Platinum-catalyzed divergent reactivity of α-hydroxyallenes: Synthesis of dihydrofurans and α,β-unsaturated ketones

Article abstract of DOI:10.1002/adsc.201300413

α-Allenols were catalytically transformed into dihydrofurans in the presence of platinum dichloride. Notably, using platinum dichloride along with silver triflate as the catalytic system, α,β-unsaturated ketones were obtained. Therefore, the role of the s

Full text of DOI:10.1002/adsc.201300413

UPDATES
DOI: 10.1002/adsc.201300413
Platinum-Catalyzed Divergent Reactivity of a-Hydroxyallenes:
Synthesis of Dihydrofurans and a,b-Unsaturated Ketones
Benito Alcaide,a,* Pedro Almendros,b,* Israel Fernꢀndez,c
Teresa Martꢁnez del Campo,a and Teresa Naranjoa
a
Grupo de Lactamas y Heterociclos Bioactivos, Departamento de Quꢁmica Orgꢀnica I, Unidad Asociada al CSIC, Facultad
de Quꢁmica, Universidad Complutense de Madrid, 28040 Madrid, Spain
Fax : (+34) 91-394-4103; e-mail: alcaideb@quim.ucm.es
Instituto de Quꢁmica Orgꢀnica General, IQOG, Consejo Superior de Investigaciones Cientꢁficas, CSIC, Juan de la Cierva
b
3, 28006 Madrid, Spain
Fax : (+34) 91-5644853; e-mail: Palmendros@iqog.csic.es
Departamento de Quꢁmica Orgꢀnica I, Facultad de Quꢁmica, Universidad Complutense de Madrid, 28040 Madrid, Spain
c
Received: May 10, 2013; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201300413.
Abstract: a-Allenols were catalytically transformed
into dihydrofurans in the presence of platinum di-
chloride. Notably, using platinum dichloride along
with silver triflate as the catalytic system, a,b-unsa-
turated ketones were obtained. Therefore, the role
of the silver salt may not just consist in the activa-
tion of the platinum precatalyst.
develop catalytic systems employing platinum salts
and silver additives.
Allenes, a class of compounds with two cumulative
carbon-carbon double bonds, are versatile synthetic
intermediates in organic synthesis.[3] Following up on
our combined interest in the area of metals and al-
lenes,[4] we have recently communicated the gold-cat-
alyzed synthesis of oxetenes through rare 4-exo-dig
allene cyclization of salicylaldehyde-derived a-alle-
nols [Scheme 1, Eq. (1)].[5]
Keywords: allenes; heterocycles; homogeneous cat-
alysis; platinum; regioselectivity
In contrast to gold catalysis,[6,7] the platinum-cata-
lyzed reactions using allenols as substrates constitute
an almost unexplored field of noble metal catalysis.
Platinum salts have been used for the oxycyclization
The use of gold and platinum salts has gained a lot of of b-allenols and g-allenols,[8–10] but not for the oxy-
attention in the recent times because of their power- cyclization of a-allenols. The only report on the Pt-
ful soft Lewis acidic nature. The employment of silver catalyzed reaction of a-allenols is the carbocyclization
additives is a common practice to enhance the activity rather than the oxycyclization of 1-(indol-2-yl)-2,3-al-
of the gold catalyst.[1,2] By contrast, it is challenging to lenols to provide substituted carbazoles.[11] Taking
into account the analogies in the catalytic behavior of
Scheme 1. Divergent reactivity of allenols under gold and platinum catalysis.
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Au and Pt compounds, we decided to study the reac- tuted dihydrofurans 2b–h in good yields within ac-
tivity of a-hydroxyallenes under platinum catalysis. ceptable reaction times (Scheme 2). The above results
We wish to report here that the reaction outcome for indicate that the Pt-catalyzed reaction shows comple-
the platinum-catalyzed reactions of allenols sharply mentarity with the Au-catalyzed process.
contrasts to that of gold catalysis,[12] because the prep-
After identifying an appropriate catalyst for the
aration of both dihydrofurans and a,b-unsaturated ke- oxycyclization reaction, we optimized other critical
tones via platinum catalysis can be efficiently con- reaction parameters, such as the addition of additives.
trolled [Scheme 1, Eq. (2)].
