Tandem Stille/Suzuki-Miyaura coupling of a hetero-bis-metalated diene. Rapid, one-pot assembly of polyene systems

Article abstract of DOI:10.1021/ol050768u

(Chemical Equation Presented) The synthesis of a hetero-bis-metallo 1,3-butadiene is reported, and its use as an orthogonal Stille and Suzuki-Miyaura coupling partner is detailed. The tin/boron diene participated successfully in a one-pot, sequential Stil

Full text of DOI:10.1021/ol050768u

ORGANIC
LETTERS
2005
Vol. 7, No. 11
2289-2291
Tandem Stille/Suzuki−Miyaura Coupling
of a Hetero-Bis-metalated Diene. Rapid,
One-Pot Assembly of Polyene Systems
Robert S. Coleman* and Matthew C. Walczak
Department of Chemistry, The Ohio State UniVersity, 100 West 18th AVenue,
Columbus, Ohio 43210
coleman@chemistry.ohio-state.edu
Received April 8, 2005
ABSTRACT
The synthesis of a hetero-bis-metallo 1,3-butadiene is reported, and its use as an orthogonal Stille and Suzuki
−Miyaura coupling partner is
detailed. The tin/boron diene participated successfully in a one-pot, sequential Stille and Suzuki−Miyaura coupling protocol, and its utility was
demonstrated in the two-step construction of the pentaene side chain of the Fusarium metabolite lucilactaene.
Palladium-catalyzed cross-coupling reactions are a tremen-
dously effectual tool in organic chemistry; it is difficult to
imagine the design and execution of complex molecule
syntheses in their absence. The Stille1 and Suzuki-Miyaura2
reactions are preeminent due to their compatibility with a
diverse range of functional groups and because of the ease
with which boron and tin can be incorporated into organic
molecules.
The synthesis of conjugated polyenes is of great interest
because of their wide occurrence in natural3 and unnatural
products.4 As part of an interest in the efficient and
stereodefined production of polyene systems,5 we have
developed a novel lynchpin system useful for construction
of biologically relevant polyenes. The easily prepared tin/
boron 1,4-bis-metallo-1,3-butadiene 1 was designed as a
differentially and orthogonally functionalized coupling part-
ner, which would permit stepwise and bidirectional elabora-
tion based on the intrinsic differential reactivity of the two
carbon-metal bonds. This reagent represents a prototypical
orthogonal Stille/Suzuki-Miyaura system.
Expanding the range of coupling partners for these
reactions is an important undertaking, and we report the
synthesis of hetero-bis-metalated 1,3-butadiene 1 (Figure 1)
Other reported hetero-bis-metalated systems include a
well-known tin/silicon alkene6 and a single report of a vinylic
boron/tin system.7 Several homo-bis-metalated olefins are
well-known, including those of tin8 and boron.9
Herein, we report orthogonal coupling conditions that
allow selective coupling at the differentially metalated termini
Figure 1. Hetero-bis-metalated butadiene.
(2) (a) Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457. (b) Stanforth,
S. P. Tetrahedron 1998, 54, 263. (c) Suzuki, A. J. Organomet. Chem. 1999,
576, 147.
(3) Thirsk, C.; Whiting, A. J. Chem. Soc., Perkin Trans. 1 2002, 8, 999.
(4) Krasnaya, Zn. A.; Tatikolov, A. S. Russ. Chem. Bull., Int. Ed. 2003,
52, 1641.
and demonstrate its utility in the rapid, one-pot construction
of archetypal polyene systems.
(1) (a) Stille, J. K.; Milstein, D. J. Am. Chem. Soc. 1978, 100, 3636. (b)
Stille, J. K. Angew. Chem., Int. Ed Engl. 1986, 25, 508. (c) Farina, V. Pure
Appl. Chem. 1996, 68, 73. (d) Farina, V.; Krishnamurthy, V.; Scott, W. J.
Org. React. 1997, 50, 1.
(5) (a) Coleman, R. S.; Garg, R. Org. Lett. 2001, 3, 3487. (b) Coleman,
R. S.; Liu, P.-H. Org. Lett. 2004, 6, 577.
(6) Murakami, M.; Matsuda, T.; Itami, K.; Ashida, S.; Terayama, M.
Synthesis 2004, 1522.
10.1021/ol050768u CCC: $30.25
© 2005 American Chemical Society
Published on Web 04/23/2005

