Synthesis of hydronaphthalenes through coupling of enyne-carbonyl compounds that contain pendant alkane groups with Fischer carbene complexes

Article abstract of DOI:10.1016/j.tetlet.2010.05.049

The coupling of enyne-carbonyl compounds that contain pendant alkene groups with Fischer carbine complexes to afford furans that contain pendant alkene groups is described. Subsequent intramolecular DielsAlder reactions are effective in selected cases, resulting in hydronaphthalene systems after dehydration. Although the DielsAlder event is thermodynamically unfavorable, the overall transformation of alkenefurans to dihydronaphthalenes is a favorable process.

Full text of DOI:10.1016/j.tetlet.2010.05.049

Tetrahedron Letters 51 (2010) 3682–3684
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis of hydronaphthalenes through coupling of enyne-carbonyl
compounds that contain pendant alkane groups with Fischer carbene
complexes
Rajesh Kumar Patti, Shaofeng Duan, Alejandro Camacho-Davila, Kris Waynant, Kenneth A. Dunn,
*
James W. Herndon
Department of Chemistry & Biochemistry, New Mexico State University, Las Cruces, NM 88003, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 16 March 2010
Revised 3 May 2010
Accepted 12 May 2010
Available online 20 May 2010
The coupling of enyne-carbonyl compounds that contain pendant alkene groups with Fischer carbene
complexes to afford furans that contain pendant alkene groups is described. Subsequent intramolecular
Diels–Alder reactions are effective in selected cases, resulting in hydronaphthalene systems after dehy-
dration. Although the Diels–Alder event is thermodynamically unfavorable, the overall transformation
of alkene–furans to dihydronaphthalenes is a favorable process.
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
Recently, a novel synthesis of hydrophenanthrenes (e.g., 5,
Scheme 1) involving the coupling of 2-alkynylbenzoyl systems
(e.g., 1) with
c,d-unsaturated Fischer carbene complexes (e.g., 2)
OMe
was reported.1 This reaction proceeds through a series of tandem
events that eventually lead to the formation of an isobenzofuran
ring system containing a pendant alkene group (3), which under-
goes intramolecular Diels–Alder reaction and oxanorbornene ring
opening to afford the observed product 5. In this Letter, attempts
to effect an analogous process using simple furans (e.g., 7a) gener-
ated from non-aromatic enyne-carbonyl compounds (e.g., 6a) is re-
ported.2 The net conversion represents construction of two new
ring systems in a single reaction event. This latter process is con-
siderably more challenging than generation of oxanorbornene 4
from isobenzofuran 3 since the Diels–Alder step involves furans
and not isobenzofurans. Examples of successful intramolecular
Diels–Alder reactions have been reported for simple furans,3 how-
ever, they appear to be less reliable relative to analogous reactions
involving isobenzofurans. Most of the high-yielding reactions
involve activated systems such as electron-deficient alkenes,4
Cr(CO)5
OMe
TMS
TMS
+
O
CHO
1
2
3
O
OMe
TMS
TMS
H
O
H
OH
5
4
THIS STUDY:
TMS
Cr(CO)5
OMe
allenes,5 and
a
favorable gem dialkyl effect.6 Six-membered
+
ring-forming intramolecular furan Diels–Alder reactions involving
unactivated alkenes are often low-yielding,7 although several high-
yielding processes have been reported.8 The net transformation is a
unique construction of a hydronaphthalene9 from two five-carbon
pieces where both components contribute at least one carbon to
both of the newly formed rings.
O
H
2
6a
OMe
H
OMe
TMS
TMS
?
O
O
8a
7a
Scheme 1.
* Corresponding author. Tel.: +1 505 646 2505; fax: +1 575 646 2649.
E-mail address: jherndon@nmsu.edu (J.W. Herndon).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.05.049

R. Kumar Patti et al. / Tetrahedron Letters 51 (2010) 3682–3684
3683
R
In the initial studies, the carbene–alkyne coupling reactions
were conducted in dioxane. As noted in Scheme 3, there is NO rea-
son for optimism concerning the Diels–Alder reactions of 7b–i. The
carbene coupling reaction provides the vinylfuran derivatives 7b–i,
which do not undergo Diels–Alder reactions in any of the systems
depicted. Extended heating at reflux results in a slow decomposi-
tion process. Heating at higher temperatures also results in decom-
position. Hydrolysis affords a more robust compound, furan–
ketones 13a–i that is also thermally inert with respect to the
Diels–Alder reaction.