No benefit occurs across the addition of a phosphine,
Our initial studies concentrated on the platinum- because the use of PtCl2 in the presence of tris(2,6-di-
catalyzed cyclization reaction of a-allenol 1a. Nicely, methoxyphenyl)phosphine gave dihydrofurans 2 in
it was found that PtCl2 or [PtCl2ACHTNUGRTNEUNG(CH2=CH2)]2 were similar yields. In particular, the transformation was
competent catalytic systems for this purpose. Solvent strongly influenced by the presence of a silver-based
screening demonstrated that dichloromethane was the additive. To our surprise, a complete switch of the re-
best choice in the reaction. 1 mol% of PtCl2 provided activity was observed when using silver in the process.
dihydrofuran 2a in 64% yield after reacting overnight Gratifyingly, it was found that a-allenol 1a on expo-
at room temperature in dichloromethane. Notably, sure to the system PtCl2 (1 mol%)/AgOTf (2 mol%)
platinum-based catalysis favors a 5-endo-trig pathway, in dichloromethane at room temperature for 5 h, di-
while our previous report on gold-based catalysis af- rectly afforded a,b-unsaturated ketone 3a through
forded an oxetene through 4-exo-dig cyclization.[5] a rearrangement process. Changes on the nature of
Thus, complete selectivity can be achieved by using the counterion had little effect in the reaction, be-
both Au- and Pt-based catalysis. To evaluate the gen- cause alternate counterions (AgSbF6, AgBF4) showed
eral applicability of this cycloisomerization protocol, a minimal effect to improve the yield of the product.
a series of aryl- or methyl-substituted allenol deri- We also found that the rearrangement adduct 3a
vates 1b–h was oxycyclized under the same reaction could be obtained in the presence of 1 mol% PtCl2
conditions. All of the reactions delivered the substi- and 1 mol% AgOTf (Scheme 3). The above catalytic
system was applicable to a variety of allenol deriva-
tives 1b–h. Thus, starting from 1a–h the reaction af-
forded the linear adducts 3a–h in 41–84% yields with
an E/Z stereoselectivity of 0:100–100:0 as deduced
1
from H NMR analysis of the crude reaction mixtures
(Scheme 3). Interestingly, adducts 3a, 3f, 3g, and 3h
were exclusively formed as E-alkenes, while Z-3e was
achieved as a single isomer. Fortunately, for alkenes
3b–d the E- and Z-isomers were chromatographically
separable, which allows the isolation of the thermody-
namically less stable Z-alkenes. Interconversion of the
isolated Z form of adducts 3c and 3d into the E con-
figuration spontaneously occurs after several days at
room temperature.
Noticeably, despite the above ability (Scheme 2) of
platinum-based catalysis for the cycloetherification of
Scheme 2. Platinum-catalyzed cycloisomerization of allenols
1.
Scheme 3. Platinum-catalyzed rearrangement of allenols 1.
2
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Platinum-Catalyzed Divergent Reactivity of a-Hydroxyallenes: Synthesis of Dihydrofurans
a-allenols 1 to dihydrofurans 2, no traces of heterocy-
cles were detected using a silver salt as additive
(Scheme 3). After control experiments it was demon-
strated that the silver salt alone does not catalyze the
reaction of interest, and a major part of allenol 1 was
recovered unaltered. Thus, it may be safely assumed
that the role of the silver salt just consists in the acti-
vation of the platinum precatalyst. However, despite
proving that the silver activator itself is unreactive,
we decided to study how the Ag(I) additive affected
the reactivity of the platinum(II)-catalyzed reaction.
A hypothetical Pt-based species free of silver was
prepared by premixing for a few minutes PtCl2/
AgOTf (1:1) in dichloromethane under Schlenk con-
ditions, followed by filtration through a pack of dry
Celite.[13] Thus, a direct comparison of the reactivity
with or without the presence of AgCl may be carried
out. Worthy of note, the above Pt-based catalyst
could not promote the rearrangement reaction of alle-
Scheme 4. Mechanistic explanation for the platinum-cata-
nol 1f, giving instead the cycloisomerization adduct
2f. However, when the mixture of PtCl2 and AgOTf
was used directly (without filtration of AgCl), the re-
action worked as described in Scheme 3. Interestingly,
a mixture of the Pt-based complex obtained from fil-
tration through Celite and AgOTf promoted the rear-
rangement reaction effectively, which suggested that
the combination of platinum and silver made the a,b-
unsaturated ketone formation possible. These joined
experiments point to the crucial role of silver addi-
tives in the platinum-catalyzed reaction of a-allenols.