of 1. In addition, we report a one-pot sequential Stille/
Suzuki-Miyaura coupling sequence10 as a valuable attribute
of 1. Application of this methodology to biologically relevant
systems is illustrated by the rapid construction of the side
chain of lucilactaene (Figure 2).11
Table 1. Stille Coupling Reactions of 1
Figure 2. Structure of Fusarium metabolite lucilactaene.
Butadiene 1 was effectively synthesized from propargal-
dehyde diethyl acetal (2) by stannylcupration12 followed
directly by acetal hydrolysis to afford â-stannylacrolein 3.13
Takai olefination with dichloromethylborinate 4 afforded
butadiene 1 in yields routinely above 75% (Scheme 1).
Scheme 1. Preparation of Butadiene 1
a Key: (A) Pd2dba3 (1.5 mol %), P(furyl)3 (3.5 mol %), NMP, 23-50
°C; (B) PdCl2(CH3CN)2 (5 mol %), DMF, 25 °C. b Isolated yield (average
of two runs).
Table 2. Suzuki-Miyaura Coupling Reactions of 10
Selective Stille coupling at the tin-bearing terminus of 1
was possible because of the need for basic reaction conditions
to effect transmetalation at the boron-bearing end. Bromides,
iodides, and triflates all effectively participated in Stille
coupling reactions with 1 (Table 1).
There was little difference in yield between electron-
deficient aryl bromide 5 (entry 1) and iodide 7 (entry 2),
although aryl triflate 8 (entry 3) provided modest yields of
coupled product 6. Electron-rich aryl iodides 9 (entry 4) and
11 (entry 5), and sterically crowded 2,6-dimethyl substituted
(7) Lhermitte, F.; Carboni, B. Synlett 1996, 377.
(8) Echavarren, A. M.; Stille, J. K. J. Am. Chem. Soc. 1988, 110, 1557.
Renaldo, A. F.; Labadie, J. W.; Stille, J. K. Org. Synth. 1989, 67, 86.
(9) Ishiyama, T.; Matsuda, N.; Miyaura, N.; Suzuki, A. J. Am. Chem.
Soc. 1993, 115, 11018.
(10) (a) Ogima, M.; Hyuga, S.; Hara, S.; Suzuki, A. Chem. Lett. 1988,
809. (b) Ogima, M.; Hyuga, S.; Hara, S.; Suzuki, A. Chem. Lett. 1989,
1959. (c) Meijere, A.; Zezschwitz, P.; Nu¨ske, H.; Stulgies, B. J. Organomet.
Chem. 2002, 653, 129.
(11) Kakeya, H.; Kageyama, S.-I.; Nie, L.; Onose, R.; Okada, G.; Beppu,
T.; Norbury, C. J.; Osada, H. J. Antibiot. 2001, 54, 850.
(12) Lipshutz, B. H.; Lindsley, C. J. Am. Chem. Soc. 1997, 119, 4555.
Lipshutz, B. H.; Ullman, B.; Lindsley, C.; Pecchi, S.; Buzard, D. J.; Dickson,
D. J. Org. Chem. 1998, 63, 6092.
(13) A route to 3 involving hydrostannylation of propargyl alcohol was
less reproducible because a poor and variable E/Z ratio was obtained.
a Key: (C) (Ph3P)4Pd (5 mol %), 2 M aq K2CO3, toluene/EtOH, 23-60
°C; (D) Pd2dba3 (1.5 mol %), P(furyl)3 (3.5 mol %), CsF, NMP, 23 °C; (E)
(Ph3P)4Pd (5 mol %), K3PO4, dioxane, 85 °C. b Isolated yield (average of
two runs).
2290
Org. Lett., Vol. 7, No. 11, 2005

iodide 13 (entry 6) both provided excellent yields of products
10, 12, and 14, respectively. Iodoacrylic acid (15, entry 7)
was an effective partner, as were cis- and trans-1-iodo-1-
hexene (entry 8). In comparison to aryl triflate 8 (entry 3),
enol triflate 19 (entry 9) could be coupled with 1 in excellent
yield.14 Reactions generally proceeded quantitatively, with
no evidence of competing reaction of the vinyl borinate.
Subsequential Suzuki-Miyaura coupling the borinate 10
was effectively achieved with various partners (Table 2). Aryl
iodide 21 provided the highest yield of coupled product (entry
1), significantly higher than the comparable bromide 23
(entry 2). Yields were also lower for sterically crowded
iodide 13 (entry 3) and electron rich system 9 (entry 4).
Phenyl triflate (27) coupled effectively (entry 5), but enol
triflate 19 was not an effective partner (entry 6). Stereoiso-
meric vinyl iodides 17 participated effectively (entry 7).
Tandem coupling of 1 was implemented in a sequential
one-pot sequence, performing the Stille coupling with one
partner followed by direct addition of CsF and the second
coupling partner to the reaction flask to effect Suzuki-
Miyaura coupling. This one-pot, sequential Stille/Suzuki-
Miyaura coupling could be achieved in excellent overall yield
in the formation of 31 and 32 (Scheme 2).
tandem coupling protocols. Dienyl iodide 3315 was coupled
with 1 under Stille conditions to afford tetraene 34. Subse-
quent Suzuki-Miyaura coupling with â-iodoacrylate 35
afforded the lucilactaene pentaene fragment 36 in nearly 50%
overall yield for the two sequential coupling reactions
(Scheme 3).
Scheme 3. Assembly of Lucilactaene Pentaene Side Chain
The one-pot, two-directional coupling by sequential Stille
and Suzuki-Miyaura couplings clearly shows the potential
of this reagent and strategy. The utility of 1 as a lynchpin
reagent was demonstrated in an efficient two-step coupling
to form the pentaene side chain of the Fusarium metabolite
lucilactaene. This novel reagent system demonstrates the
potential of orthogonal Stille and Suzuki-Miyaura coupling
protocols in synthesis.
Scheme 2. One-pot Sequential Stille/Suzuki-Miyaura
Coupling with Butadiene 1
Acknowledgment. This work was supported by a grant
from the National Cancer Institute (NIH CA91904).
Supporting Information Available: Experimental pro-
cedures and characterization of compounds. This material
is available free of charge via the Internet at http://pubs.acs.org.
OL050768U
(14) Isolated yields were lowered because of the difficulty of purifying
vinyl boronates. Chromatography with Florosil gave higher yields than with
silica.
Use of 1 in the synthesis of the pentaene side chain of
lucilactaene clearly demonstrates the potential for orthogonal,
(15) Coleman, R. S.; Walczak, M. C. Unpublished studies.
Org. Lett., Vol. 7, No. 11, 2005
2291