Pd(PPh3)2Cl2 /
CuI / Et3N / THF
Br
O
PBr3 / DMF
CHCl3
()n CHO
()n
9
10
R
R
MgBr
1.
()n CHO
2. PCC
()n
O
The reaction depicted in Scheme 4 is the only evidence of pos-
sible successful execution of the original objective. In this reaction,
a low yield of a secondary cyclization product, hexahydrophe-
nanthrene 14a, was observed. Compound 14a hypothetically re-
sults from dehydration of Diels–Alder adduct 8a, which was not
observed under these conditions. Two of the examples in Scheme
3 bear remarkable similarity to this system, the five-membered
analog 7b and the hydrolysis product 13b, yet no Diels–Alder-de-
rived products were observed in these relatively similar systems.
Greater focus was thus placed on 7a since it is the only system
where there is any remote glimmer of success.
R = TMS
K2CO3 / MeOH
6
6f/g
H
n = 0,1
R = TMS or n-Bu
6c,d
()n CHO
Scheme 2.
2. Results and discussion
*
Computational evaluation (DFT-B3LYP, 6-31G ) of selected
Diels–Alder reactions reveal that all of these reactions will be dif-
ficult (see Scheme 5). Although most of the simple intramolecular
Diels–Alder events are exothermic, all are very slightly endergonic
when entropic considerations are taken into consideration. Even
though the cyclohexane-fused system 7a was the only system
where there is any hint of the Diels–Alder event, there is very little
energetic difference in the five- and six-membered ring systems
(7a,b). Hydrolysis of enol ether 7d to the ketone 13d results in a
less favorable intramolecular Diels–Alder reaction. Successful
Diels–Alder reaction in the five-membered ring alkene-tethered
system (conversion of 13g to 15g) is very highly unlikely. The tan-
dem Diels–Alder reaction and dehydration process (conversion of
7a to 14a and water) is however highly exothermic and exergonic.
The calculations suggest that successful cyclization might be
achieved if the Diels–Alder reaction is coupled with the dehydra-
tion step. Tandem Diels–Alder reaction followed by oxanorbornene
ring opening and/or aromatization is a feature in many examples of
the highly successful amidofuran-based intramolecular Diels–Al-
der reactions.11 A likely mechanism for the dehydration step is de-
picted in Scheme 6 and involves ionization of the C–O bond as a
key step. Optimization of this process would ideally involve a high
boiling and highly polar solvent, thus DMF was employed for the
Diels–Alder reaction. Complete conversion of the furan to the desi-
lylated hydrophenanthrene derivative 18a occurred upon heating
the compound to reflux in DMF. The ideal condition for this process
involves performing the carbene–alkyne coupling in dioxane at
85 °C followed by replacing the dioxane with DMF and heating to
Enyne-carbonyl compounds were readily prepared using the
synthetic routes depicted in Scheme 2. Haloformylation of either
cyclohexanone or cyclopentenone10 to afford the b-bromoenal
derivative 10 followed by Sonogashira coupling afforded the eny-
ne-aldehyde derivative 6. Subsequent desilylation and/or synthetic
manipulation of the aldehyde carbonyl group led to additional eny-
ne-carbonyl systems.
R1
Cr(CO)5
R2
R3
R5
OMe
+
O
R6
R4
6b-i
2 R5 = -CH2CH2CH=CH2, R6 = H
11 R5 = -CH2CH2CH=CH2, R6 = n-C3H7
12 R5,6 = H
100 ºC
Dioxane
O
OMe
R5
R6
R1
R1
R5
R2
R3
R2
HCl
R6
O
O
100 ºC in Dioxane
aq. MeOH
155 ºC in Toluene in R3
13b-i
R4
R4
7b-i
a sealed tube (7e)
100 ºC in Dioxane
138 ºC in Xylene
(13i)
No Reaction (decomposition)
No Reaction
6, 7, 13 (R1 = H in 13 if R1 = TMS in 7)
Cr(CO)5
TMS
a R1 = TMS, R2,3 = -(CH2)4-, R4 = H, R5 = -(CH2)2CH=CH2, R6 = H (6a + 2)
b R1 = TMS, R2,3 = -(CH2)3-, R4 = H, R5 = -(CH2)2CH=CH2, R6 = H (6b + 2)
c R1 = H, R2,3 = -(CH2)4-, R4 = H, R5 = -(CH2)2CH=CH2, R6 = H (6c + 2)
d R1 = H, R2,3 = -(CH2)3-, R4 = H, R5 = -(CH2)2CH=CH2, R6 = H (6d + 2)
e R1 = n-Bu, R2,3 = -(CH2)3-, R4 = H, R5 = -(CH2)2CH=CH2, R6 = H (6e + 2)
f R1 = TMS, R2,3 = -(CH2)3-, R4 = -(CH2)3CH=CH2, R5,6 = H (6f + 12)
g R1 = H, R2,3 = -(CH2)3-, R4 = -(CH2)3CH=CH2, R5,6 = H (6g + 12)
h R1 = TMS, R2,3 = -(CH2)4-, R4 = H, R5 = -(CH2)2CH=CH2,
OMe
85 ºC
+
O
Dioxane
10 h
H
2
6a
OMe
OMe
OMe
TMS
TMS
TMS
+
O
O
R6 = n-Pr (6a + 11)
8a
7a
14a
i R1 = H, R2,3 = -(CH2)4-, R4 = H, R5 = -(CH2)2CH=CH2, R6 = n-Pr (6c + 11)
< 5%
57%
Not Observed
Scheme 3.
