Use of acyl phosphonates as a coupling partner for rhodium-catalyzed [2+2+2] cycloaddition: Unexpected dependence of the reactivity on structures of α,ω-diynes

Article abstract of DOI:10.1055/s-2008-1077968

A cationic rhodium(I)-H₈-BINAP complex catalyzes a [2+2+2] cycloaddition of 1,6- and 1,7-diynes with acyl phosphonates in high yields with high regioselectivity. Interestingly, the reactivity of α,ω-diynes toward acyl phosphonates is highly dependent on their own structures.

Full text of DOI:10.1055/s-2008-1077968

LETTER
2017
Use of Acyl Phosphonates as a Coupling Partner for Rhodium-Catalyzed
[2+2+2] Cycloaddition: Unexpected Dependence of the Reactivity on
Structures of a,w-Diynes
A
cyl Phosphonates
e
as
a
Coup
n
ling
P
artner for Rho
T
dium-Catalyz
e
a
d
[2+2+2]
C
n
ycloadditio
a
n
ka,* Rie Tanaka, Goushi Nishida, Masao Hirano
Department of Applied Chemistry, Graduate School of Engineering, Tokyo University of Agriculture and Technology, Koganei, Tokyo
184-8588, Japan
Fax +81(42)3887037; E-mail: tanaka-k@cc.tuat.ac.jp
Received 2 May 2008
OH
Abstract: A cationic rhodium(I)–H8-BINAP complex catalyzes a
R2
[2+2+2] cycloaddition of 1,6- and 1,7-diynes with acyl phospho-
nates in high yields with high regioselectivity. Interestingly, the re-
activity of a,w-diynes toward acyl phosphonates is highly
dependent on their own structures.
P(O)(OEt)2
R1
alkylation
O
O
cycloaddition
P(O)(OEt)2
R1
Key words: acylphosphonates, alkynes, cycloaddition, H8-BINAP,
rhodium
R1
R2
R1
P(O)(OEt)2
olefination
P(O)(OEt)2
Catalytic [2+2+2] cycloadditions1 of diynes with C(sp2)-
heteroatom multiple bonds such as aldehydes and ketones
by using various transition-metal complexes as catalysts
have been reported.2–6 Recently, several groups have uti-
lized rhodium-based catalysts for this transformation. Oji-
ma and co-workers reported an intramolecular [2+2+2]
cycloaddition of diynal in their study of a [2+2+2+1] cy-
cloaddition with CO using [Rh(cod)Cl]2 as a catalyst.7
Kong and Krische reported a cationic rhodium(I)–
Scheme 1
We first investigated the reaction of tosylamide-linked
1,6-diyne 1a with acetyl phosphonate 2a in the presence
of a cationic rhodium(I)–bisphosphine complex as a cata-
lyst (Table 1). We were pleased to find that the reaction
proceeded at room temperature to give the desired di-
enone 3aa in moderate yield using 10 mol% of a
[Rh(cod)2]BF4–BINAP complex (entry 1). Among the bi-
arylbisphosphine ligands examined, the highest yield of
3aa was obtained when H8-BINAP was used as a ligand
(entry 3). Non-biarylbisphosphine ligand dppb, which
possesses a large bite angle, could be used, but the yield
was very low (entry 4). After optimization of the reaction
conditions, we determined that the reaction was complet-
ed within one hour and the use of two equivalents of 2a
further improved the yield of 3aa (entry 5).
BIPHEP
[2,2¢-bis(diphenylphosphino)-1,1¢-biphenyl]-
catalyzed carbonyl Z-dienylation via multicomponent re-
ductive coupling of aldehydes and a-keto esters mediated
by hydrogen in the presence of a catalytic amount of tri-
phenylacetic acid, which involves carbonyl insertion into
cationic rhodacyclopentadienes.8,9 We have reported cat-
ionic rhodium(I)–H8-BINAP-catalyzed [2+2+2] cycload-
ditions of 1,6-diynes with both activated and unactivated
carbonyl compounds with alkynes.10,11 On the other hand,
we have recently determined that alkynylphosphonates
are suitable substrates for cationic rhodium(I)–H8-
BINAP-catalyzed [2+2+2] cycloadditions.12 Accordingly,
we anticipated that acyl phosphonates, which are useful
building blocks for the synthesis of functionalized phos-
phorus compounds via alkylation13 or olefination,14 would
show high reactivity in cationic rhodium(I)–H8-BINAP-
catalyzed [2+2+2] cycloaddition (Scheme 1).15,16 In this
communication, we describe a cationic rhodium(I)–H8-
BINAP-catalyzed [2+2+2] cycloaddition of acyl phos-
phonates with 1,6-diynes leading to phosphonate-substi-
tuted dienones.
