) K. Molawi, N. Delpont, A. M. Echavarren, Angew Chem. Int. Ed.,
2010, 49, 5317ꢀ3519; (b) L. Radtke, M.Willot, H. S. S. Ziegler, S.
Saurland, C. Srohmann, R. Frohlich, P.Habenberger, H. Waldmann,
M.Christmann, Angew Chem. Int. Ed., 2011, 50, 3998ꢀ4002.
As shown in Scheme 2, we postulate that cycloadduct 2a
likely arose from the interception of goldꢀcontaining
cyclobuteniumꢀlike intermediate B12 with benzaldehyde giving
chairꢀlike transition state C, ultimately giving observed product
15 2a stereoselectively. This reaction model also rationalizes our
observation on aldehyde substrates that electronꢀrich aryl
aldehydes are more efficient than their electronꢀdeficient
analogues (Table 3, entries 1ꢀ4) in the cycloaddition reactions as
the former shows great nucleophilicity to intercept species B.
5.
A. EscribanoꢀCuesta, V. LopezꢀCarrillo, D. Janssen, A. M.
Echavarren, Chem, Eur. J., 2009, 15, 5646ꢀ5650.
M. Schelwies, A.L. Dempwolff, F. Rominger, G. Helmchen, Angew
Chem. Int. Ed., 2007, 46, 5598ꢀ5601.
75 6.
7. Reviews for goldꢀcatalyzed cycloaddition reactions, see: (a) a) A. S.
K. Hashmi,. Chem. Rev. 2007, 107, 3180ꢀ3211; b) A. Fürstner,
Chem. Soc. Rev. 2009, 38, 3208ꢀ3221; c) N. T. Patil. Y. Yamamoto,
Chem. Rev. 2008, 108, 3395ꢀ3442; d) S. M. A. Sohel, R.ꢀS. Liu,
Chem. Soc. Rev. 2009, 38, 2269–2281; e) F. López, J. L.
Mascareñas, Beilstein, J. Org. Chem. 2011, 7, 1075ꢀ1094; f) C.
Aubert, L. Fensterbank, P. Garcia, M. Malacria, A. Simonneau,
Chem. Rev. 2011, 111, 1954.
20
80
85 8.
We just reported [2+2+3]ꢀcycloadditions of 1,6ꢀenynes with
nitrones, but these enynes gave only cycloisomerization
products when benzaldehyde was used. See S. A. Gawade, S.
Bhunia, R.ꢀS. Liu, Angew. Chem. Int. Ed. 2012, 51, 7835-38.
25
9. (a) A. Fürstner, A. Schlecker, C. W. Lehmann, Chem. Commun.,
2007, 4277ꢀ4279; (b) G. B. Bajracharya, I. Nakamura, Y.
Yamamoto, J. Org. Chem., 2005, 70, 892ꢀ897.
90
10.
Crystallogtaphic data of compound 2a is deposited at Cambridge
Crystallographic Data Center (CCDC 896604)
30
.
11.
Treatment of cyclobutene 3a with benzaldehyde (2 equiv) and P(tꢀ
Bu)2(oꢀbiphenyl)AuSbF6 in DCM (25 0C, 12 h) gave unreacted 3a in
76% recovery.
95
Scheme 2. Stereochemical course and reaction mechanism
12.
In Scheme 2, intermediate B is represented with two resonance
structures B’ and B”; this character will retard the conversion of this
intermediate to bicyclic cyclobutadiene 3a via an elimination of gold
35
In summary, we report a goldꢀcatalyzed stereoselective
cycloaddition of 1,7ꢀenynes13 with various carbonyl species. This
cycloaddition proceeds with a wide scope of enynes and carbonyl
species in reasonable proportions with an efficient suppression of
cycloisomerization byproduct. Based on our experimental data,
100
fragment.
40 we postulate that the formation of such [2+2+2]ꢀcycloadducts
arise from an efficient interception of cyclobuteniumꢀlike
intermediate B. This work highlights the utility of gold catalysis
in cycloaddition reactions.
105
13. The [2+2+2] formal cycloadditions failed to work with substrates
bearing 1,2ꢀdisubstituted alkenes including 2ꢀsubstituted 4ꢀmethoxyꢀ
phenyl group.
Notes and references
45 1.
(a) E. JiménezꢀNúñez, A. M. Echavarren, Chem. Rev. 2008, 108,
3326 3350; (b) D. J. Gorin, B. D. Sherry, F. D. Toste, Chem. Rev.
2008, 108, 3351ꢀ3378; (c) A. S. K. Hashmi, M. Rudolph, Chem.
Soc. Rev. 2008, 37, 1766ꢀ1775; (d) A. Fürstner, P. W. Davies,
Angew. Chem. Int. Ed. 2007, 46, 3410ꢀ3449; (e) L. Zhang, J. Sun,
S. A. Kozmin, Adv. Synth. Catal. 2006, 348, 2271ꢀ2296.
50
2.
For Au and Ptꢀcatalyzed cycloisomerizations of 1,nꢀenynes (n = 5ꢀ
7), see selected examples: (a) E. JiménezꢀNúñez, K. Molawi, A. M.
Echavarren, Chem. Commun. 2009, 7327ꢀ7329; (b) A. Fürstner, P.
Hannen, Chem. Eur. J. 2006, 12, 3006ꢀ3019; (c) X. Linghu, J. J.
KennedyꢀSmith, F. D. Toste, Angew. Chem. Int. Ed. 2007, 46,
55
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We report a gold-catalyzed [2+2+2]-cycloaddition of 1,7-enyne with carbonyl
species; the resulting oxacyclic cycloadducts arose from an interception of
gold-containing cyclobutenium intermediates with carbonyl species.