Scheme 4.

3684
R. Kumar Patti et al. / Tetrahedron Letters 51 (2010) 3682–3684
OMe
145 °C for 10 h, which affords the hydrophenanthrene 18a in 60%
OMe
H
yield12 accompanied by a trace of the aromatized compound 19a.
Since the thermodynamics for Diels–Alder reaction of five-mem-
bered ring analog 7b are basically identical, this analog was sub-
jected to similar reaction conditions. This process resulted in the
five-membered ring-fused adduct 18b, also accompanied by a
trace of aromatized compound 19b.13
TMS
TMS
()n
7,8b, n = 0: ΔH = -4.58, ΔG = +0.85
7,8a, n = 1: ΔH = -4.35, ΔG = +0.57
O
O
()n
8a,b
7a,b
O
O
In summary, we have demonstrated that the net [5+5]-cycload-
dition of 2-alkynylbenzaldehydes and
c,d-unsaturated carbene
ΔH = -1.18, ΔG = +4.21
complexes can be extended to non-aromatic enyne-aldehyde sys-
tems. The simple Diels–Alder step of the tandem reaction was
unsuccessful, however, can be conducted if conditions favoring a
Diels–Alder dehydration sequence were employed, resulting in
the direct formation of dihydronaphthalene derivatives.
O
H
O
15d
13d
OMe
OMe
Acknowledgment
TMS
TMS
ΔH = -17.48, ΔG = -25.38
This work was supported by the SCORE program of NIH
(5SC1GM083693).
O
O
14a
7a
+ H2O
O
References and notes
1. For the most recent example, see: Menon, S.; Sinha-Mahapatra, D.; Herndon, J.
W. Tetrahedron 2007, 63, 8788–8793.
2. Herndon, J. W.; Wang, H. J. Org. Chem. 1998, 63, 4564–4565.
3. (a) Keay, B. A.; Hunt, I. R. Adv. Cycloadd. 1999, 6, 173–210; (b) Kappe, C. O.;
Murphree, S. S.; Padwa, A. Tetrahedron 1997, 53, 14179–14233; (c) Ciganek, E.
Org. React. 1984, 32, 1–374.
4. For representative examples: (a) Claeys, S.; Van Haver, D.; De Clercq, P. J.;
Milanesio, M.; Viterbo, D. Eur. J. Org. Chem. 2002, 1051–1062; (b) Dorr, H.;
Rawal, V. H. J. Am. Chem. Soc. 1999, 121, 10229–10230; (c) Woo, S.; Keay, B. A.
Synlett 1996, 135–137; (d) Woo, S.; Keay, B. A. Tetrahedron: Asymmetry 1994, 5,
1411–1414; (e) Padwa, A.; Lynch, S. M.; Mejía-Oneto, J. M.; Zhang, H. J. Org.
Chem. 2005, 70, 2206–2218.
ΔH = +1.11, ΔG = +6.84
O
O
H
13g
15g
Scheme 5.
5. For representative examples, see: (a) Jung, M. E.; Min, S. J. J. Am. Chem. Soc.
2005, 127, 10834–10835; (b) Wu, H. J.; Yen, C. H.; Chuang, C. T. J. Org. Chem.
1998, 63, 5064–5070.
6. (a) Jung, M. E.; Gervay, J. J. Am. Chem. Soc. 1991, 113, 224–232; (b) Fischer, K.;
Huenig, S. J. Org. Chem. 1987, 52, 564–569.