Thus, we explored the scope of this process with respect
to both acyl phosphonates and a,w-diynes (Table 2). Not
only acetyl phosphonate (2a, entry 1) but also benzoyl
phosphonate (2b, entry 2) could participate in this reac-
tion. With respect to 1,6-diynes, not only symmetrical 1,6-
diynes 1a but also unsymmetrical 1,6-diynes 1b and 1c re-
acted with acyl phosphonates to give the corresponding
dienones in good yields with perfect regioselectivity (en-
tries 3 and 4). Interestingly, the reactivity of a,w-diynes is
highly dependent on their own structures. Terminal 1,6-
diyne 1d failed to react with 2b due to the rapid homocy-
clotrimerization of 1d (entry 5).17 Tosylamide-linked in-
ternal 1,6-diyne 1a smoothly reacted with 2b (entry 2),
while malonate- and dimethoxypropane-linked internal
1,6-diynes 1e and 1f failed to react with 2b, and they re-
mained unchanged (entries 6 and 7). In the case of 1,7-
diynes, although internal 1,7-diyne 1g failed to react with
2b (entry 8), the reaction of terminal 1,7-diyne 1h with
SYNLETT 2008, No. 13, pp 2017–2022
x
x
.x
x
.2
0
0
8
Advanced online publication: 15.07.2008
DOI: 10.1055/s-2008-1077968; Art ID: U04708ST
© Georg Thieme Verlag Stuttgart · New York

2018
K. Tanaka et al.
LETTER
Table 1 Screening of Ligands for Rh-Catalyzed [2+2+2] Cycloaddition of 1,6-Diyne 1a with Acetyl Phosphonate 2aa
Me
[Rh(cod)2]BF4/ligand
Me
Me
O
(10 mol%)
O
Z
+
Z
Me
CH2Cl2, r.t.
Me
P(O)(OEt)2
1a (Z = NTs)
2a
Me
P(O)(OEt)2
3aa
O
O
O
PPh2
PPh2
PPh2
PPh2
PPh2
PPh2
PPh2
PPh2
dppb
O
H8-BINAP
Segphos
Ligand
BINAP
Segphos
BINAP
Entry
2a (equiv)
1.1
Time (h)
Yield (%)b
1
2
3
4
5
16
16
16
16
1
55
67
73
13
84
1.1
H8-BINAP
dppb
1.1
1.1
H8-BINAP
2.0
a [Rh(cod)2]BF4 (0.010 mmol), ligand (0.010 mmol), 1a (0.10 mmol), 2a (0.11 or 0.20 mmol), and CH2Cl2 (1.5 mL) were used.
b Isolated yield.
Table 2 Rh(I)+–H8-BINAP-Catalyzed [2+2+2] Cycloaddition of 1,6- and 1,7-Diynes 1 with Acyl Phosphonates 2a
R1
R1
[Rh(cod)2]BF4/H8-BINAP
(10 mol%)
O
Z
+
O
R3
P(O)(OEt)2
Z
R2
R2
CH2Cl2, r.t.
1 h
1
2
(2 equiv)
R3
P(O)(OEt)2
3
Entry
1 (Z, R1, R2)
2 (R3)
3
Yield (%, E/Z)b
84 (88:12)c
90 (40:60)
71 (59:41)c
78 (40:60)
0 (–)d
1
2
1a (NTs, Me, Me)
1a (NTs, Me, Me)
2a (Me)
2b (Ph)
2b (Ph)
2a (Me)
2b (Ph)
2b (Ph)
2b (Ph)
2b (Ph)
2a (Me)
2b (Ph)
3aa
3ab
3bb
3ca
3db
3eb
3fb
3gb
3ha
3hb
3
1b (NTs, Me, CO2Me)
1c (NTs, Me, H)
4
5
1d (NTs, H, H)
6
1e [C(CO2Me)2, Me, Me]
1f [C(CH2OMe)2, Me, Me]
1g (CH2CH2, Me, Me)
1h (CH2CH2, H, H)
1h (CH2CH2, H, H)
0 (–)e
7
0 (–)e
8
0 (–)e
9
70 (60:40)
76 (63:37)
10
a [Rh(cod)2]BF4 (0.020 mmol), H8-BINAP (0.020 mmol), 1a–h (0.20 mmol), 2a,b (0.40 mmol), and CH2Cl2 (1.5 mL) were used.
b Isolated yield.
c Isolated as a mixture of E/Z isomers.
d Homo-[2+2+2] cycloaddition of 1d proceeded.
e Diynes 1 remained almost unchanged.
Synlett 2008, No. 13, 2017–2022 © Thieme Stuttgart · New York

LETTER
Acyl Phosphonates as a Coupling Partner for Rhodium-Catalyzed [2+2+2] Cycloaddition
2019
Me
O
O
Ph
Ph
P(O)(OEt)2
[Rh(cod)2]BF4/H8-BINAP
(10 mol%)
TsN
Me
Me
MeO2C
MeO2C
Me
2b (1.1 equiv)
+
O
CH2Cl2, r.t.