Unfortunately, we were unable to get a crystal struc-
ture of the catalyst.
lyzed cycloetherification of allenols 1.
All the successful a,ß-unsaturated ketone forma-
tions occurred from 2-alkoxy-substituted a-hydroxyal-
lenes 1. It is possible that the 2-alkoxy group repre-
sents the optimal balance in its ability to both give
a good conversion in a reasonable time and coordi-
nate to any metallic species, avoiding the five-mem-
bered ring formation.
The achievement of dihydrofurans 2 involving
a platinum-based carbophilic p-acid very likely pro-
ceeds through a similar reaction mechanism to that
reported by us for the gold-catalyzed oxycyclization
of allenols.[5] Thus, the initial h-coordination of the
metal to the distal double bond of allenols 1 leads to
Scheme 5. Mechanistic explanation for the platinum-cata-
lyzed rearrangement of allenols 1.
species 1-Pt, which undergoes a 5-endo-trig alkoxypla- ment process instead of oxacycles via the usually pre-
tination to form zwitterionic dihydrofurans 4. Loss of ferred gold- or platinum-catalyzed cycloetherification
HCl in intermediates 4 generates neutral vinylmetal reactions. Although speculative at the present
species 5. Finally, protonolysis of the carbon-platinum moment, the pathway proposed in Scheme 5 could be
bond of 5 liberates dihydrofurans 2 with concomitant feasible. It could be presumed that the initially
regeneration of the Pt(II) catalytic species formed metallic complex 6, through coordination of
(Scheme 4).
the metal to the distal allenic double bond of allenols
A mechanistic rationale for the platinum-catalyzed 1, undergoes a 4-exo-dig metala-oxycyclization, giving
conversion of a-allenols 1 into a,b-unsaturated ke- rise to the oxetene intermediates 7. Heterocycle ring
tones 3 is more intricate. It is worth noting that the opening in intermediates 7 through an electrocyclic
platinum-catalyzed reaction in the presence of the reaction generates zwitterionic a,b-unsaturated ke-
silver additive affords adducts 3 through a rearrange- tones 8. Subsequent demetalation linked to proton
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Benito Alcaide et al.
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transfer liberates adducts 3, closing the catalytic cycle all the experiments into account, in particular the
and releasing the catalytic species (Scheme 5). transformation of oxetene 9 into a,ß-unsaturated
To shed light on the active participation of the al- ketone 3b, the Meyer–Schuster-type rearrangement
lenic alcohol moiety in the transformation from 1 to seems very unlikely.
3, an 18O-labeling experiment was initiated. Mass
In conclusion, a-allenols were transformed into di-
spectrometric analysis of the product of reaction of al- hydrofurans in the presence of PtCl2, while using
lenol 1f under PtCl2-AgOTf catalysis in the presence PtCl2 along with AgOTf as the catalytic system, a,b-
of 100 mol% H218O, showed that the a,b-unsaturated unsaturated ketones were obtained. This divergent re-
ketone 3f (obtained in a diminished yield of 25%) activity points to an important role of the silver salt in
was not 18O-labeled, revealing that the carbonylic the activation of the platinum precatalyst.
oxygen atom was not coming from external H2O.