7. (a) Dadwal, M.; Kesharwani, M. K.; Danayak, V.; Ganguly, B.; Mobin, S. M.;
Muruganantham, R.; Namboothiri, I. N. N. Eur. J. Org. Chem. 2008, 6106–6118;
(b) Namboothiri, I. N. N.; Ganesh, M.; Mobin, S. M.; Cojocaru, M. J. Org. Chem.
2005, 70, 2235–2243.
8. For examples, see: (a) Klein, L. L. J. Org. Chem. 1985, 50, 1770–1773; (b) Padwa,
A.; Ginn, J. D.; Eidell, C. K.; Lynch, S. M. J. Org. Chem. 2002, 67, 3412–3424; (c)
Wang, Q.; Padwa, A. Org. Lett. 2004, 6, 2189–2192.
OMe
TMS
OMe
TMS
H+
H
O
H
OH
16
8a
OMe
OMe
TMS
TMS
9. For a review of naphthalene and hydronaphthalene syntheses, see: de Koning,
C. B.; Rousseau, R. R.; van Otterlo, W. A. L. Tetrahedron 2003, 59, 7–36.
10. Brahma, S.; Ray, J. K. Tetrahedron 2008, 64, 2883–2896.
11. (a) Padwa, A.; Dimitroff, M.; Waterson, A. G.; Wu, T. J. Org. Chem. 1998, 63,
3986–3997; (b) Padwa, A.; Ginn, J. D. J. Org. Chem. 2005, 70, 5197–5206.
12. Spectral data for 18a: 1H NMR (CDCl3): d 6.86 (d, 1H, J = 7.2 Hz), 6.75 (d, 1H,
J = 7.2 Hz), 5.63 (s, 1H), 3.72 (s, 3H) 2.83 (t, 2H, J = 7.5 Hz), 2.73 (t, 2H, J =
5.8 Hz), 2.68 (t, 2H, J = 5.8 Hz), 2.35 (t, 2H, J = 7.5 Hz), 1.90–1.70 (m, 4H); 13C
NMR: d 160.7 (C), 135.4 (C), 133.2 (C), 130.4 (C), 129.4 (C), 125.2 (CH), 124.3
(CH), 92.6 (CH), 54.7 (CH3), 30.1 (CH2), 29.0 (CH2), 27.4 (CH2), 26.3 (CH2), 23.5
14a
OH
17
+ H2O
Cr(CO)5
OMe
TMS
85 o
C
(CH2), 22.8 (CH2); IR (neat): 1660 (s) cmÀ1; HRMS (ESI): Calcd for C15H19
(MH)+ 215.1436, found 215.1431.
O
+
O
Dioxane
()n
13. Preparation of 18b: To a solution of enyne aldehyde 6b (0.200 g, 1.00 mmol) in
dioxane (20 mL) under nitrogen atmosphere at 85 °C added dropwise
H
a
2
6
solution of carbene 2 (0.392 g, 1.35 mmol) in dioxane (5 mL) over a 5-min
period. The mixture was stirred for 10 h at 85 °C and then cooled to room
temperature and filtered through Celite. The solvent was removed on a rotary
evaporator. The oil obtained was dissolved in dimethylformamide (15 mL) and
heated to 145 °C for 7 h and then cooled to room temperature. Hexane (20 mL)
was added and the mixture was washed two times with water. After removal
of the hexane on a rotary evaporator, final purification was achieved using
flash chromatography using 19:1 hexane/ethyl acetate as eluent. A colorless oil
identified as compound 18b (0.128 g, 64% yield) was obtained. 1H NMR
(CDCl3): d 6.90 (s, 2H), 5.53 (s, 1H), 3.74 (s, 3H), 2.93–2.83 (m, 6H), 2.41 (t, 2H,
J = 6.5 Hz), 2.09 (quintet, 2H, J = 7.0 Hz); 13C NMR (CDCl3): d 160.6, 142.3, 138.4,
131.0, 129.5, 125.0, 119.9, 93.5, 54.8, 32.9, 30.7, 28.5, 27.6, 25.1; HRMS (ESI):
Calcd for C14H17O (MH)+ 201.1274, found 201.1278.
OMe
OMe
OMe
TMS
()n
145 ºC
DMF
O
()n
()n
< 5%
18
19
7
yield 18
60%
64%
n
1 (a series)
0 (b series)
Scheme 6.