1 h
3ab
Ph
P(O)(OEt)2
1e
CO2Et
2c (1.1 equiv)
Me
Me
Me
Me
O
OEt
P
2b
MeO2C
MeO2C
MeO2C
+
O
O
TsN
EtO
P(O)(OEt)2
Ph
Rh(I)+
Ph
Me
Me
MeO2C
O
O
P
P
Rh+
O
Ph
P(O)(OEt)2
Ph
CO2Et
O
OEt
OEt
P
3eb 37% (E/Z = 54:46)
3ec 62% (E/Z = 29:71)
Ph
A
Scheme 2
P
P
Rh+
Me
1a
2b
OEt
O
P(O)(OEt)2
Ph
acyl phosphonates proceeded in good yields (entries 9 and
10).17
EtO
D
TsN
P
Me
Ph
As we already demonstrated that keto esters are highly re-
active coupling partners for cationic rhodium(I)–H8-
BINAP-catalyzed [2+2+2] cycloaddition with 1,6-diynes,
a chemoselective [2+2+2] cycloaddition of 1e with acyl
O
O
P(OEt)2
Ph
O
P
Me
Rh+
P
P
O
Rh+
N
O
S
P
O
Tol
Me
N
B
O
Tol
S
Table 3 Rh(I)+–H8-BINAP-Catalyzed [2+2+2] Cycloaddition of
1,6-and 1,7-Diynes 1e–g with Benzoyl Phosphonate (2b) in the Pres-
ence of Ethyl Phenylglyoxylate (2c)a
C
O
Me
Me
Scheme 3
O
Ph
Ph
P(O)(OEt)2
[Rh(cod)2]BF4/H8-BINAP
(10 mol%)
phosphonate 2b and keto ester 2c was investigated in the
presence of the cationic rhodium(I)–H8-BINAP catalyst
(Scheme 2). We anticipated that 1e selectively reacts with
2c leading to ester-substituted dienone 3ec. Contrary to
our expectation, 1e reacted with both 2b and 2c.
Me
Me
2b (1.1 equiv)
Z
O
CH2Cl2, r.t., 1 h
Me
Me
CO2Et
1e–g
2c
O
O
Z
Z
As the presence of keto ester 2c plays an important role in
the present catalysis, the amount of 2c was examined as
shown in Table 3. Increasing the amount of 2c decreased
the yield of 3eb and increased the yield of 3ec (entries 1–
4). However, dimethoxypropane-linked 1,6-diyne 1f and
ethylene-linked 1,7-diyne 1g failed to react with 2b even
in the presence of 2c (entries 5 and 6).
Me
Me
Ph
P(O)(OEt)2
Ph
CO2Et
3eb–gb
3ec–gc
Entry 1 (Z)
2c
(equiv)
3eb–gb
3ec–gc
Yield
Yield
(%, E/Z)b
(%, E/Z)b
Scheme 3 depicts a possible mechanism for the rhodium-
catalyzed [2+2+2] cycloaddition of tosylamide-linked
1,6-diyne 1a with benzoyl phosphonate 2b. The reaction
of 1a and 2b with rhodium generates an equilibrium mix-
ture of intermediates A and B through the bidentate coor-
dination of both 1a and 2b.18 Intermediate B subsequently
undergoes oxidative coupling leading to intermediate C.
Insertion of another alkyne moiety of 1a furnishes inter-
mediate D. Reductive elimination of rhodium followed by
electrocyclic ring opening furnishes dienone 3ab. Indeed,
a homo-[2+2+2] cycloaddition product of 1a through a
rhodacyclopentadiene intermediate was not observed in
the reaction of 1a and 2b.
1
2
3
4
5
1e [Z = C(CO2Me)2] 0
1e [Z = C(CO2Me)2] 0.2
1e [Z = C(CO2Me)2] 1.1
1e [Z = C(CO2Me)2] 2.0
0c
–
74 (52:48)
37 (52:48)
5 (45:55)
0c
19 (29:71)d
62 (29:71)d
76 (29:71)d
0c
1f
1.1
[Z = C(CH2OMe)2]
6
1g (Z = CH2CH2)
1.1
0c
0c
a [Rh(cod)2]BF4 (0.020 mmol), H8-BINAP (0.020 mmol), 1e–g (0.20
mmol), 2b (0.22 mmol), 2c (0–0.40 mmol), and CH2Cl2 (1.5 mL)
were used.
b Isolated yield.
On the other hand, the equilibration of intermediates A
and E–H may account for the results shown in Table 3
(Scheme 4).
c Diynes 1 remained almost unchanged.
d Isolated as a mixture of E/Z isomers.