With the aim of trapping a possible organometallic in-
termediate in order to understand the mechanism of
this reaction, we performed deuterium labeling stud-
ies with deuterium oxide as well. Under the same
Experimental Section
conditions as above but with the addition of one
equivalent of D2O, the rearrangement reaction of al-
lenol 1f catalyzed by PtCl2-AgOTf in dichlorome-
Typical Procedure for the Platinum-Catalyzed
Rearrangement Reaction of a-Allenols 1; Synthesis
of a,b-Unsaturated Ketone 3a
thane afforded product (E)-[D]-3f in a low 24% yield
PtCl2 (0.0108 mmol) and AgOTf (0.0108 mmol) were se-
with 33% deuterium content, suggesting that deuter-
quentially added to a stirred solution of the allenol 1a
(300 mg, 1.08 mmol) in dichloromethane (1.08 mL) under
olysis of the carbon-metal bond in an intermediate
species has occurred (Scheme 6). The mechanism pro-
argon. The resulting mixture was stirred at room tempera-
posed in Scheme 5 is consistent with the above iso-
ture under argon atmosphere until disappearance of the
starting material (TLC). The reaction was then quenched
tope-labeling experiments. We also decided to submit
oxetene compounds to the Pt-Ag-catalyzed reaction
with brine (1.0 mL), the mixture was extracted with ethyl
conditions to demonstrate their intermediacy in this
acetate (3ꢃ5 mL), and the combined extracts were washed
twice with brine. The organic phase was dried (MgSO4),
novel reaction. Consequently, oxetene 9 was allowed
to react with the catalytic system PtCl2-AgOTf. The concentrated under reduced pressure, and purified by flash
column chromatography on silica gel (hexanes/ethyl ace-
reactions did form a,b-unsaturated ketone (E)-3b in
moderate yield (Scheme 6); thus demonstrating the
intermediacy of oxetene species. By contrast, when di-
hydrofuran 2b was used as the substrate (under other-
wise identical conditions) a,b-unsaturated ketone 3b
was not formed.
tate=7:1) to afford product 3a as a colorless oil; yield:
1
168 mg (56%). H NMR (300 MHz, CDCl3, 258C): d=7.98
(s, 1H), 7.26 (m, 3H), 7.08 (dt, 3H, J=7.8, 1.7 Hz), 6.77 (d,
1H, J=8.2 Hz), 6.58 (d, 1H, J=7.8 Hz), 6.50 (t, 1H, J=
7.5 Hz), 6.03 (m, 1H), 5.40 (dq, 1H, J=17.3, 1.3 Hz), 5.26
(dq, 1H, J=10.5, 1.4 Hz), 4.54 (td, 2H, J=5.0, 1.5 Hz), 2.33
(s, 3H); 13C NMR (75 MHz, CDCl3, 258C): d=199.8, 157.6,
141.1, 136.7, 134.5, 133.2, 130.8, 130.5, 130.0 (2C), 128.8
(2C), 127.8, 120.3, 117.7, 112.1 (2C), 69.3, 27.7; HR-MS
Initially,
a mechanistic scenario that involves
a direct intramolecular 1,3-shift of the OH group
(analogous to the Meyer–Schuster rearrangement)
cannot be completely ruled out.[14] However, taking (ES): m/z=278.1314, calcd. for C19H18O2 [M]+: 278.1307.
Scheme 6. Labeling and control experiments.
4
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Platinum-Catalyzed Divergent Reactivity of a-Hydroxyallenes: Synthesis of Dihydrofurans
Chem. Commun. 2013, 49, 1282; c) B. Alcaide, P. Al-
mendros, J. M. Alonso, I. Fernꢀndez, Chem. Commun.
Acknowledgements
2012, 48, 6604.
Support for this work by the MINECO [Projects CTQ2012-
33664-C02–01, CTQ202-33664-C02–2, CTQ2010-20714-C02-
01, and Consolider-Ingenio 2010 (CSD2007-00006)], and
CAM (Projects S2009/PPQ-1752 and S2009/PPQ-1634) is
gratefully acknowledged. T. N. thanks Comunidad Autꢀnoma
de Madrid and Fondo Social Europeo for a predoctoral con-
tract.
[5] B. Alcaide, P. Almendros, T. Martꢁnez del Campo, I.
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a Pt
through Celite should allow the majority of the Pt-
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6 Platinum-Catalyzed Divergent Reactivity of a-
Hydroxyallenes: Synthesis of Dihydrofurans and a,b-
Unsaturated Ketones
Adv. Synth. Catal. 2013, 355, 1 – 6
Benito Alcaide,* Pedro Almendros,* Israel Fernꢀndez,
Teresa Martꢁnez del Campo, Teresa Naranjo
6
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