A rhodium(I)-catalyzed formal allenic Alder ene reaction for the rapid and stereoselective assembly of cross-conjugated trienes

Article abstract of DOI:10.1021/ja027588p

A rhodium(I)-catalyzed allenic Alder ene reaction to prepare cross-conjugated trienes has been discovered. The scope and limitations are currently being investigated, and the results obtained to date are reported on. This method shows enticing functional group compatibility by tolerating terminal and internal alkynes, hydroxyl, sulfonamide, ether, and diester groups. Progress has been made to increase the stereoselectivity of the olefinic side chain via an unprecendented iridium(I) catalyzed Alder-ene reaction. Copyright

Full text of DOI:10.1021/ja027588p

Published on Web 11/28/2002
A Rhodium(I)-Catalyzed Formal Allenic Alder Ene Reaction for the Rapid and
Stereoselective Assembly of Cross-Conjugated Trienes
Kay M. Brummond,* Hongfeng Chen, Peter Sill, and Lingfeng You
Department of Chemistry, UniVersity of Pittsburgh, Pittsburgh, PennsylVania 15260
Received July 8, 2002
Transition metal catalyzed carbon-carbon bond-forming pro-
cesses have revolutionized strategies used to increase molecular
complexity. Recently, Trost,1 Buchwald2 and Zhang3 have dem-
onstrated the feasibility of a transition metal-catalyzed formal Alder
ene reaction by effecting the formation of five-membered rings
possessing a 1,4-diene moiety from enynes. An analogous intra-
molecular allenic Alder ene reaction has received less attention due
to its requiring a regioselective reaction with the distal π-bond of
the allene.4 Malacria5 and Sato6 have both effected intramolecular
allenic Alder ene reactions, but the substrate-controlled constitu-
tional group selectivity is limiting. Furthermore, Livinghouse and
Oh have both observed cross-conjugated trienes in low yields during
transition metal-catalyzed reactions of alkynyl allenes, but no
follow-up studies have been reported.7 A cross-conjugated triene
is an interesting building block since it can participate in a variety
of tandem carbon-carbon bond-forming processes, such as Diels-
Alder reactions.8 It would seem then that the cross-conjugated
substructure would be ubiquitous, but in fact, few strategies are
available for its preparation with the majority of them relying on
classical synthetic methods.9
(CO)2Cl]2] but substitution of the carbon monoxide atmosphere with
nitrogen resulted in formation of cross-conjugated triene 5 in 72%
yield (eq 1). The exocylic olefin (vinyl silane) was obtained as the
E isomer exclusively evidenced by the observed nOe of 4.5%
between H1 and H2. The appending olefin was obtained as a mixture
1
of E:Z isomers (5:1) as determined by H NMR.
The mechanism most likely involves â-hydride elimination of
the intermediate rhodium metallocycle to afford the appending olefin
of 5, followed by a reductive elimination of a metallo-hydride
species to give the exocyclic olefin. The exclusive E-stereochemistry
of the exocylic olefin supports this mechanism. Furthermore, the
deuterated allenyne 6 affords triene 7 in 63% yield with complete
transfer of the deuterium (eq 2). A crossover experiment was
performed where a 1:1 mixture of 6 and 8 were subjected to
[Rh(CO)2Cl]2 in toluene at 90 °C and only trienes 7 and 9 were
obtained with no evidence of deuterium scrambling. An nOe of
1.3% was observed between X1 ) H and the CH3 on the appending
olefin.
Recently, while screening transition metals to mediate the allenic
Pauson-Khand reaction under milder conditions with higher
stereoselectivity, we discovered that 5 mol % rhodium biscarbonyl
chloride dimer [Rh(CO)2Cl]2 gave only the 4-alkylidene cyclopen-
tenones, resulting from selective reaction with the distal double
bond of the allene, independent of the allene substitution pattern
(Scheme 1).10 Typically strategies used to control allene constitu-
Scheme 1
The scope and limitations of this new method are currently being
investigated, and the results obtained to date are summarized in
Table 1. Treatment of allenyne 11 with 2 mol % [Rh(CO)2Cl]2 at
90 °C provided compound 12 in 80% yield with a 3:1, E:Z ratio
(entry 1, Table 1). Similarly, allenyne 13 possessing only a methyl
group on the distal position of the allene gave only triene 14 in
71% yield (entry 2, Table 1). Rh(COD)2Cl can also be used to
effect the allenic Alder ene in much faster reaction times, but this
catalyst does require an additive (entry 3, Table 1). Replacement
of the terminal alkyne with a TMS-alkyne also gives the trienes
but in somewhat lower yields (entries 4 and 5, Table 1). The
sulfonamide functionality is compatible with this method based
upon the conversion of allenynes 19, 21, and 23 to 20, 22, and 24,
respectively (entries 6-9, Table 1). Performing this reaction at room
temperature gives a higher yield of triene 20 with a slight increase
in E:Z selectivity (compare entries 6 and 7, Table 1). Ether-tethered
allenyne 25 gives only the triene 26 in 74% yield (entry 10, Table