Synlett 2008, No. 13, 2017–2022 © Thieme Stuttgart · New York

2020
K. Tanaka et al.
LETTER
References and Notes
OEt
OEt
P
EtO
O
EtO
EtO
P
(1) For recent reviews of transition-metal-catalyzed [2+2+2]
cycloadditions, see: (a) Agenet, N.; Buisine, O.; Slowinski,
F.; Gandon, V.; Aubert, C.; Malacria, M. In Organic
Reactions, Vol. 68; Overman, L. E., Ed.; John Wiley:
Hoboken, 2007, 1. (b) Heller, B.; Hapke, M. Chem. Soc.
Rev. 2007, 36, 1085. (c) Chopade, P. R.; Louie, J. Adv.
Synth. Catal. 2006, 348, 2307. (d) Gandon, V.; Aubert, C.;
Malacria, M. Chem. Commun. 2006, 2209. (e) Kotha, S.;
Brahmachary, E.; Lahiri, K. Eur. J. Org. Chem. 2005, 4741.
(f) Yamamoto, Y. Curr. Org. Chem. 2005, 9, 503.
(g) Robinson, J. E. In Modern Rhodium-Catalyzed Organic
Reactions; Evans, P. A., Ed.; Wiley-VCH: Weinheim, 2005,
129. (h) Varela, J. A.; Saá, C. Chem. Rev. 2003, 103, 3787.
(2) For the use of stoichiometric cobalt reagents, see:
(a) Harvey, D. F.; Johnson, B. M.; Ung, C. S.; Vollhardt, K.
P. C. Synlett 1989, 15. (b) For the use of stoichiometric
zirconacyclopentadienes, see: Gleiter, R.; Schehlmann, V.
Tetrahedron Lett. 1989, 30, 2893. (c) Takahashi, T.; Li, Y.;
Ito, T.; Xu, F.; Nakajima, K.; Liu, Y. J. Am. Chem. Soc.
2002, 124, 1144.
Ph
Ph
Ph
2c
O
O
O
O
2c
2b
O
P
P
P
P
P
P
Rh+
O
Rh+
Rh+
O
O
O
O
OEt
OEt
2b
O
P
OEt
OEt
Ph
Ph
Ph
F
A
E
1e
2c
1e
EtO
2c
OEt
P
EtO
Ph
Me
Ph
Me
O
O
O
O
P
P
P
P
Rh+
Rh+
O
O
MeO
MeO
MeO2C
MeO2C
H
G
Me
Me
(3) For Ni catalysis, see: (a) Tsuda, T.; Kiyoi, T.; Miyane, T.;
Saegusa, T. J. Am. Chem. Soc. 1988, 110, 8570.
(b) Tekavec, T. N.; Louie, J. Org. Lett. 2005, 7, 4037.
(c) Tekavec, T. N.; Louie, J. J. Org. Chem. 2008, 73, 2641.
(4) For Ni-catalyzed [4+2+2] cycloaddition of 1,6-diynes with
cyclobutanones, see: Murakami, M.; Ashida, S.; Matsuda, T.
J. Am. Chem. Soc. 2006, 128, 2166.
3ec
3eb
Scheme 4
In the absence of keto ester 2c, two molecules of benzoyl
phosphonate 2b coordinate to rhodium in a bidentate fash-
ion to generate intermediate A due to higher coordination
ability of 2b than that of malonate-linked 1,6-diyne 1e,
which results in no conversion of 1e. In the presence of 2c,
an equilibrium mixture of intermediates A, E, and F may
be generated. Subsequent ligand exchange between 1e
and weakly coordinated 2c may generate intermediates G
and H, which furnish dienones 3eb and 3ec, respectively,
depending on the amount of 2c.18 Dimethoxypropane-
linked 1,6-diyne 1f fails to react with both intermediates
E and F presumably due to lower coordination ability of
ether oxygen than that of ester carbonyl oxygen. Obvious-
ly, ligand exchange between ethylene-linked 1,7-diyne 1g
bearing no heteroatom in the linker and 2c would be diffi-
cult to proceed.17
(5) For Ru catalysis, see: Yamamoto, Y.; Takagishi, H.; Itoh, K.
J. Am. Chem. Soc. 2002, 124, 6844.
(6) For Ru(II)-catalyzed hydrative cyclization and [4+2]
cycloaddition of yne-enones, see: Trost, B. M.; Brown, R.
E.; Toste, F. D. J. Am. Chem. Soc. 2000, 122, 5877.
(7) Bennacer, B.; Fujiwara, M.; Lee, S.-Y.; Ojima, I. J. Am.
Chem. Soc. 2005, 127, 17756.
(8) Kong, J. R.; Krische, M. J. J. Am. Chem. Soc. 2006, 128,
16040.
(9) For examples of carbonyl insertion into a Rh–C bond, see:
(a) Krug, C.; Hartwig, J. F. J. Am. Chem. Soc. 2002, 124,
1674. (b) Fujii, T.; Koike, T.; Mori, A.; Osakada, K. Synlett
2002, 298.
(10) (a) Tanaka, K.; Otake, Y.; Wada, A.; Noguchi, K.; Hirano,
M. Org. Lett. 2007, 9, 2203. After our publication, a similar
manuscript was published, see: (b) Tsuchikama, K.;
Yoshinami, Y.; Shibata, T. Synlett 2007, 1395.
(11) Recently, we have reported a cationic rhodium(I)–H8-
BINAP-catalyzed regio-, diastereo-, and enantioselective
[2+2+2] cycloaddition of 1,6-enynes with electron-deficient
ketones. See: Tanaka, K.; Otake, Y.; Sagae, H.; Noguchi, K.;
Hirano, M. Angew. Chem. Int. Ed. 2008, 47, 1312.
(12) (a) Nishida, G.; Noguchi, K.; Hirano, M.; Tanaka, K. Angew.
Chem. Int. Ed. 2007, 46, 3951. (b) Nishida, G.; Noguchi,
K.; Hirano, M.; Tanaka, K. Angew. Chem. Int. Ed. 2008, 47,
3410.
In conclusion, we have determined that a cationic rhodi-
um(I)–H8-BINAP complex catalyzes a [2+2+2] cycload-
dition of 1,6- and 1,7-diynes with acyl phosphonates in
high yields with high regioselectivity. Interestingly, the
reactivity of a,w-diynes toward acyl phosphonates is
highly dependent on their own structures.19
(13) For selected recent examples, see: (a) Mandal, T.; Samanta,
S.; Zhao, C.-G. Org. Lett. 2007, 9, 943. (b) Samanta, S.;
Zhao, C.-G. J. Am. Chem. Soc. 2006, 128, 7442. (c) Demir,
A. S.; Reis, O.; Kayalar, M.; Eymur, S.; Reis, B. Synlett
2006, 3329. (d) Kim, D. Y.; Wiemer, D. F. Tetrahedron
Lett. 2003, 44, 2803.
(14) For examples, see: (a) Yamashita, M.; Kojima, M.; Yoshida,
H.; Ogata, T.; Inokawa, S. Bull. Chem. Soc. Jpn. 1980, 53,
1625. (b) Kojima, M.; Yamashita, M.; Yoshida, H.; Ogata,
T. Synthesis 1979, 147.
Acknowledgment
This work was supported partly by a Grant-in-Aid for Scientific Re-
search [No. 19350046, No. 19·8995, No. 20675002, and No.
19028015 (Chemistry of Concerto Catalysis)] from the Ministry of
Education, Culture, Sports, Science and Technology, Japan. We
thank Takasago International Corporation for the gift of modified-
BINAP ligands.
(15) To the best of our knowledge, only two examples of a
cycloaddition reaction using acyl phosphonates as a
Synlett 2008, No. 13, 2017–2022 © Thieme Stuttgart · New York

LETTER
Acyl Phosphonates as a Coupling Partner for Rhodium-Catalyzed [2+2+2] Cycloaddition
2021
coupling partner have been reported. For a photochemical
cycloaddition with aziridines, see: (a) Gakis, N.;
16.2, 16.1. 31P NMR (121 MHz, CDCl3): d = 14.5.
Compound (Z)-3ab: pale yellow oil. 1H NMR (300 MHz,
CDCl3): d = 7.76 (d, J = 8.4 Hz, 2 H), 7.41–7.24 (m, 5 H),
7.17–7.09 (m, 2 H), 4.52 (s, 2 H), 4.51–4.28 (m, 2 H), 3.92–
3.67 (m, 2 H), 3.78–3.52 (m, 2 H), 2.40 (s, 3 H), 2.32 (s, 3
Heimgartner, H.; Schmid, H. Helv. Chim. Acta 1975, 58,
748. For hetero-Diels–Alder reactions involving a,b-
unsaturated acyl phosphonates, see: (b) Evans, D. A.;
Johnson, J. S.; Olhava, E. J. J. Am. Chem. Soc. 2000, 122,
1635.
H), 1.68 (d, J = 2.7 Hz, 3 H), 1.04 (t, J = 7.2 Hz, 6 H). 13
NMR (75 MHz, CDCl3): d = 193.9, 148.7, 148.6, 145.3,
C
(16) For our accounts of [2+2+2] cycloadditions catalyzed by a
cationic rhodium(I)–BINAP-type bisphosphine complex,
see: (a) Tanaka, K. Synlett 2007, 1977. (b) Tanaka, K.;
Nishida, G.; Suda, T. J. Synth. Org. Chem. Jpn. 2007, 65,
862.