tional group selectivity involve (1) differential substitution of the
allene termini, (2) intramolecularization, and (3) incorporation of
directing functional groups on the carbon adjacent to the allene.
This result constitutes a rare example of transition metal-directed
constitutional group selectivity of an allene and incentive for further
investigations involving other interesting carbon-carbon bond-
forming reactions.11
Since metallocycle 2 is an intermediate in the formation of the
4-alkylidene cyclopentenone 3 from alkynyl allene 1, it was
postulated that metallocycle 2 could serve as a diverging point for
other metal-catalyzed processes (Scheme 1). On the basis of this
hypothesis, reaction conditions were then adjusted to eliminate the
possibility of carbon monoxide insertion. To our delight, treatment
of alkynyl allene 4 to the standard Rh(I) conditions [2 mol % [Rh-
* To whom correspondence should be addressed. E-mail: kbrummon@pitt.edu.
9
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J. AM. CHEM. SOC. 2002, 124, 15186-15187
10.1021/ja027588p CCC: $22.00 © 2002 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Stereochemistry of Olefinic Side Chaina
Table 1. Examining the Scope of the Allenic Alder Ene Reactiona
entry
allenyne
triene
conditions
E/Z
yield (%)
1
2
3
4
5
6
7
4
4
4
4
15
23
31
5
5
5
5
16
24
32
A
5:1
13:1
4:1
>20:1
180:1c
>20:1
>99:1c
72
67
46
57
67
62
74
Bb
Cb
D
D
D
D
a Conditions: (A) 2 mol % [Rh(CO)2Cl]2, toluene, N2, 90 °C, 1 h. (B)
5 mol % [Rh(COD)Cl]2, 10 mol % AgSbF6, DCE, rt, 15 min. (C) 5 mol %
[Rh(CH2CH2)2Cl]2, 10 mol % AgSbF6, DCE, rt, 15 min. (D) 10 mol %
b
[Ir(COD)Cl]2, 20 mol % AgBF4, DCE, 60 °C, 5 min. Under these
conditions the silyl group was completely removed from the exocyclic olefin.
c E/Z ratio determined by GC analysis.
compound 25 and the substrates possessing terminal alkynes to these
iridium conditions gave only decomposition by crude NMR. In the
terminal alkyne case, the iridium most likely reacts with the acidic
alkyne proton to form a metal acetylide. Further studies from our
laboratory will be forthcoming which will elucidate the scope of
this stereoselective iridium allenic Alder ene reaction.
In conclusion, we have discovered a rhodium(I)-catalyzed allenic
Alder ene reaction that provides cross conjugated trienes in very
good yields. This method shows enticing functional group compat-
ibility, and progress has been made to increase the stereoselectivity
of the olefinic side chain via iridium(I) catalysis. We have
subsequently shown that these trienes can be used in tandem Diels-
Alder reactions, and these results will be reported on soon.
Acknowledgment. We gratefully acknowledge the funding
provided by the National Institutes of Health (GM54161), the
National Science Foundation and the University of Pittsburgh.
a Conditions: 2 mol % [Rh(CO)2Cl]2, toluene, N2. *5 mol [Rh(COD)Cl]2,
10 mol % AgSbF6. ( Reactions were run in CH2Cl2 or DCE; toluene gave,
on average, yields that were 15% lower.
1
Supporting Information Available: Experimental details and H
and 13C NMR spectra of all new compounds are available (PDF). This
material is available free of charge via the Internet at http://pubs.acs.org.
1). Finally, an unprotected hydroxymethyl group is well-tolerated
in the rhodium-catalyzed Alder ene reaction. Allenynes 27, 29, and
31 give high yields of the corresponding trienes 28, 30, and 32
(entries 11-13).
References
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citations 3 and 4 of this reference for other transition-metal-catalyzed Alder
ene reactions.
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The ability to control the stereochemistry of the olefinic side
chain is important if this method is to be applicable to target-
oriented synthesis and to gain a better understanding of the transition
metal-catalyzed Alder ene reaction. Allenyne 4 and [Rh(CO)2Cl]2
give triene 5 with an E:Z selectivity of 5:1 (entry 1, Table 2).
Allenyne 4 and [Rh(COD)Cl]2 along with 10 mol % of AgSbF6
additive provided the desilylated triene 5 in 67% yield with an E:Z
ratio of 13:1 (entry 2, Table 2). In contrast to the example in entry
1, this reaction was very fast at room temperature. Treatment of
allenyne 4 to 5 mol % [Rh(CH2CH2)2Cl]2 and 10 mol % AgSbF6
gave a 46% yield of desilylated triene 5 in an E:Z ratio of 4:1
(entry 3, Table 2). Moving down the periodic column to iridium
enhanced the selectivity, since subjecting allenyne 4 to 10 mol %
[Ir(COD)Cl]2 along with 20 mol % of AgBF4 additive provided
the triene 5 in 57% yield with an E:Z ratio of >20:1 as measured
by 1H NMR (entry 4, Table 1). Using these same iridium conditions,
compounds 15, 23, and 31 all afforded good yields of the trienes
with very high E:Z selectivities (entries 5, 6, and 7, Table 2). In
addition to the very high E:Z selectivities, this represents the first
iridium-catalyzed Alder ene reaction. However, treatment of
JA027588P
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J. AM. CHEM. SOC. VOL. 124, NO. 51, 2002 15187