145.2, 143.7, 136.0, 135.9, 134.0, 133.5, 132.04, 132.03,
131.1, 129.8, 128.83, 128.77, 128.53, 128.51, 127.83,
127.80, 127.5, 62.14, 62.06, 59.0, 55.3, 28.7, 21.5, 21.4,
21.2, 16.1, 16.0. 31P NMR (121 MHz, CDCl3): d = 14.0.
Compound 3bb: pale yellow oil. 1H NMR (300 MHz,
CDCl3): d (E-isomer) = 7.73 (d, J = 7.8 Hz, 2 H), 7.41–7.05
(m, 7 H), 4.60 (t, J = 4.2 Hz, 2 H), 4.37 (t, J = 4.2 Hz, 2 H),
3.91–3.77 (m, 2 H), 3.77–3.60 (m, 2 H), 3.36 (d, J = 0.9 Hz,
3H), 2.43 (s, 3 H), 2.38 (s, 3 H), 1.05 (t, J = 7.2 Hz, 6 H); d
(Z-isomer) = 7.57 (d, J = 7.5 Hz, 2 H), 7.41–7.05 (m, 5 H),
6.99 (d, J = 7.2 Hz, 2 H), 4.23 (t, J = 4.2 Hz, 2 H), 4.13–3.91
(m, 6 H), 3.82 (s, 3 H), 2.43 (s, 3 H), 2.22 (s, 3 H), 1.19 (t,
J = 7.2 Hz, 6 H). 13C NMR (75 MHz, CDCl3): d = 194.1,
193.7, 165.3, 164.8, 164.5, 143.7, 143.6, 141.0, 140.6,
140.5, 140.4, 140.3 138.7, 138.6, 138.5, 138.41, 138.38,
136.2, 136.0, 134.9, 134.8, 133.8, 133.7, 133.0, 129.8,
129.7, 128.6, 128.52, 128.49, 128.45, 128.22, 128.17, 127.9,
127.8, 127.6, 127.5, 127.4, 63.0, 62.9, 62.8, 59.88, 59.86,
59.3, 55.5, 55.3, 53.1, 52.5, 29.0, 28.8, 21.42, 21.38, 16.1,
16.0, 15.9. 31P NMR (121 MHz, CDCl3): d (E-isomer) =
11.9; d (Z-isomer) = 11.0.
(17) In general, terminal alkynes are more reactive and
coordinative toward rhodium than internal alkynes.
Therefore, the reaction of terminal 1,6-diyne 1d with 2b
results in the rapid homo-[2+2+2] cycloaddition of 1d via a
rhodacyclopentadiene intermediate. On the other hand, the
formation of the rhodacyclopentadiene intermediate from
terminal 1,7-diyne 1h may be slower than that from terminal
1,6-diynes for steric reasons. Thus, the reaction of 1h with
2b may furnish the oxarhodacyclopentene intermediate.
Insertion of another terminal alkyne moiety of 1h followed
by reductive elimination of rhodium furnishes the
corresponding cross-[2+2+2] cycloaddition product 3hb in
good yield.
(18) Equilibrium coordination of the ester carbonyl oxygen vs.
the alkyne moiety of a malonate-linked 1,6-diyne is
proposed in the Ru-catalyzed [2+2+2] cycloaddition of
alkynes, see: Yamamoto, Y.; Arakawa, T.; Ogawa, R.; Itoh,
K. J. Am. Chem. Soc. 2003, 125, 12143.
Compound (E)-3ca: pale yellow oil. 1H NMR (300 MHz,
CDCl3): d = 7.73 (d, J = 8.1 Hz, 2 H), 7.35 (d, J = 8.1 Hz, 2
H), 7.29–7.16 (m, 1 H), 4.46–4.35 (m, 4 H), 4.18–4.03 (m, 4
H), 2.44 (s, 3 H), 2.21 (s, 3 H), 1.85 (dd, J = 15.0, 1.5 Hz, 3
H), 1.33 (t, J = 7.2 Hz, 6 H). 13C NMR (75 MHz, CDCl3): d
= 194.0, 144.2, 141.7, 141.3, 135.5, 134.8, 133.2, 133.1,
132.9, 132.5, 130.0, 127.5, 62.3, 62.2, 57.8, 55.0, 29.9, 21.5,
16.4, 16.3, 14.9, 14.8. 31P NMR (121 MHz, CDCl3): d =
19.3.
(19) Typical Procedure (Table 2, entry 1)
Under an argon atmosphere, H8-BINAP (12.6 mg, 0.02
mmol) and [Rh(cod)2]BF4 (8.1 mg, 0.02 mmol) were
dissolved in CH2Cl2 (2.0 mL), and the mixture was stirred at
r.t. for 5 min. Hydrogen was introduced to the resulting
solution in a Schlenk tube. After stirring at r.t. for 1 h, the
resulting solution was concentrated to dryness and dissolved
in CH2Cl2 (0.5 mL). To this solution was added dropwise
over 1 min a solution of diyne 1a (55.1 mg, 0.20 mmol) and
acyl phosphonate 2a (72.1 mg, 0.40 mmol) in CH2Cl2 (1.0
mL) at r.t. The mixture was stirred at r.t. for 1 h. The
resulting solution was concentrated and purified by a
preparative TLC (hexane–EtOAc, 1:1), which furnished 3aa
(76.2 mg, 0.017 mmol, 84% yield) as a pale yellow oil.
Compound 3aa: IR (neat): 3052, 2983, 2867, 1661, 1347,
1237, 1164, 1022, 671 cm–1. 1H NMR (300 MHz, CDCl3): d
(E-isomer) = 7.74–7.63 (m, 2 H), 7.33–7.21 (m, 2 H), 4.49–
4.19 (m, 4 H), 3.97–3.73 (m, 4 H), 2.37 (s, 3 H), 2.10 (s, 3
H), 1.90–1.77 (m, 6 H), 1.16 (t, J = 7.2 Hz, 6 H); d (Z-
isomer) = 7.74–7.63 (m, 2 H), 7.33–7.21 (m, 2 H), 4.30–4.19
(m, 4 H), 4.12–3.97 (m, 4 H), 2.38 (s, 3 H), 2.10 (s, 3 H),
1.90–1.77 (m, 3 H), 1.58 (dd, J = 13.5, 1.5 Hz, 3 H), 1.28 (t,
J = 7.2 Hz, 6 H). 13C NMR (75 MHz, CDCl3): d = 193.9,
149.6, 149.4, 143.6, 142.8, 142.7, 133.9, 131.6, 129.9,
129.7, 127.4, 126.4, 124.0, 61.64, 61.56, 58.87, 58.86, 55.2,
28.3, 27.9, 21.4, 20.0, 19.8, 16.2, 16.11, 16.10, 15.9, 15.8.
31P NMR (121 MHz, CDCl3): d (E-isomer) = 17.8; d (Z-
isomer) = 17.9. ESI-HRMS: m/z calcd for C21H30NO6PSNa
[M + Na]+: 478.1429; found: 478.1428.
Compound (Z)-3ca: pale yellow oil. 1H NMR (300 MHz,
CDCl3): d = 7.74 (d, J = 8.1 Hz, 2 H), 7.33 (d, J = 8.1 Hz, 2
H), 6.77–6.54 (m, 1 H), 4.51–4.43 (m, 2 H), 4.37–4.29 (m, 2
H), 4.07–3.90 (m, 4 H), 2.42 (s, 3 H), 2.20 (s, 3 H), 2.04 (dd,
J = 13.2, 1.8 Hz, 3 H), 1.24 (t, J = 7.2 Hz, 6 H). 13C NMR (75
MHz, CDCl3): d = 194.1, 143.9, 143.8, 143.7, 134.2, 134.0,
133.9, 133.6, 133.48, 133.47, 131.9, 129.8, 127.6, 62.1,
62.0, 59.1, 59.0, 55.0, 29.8, 22.1, 22.0, 21.5, 16.3, 16.2. 31
NMR (121 MHz, CDCl3): d = 16.7.
P
Compound (E)-3eb: pale yellow oil. 1H NMR (300 MHz,
CDCl3): d = 7.25–7.15 (m, 3 H), 7.07–6.97 (m, 2 H), 4.12–
3.91 (m, 4 H), 3.60 (s, 6 H), 3.10–3.02 (m, 2 H), 2.95 (s, 2
H), 2.35 (d, J = 3.3 Hz, 3 H), 2.18 (s, 3 H), 1.20 (t, J = 7.2
Hz, 6 H). 13C NMR (75 MHz, CDCl3): d = 195.4, 171.0,
152.0, 151.7, 151.6, 151.4, 137.4, 137.3, 133.8, 129.8,
128.8, 128.7, 127.8, 127.5, 127.3, 61.9, 61.8, 56.8, 53.0,
44.9, 40.8, 29.0, 20.2, 20.1, 16.2, 16.1. 31P NMR (121 MHz,
CDCl3): d = 15.6.
Compound (Z)-3eb: pale yellow oil. 1H NMR (300 MHz,
CDCl3): d = 7.40–7.28 (m, 3 H), 7.22–7.16 (m, 2 H), 3.96–
3.70 (m, 4 H), 3.74 (s, 6 H), 3.70–3.30 (m, 4 H), 2.33 (s, 3
H), 1.79 (d, J = 2.4 Hz, 3 H), 1.10 (t, J = 7.2 Hz, 6 H). 13
NMR (75 MHz, CDCl3): d = 195.8 152.4, 152.2, 150.1,
C
Compound (E)-3ab: pale yellow oil. 1H NMR (300 MHz,
CDCl3): d = 7.51 (d, J = 8.4 Hz, 2 H), 7.28 (d, J = 8.4 Hz, 2
H), 7.16–7.00 (m, 3 H), 6.95–6.83 (m, 2 H), 4.12–3.87 (m, 8
H), 2.45 (s, 3 H), 2.29 (d, J = 3.3 Hz, 3 H), 2.17 (s, 3 H), 1.18
(t, J = 7.2 Hz, 6 H). 13C NMR (75 MHz, CDCl3): d = 193.3,
159.8, 148.7, 148.4, 147.6, 147.4, 143.7, 136.9, 133.1,
132.4, 131.8, 129.9, 128.22, 128.16, 127.91, 127.89, 127.62,
127.58, 127.3, 62.1, 62.0, 57.9, 54.8, 28.8, 21.5, 20.3, 20.2,
150.0, 136.8, 136.6, 133.9, 130.5, 129.11, 129.05, 128.4,
128.0, 127.5, 127.4, 61.9, 61.8, 57.3, 53.0, 45.6, 41.0, 28.9,
21.1, 20.9, 16.1, 16.0. 31P NMR (121 MHz, CDCl3): d =
14.7.
Compound (E)-3ha: pale yellow oil. 1H NMR (300 MHz,
CDCl3): d = 9.66 (s, 1 H), 7.14–7.00 (m, 1 H), 4.20–3.95 (m,
4 H), 2.34–2.14 (m, 4 H), 1.77 (dd, J = 14.4, 1.8 Hz, 3 H),
Synlett 2008, No. 13, 2017–2022 © Thieme Stuttgart · New York

2022
K. Tanaka et al.
LETTER
1.75–1.59 (m, 4 H), 1.34 (t, J = 7.2 Hz, 6 H). 13C NMR (75
MHz, CDCl3): d = 192.2, 154.0, 153.7, 140.9, 140.7, 135.6,
131.6, 129.2, 62.0, 61.9, 30.6, 21.7, 21.6, 21.2, 16.4, 16.3,
14.2, 14.1. 31P NMR (121 MHz, CDCl3): d = 20.3.
1.41 (m, 4 H), 1.26 (t, J = 7.2 Hz, 6 H). 13C NMR (75 MHz,
CDCl3): d = 191.6, 153.3, 153.0, 142.4, 142.2, 137.3, 135.9,
135.0, 134.4, 134.3, 128.6, 128.5, 128.4, 128.20, 128.17,
62.5, 62.4, 30.92, 30.90, 21.7, 21.0, 16.3, 16.2. 31P NMR
(121 MHz, CDCl3): d = 17.2.
Compound (Z)-3ha: pale yellow oil. 1H NMR (300 MHz,
CDCl3): d = 9.79 (s, 1 H), 6.70–6.60 (m, 1 H), 4.12–3.92 (m,
4 H), 2.35–2.15 (m, 4 H), 2.04 (dd, J = 13.2, 1.8 Hz, 3 H),
1.74–1.56 (m, 4 H), 1.28 (t, J = 7.2 Hz, 6 H). 13C NMR (75
MHz, CDCl3): d = 192.6, 155.6, 155.5, 141.0, 140.9, 135.1,
131.7, 129.3, 61.7, 61.6, 31.4, 21.8, 21.7, 21.6, 21.5, 21.1,
16.4, 16.3. 31P NMR (121 MHz, CDCl3): d = 17.6.
Compound (Z)-3hb: pale yellow oil. 1H NMR (300 MHz,
CDCl3): d = 9.93 (s, 1 H), 7.45–7.31 (m, 5 H), 7.08–6.88 (m,
1 H), 4.08–3.83 (m, 4 H), 2.50–2.38 (m, 2 H), 2.34–2.21 (m,
2 H), 1.75–1.64 (m, 4 H), 1.18 (t, J = 7.2 Hz, 6 H). 13C NMR
(75 MHz, CDCl3): d = 192.4, 155.5, 155.4, 144.4, 144.3,
138.5, 138.4, 137.7, 135.3, 135.17, 135.15, 128.3, 128.12,
128.05, 62.1, 62.0, 31.24, 31.21, 21.9, 21.7, 21.1, 16.2, 16.1.
31P NMR (121 MHz, CDCl3): d = 15.1.
Compound (E)-3hb: pale yellow oil. 1H NMR (300 MHz,
CDCl3): d = 9.85 (s, 1 H), 7.54 (d, J = 23.1 Hz, 1 H), 7.32–
7.13 (m, 5 H), 4.18–3.99 (m, 4 H), 2.16–2.00 (m, 4 H), 1.57–
Synlett 2008, No. 13, 2017–2022 © Thieme Stuttgart · New York