Catalytic use of a soluble organoindium(III) species for allylation and crotylation of ketones with boronates

Article abstract of DOI:10.1002/adsc.201000097

The unprecedented use of a soluble organoindium species, indium(III) hexamethyldisilazide [In(III)(hmds)₃], for catalytic carbon-carbon bond formations between ketones and boronates, is reported. Various functionalized tertiary homoallyl alcoho

Full text of DOI:10.1002/adsc.201000097

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DOI: 10.1002/adsc.201000097
Catalytic Use of a Soluble Organoindium(III) Species for
G
Allylation and Crotylation of Ketones with Boronates
Miyuki Yamaguchi,a Naohide Morita,a Uwe Schneider,a and Shu¯ Kobayashia,*
a
Department of Chemistry, School of Science, The University of Tokyo, The HFRE Division, ERATO, Japan Science and
Technology Agency (JST), Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
Fax : (+81)-3-5684-0634; phone: (+81)-3-5841-4790; e-mail: shu_kobayashi@chem.s.u-tokyo.ac.jp
Received: February 5, 2010; Revised: April 14, 2010; Published online: May 11, 2010
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201000097.
Abstract: The unprecedented use of a soluble orga-
noindium species, indium(III) hexamethyldisilazide
[In(III)(hmds)3], for catalytic carbon carbon bond
sulting tertiary homoallyl alcohols have proved to be
versatile intermediates and building blocks.[2] Typical
protocols for ketone allylation involve the use of
Barbier-type allylindium (In) species, generated in
situ from allyl halides, with a stoichiometric amount of
In(0) or In(I).[3] Catalytic methods include allyl stan-
nations employing InIII[4] or other[5] Lewis acids. With
the aim of avoiding toxic stannanes, important advan-
ces have been achieved through allyl silylations using
transition metal catalysts.[6] More recently, allyl bora-
tions employing transition metal catalysts[7] or metal-
free conditions[8] have been reported. As part of our
research program concerns the use of non-toxic re-
agents and catalysts, we have become interested in the
main group metal indium, as it has a low toxicity, is
inexpensive, safe, and selective, and is tolerant toward
functional groups.[9] While conventional inorganic
AHCTUNGTRENNUNG
ꢀ
G
ACHTUNGTRENNUNG
formations between ketones and boronates, is re-
ported. Various functionalized tertiary homoallyl al-
cohols were generated easily in high yields. Re-
markably, free hydroxy and primary amine func-
tionalities proved to be tolerated. A rate accelera-
tion and markedly improved diastereoselectivities
were observed in the presence of methanol. Based
on preliminary NMR experiments and the a-selec-
tivity with an a-substituted boronate, we assume
the in situ generation of reactive allylindiumACTHNUGTRNEUNG(III)
species through catalytic boron-to-indium transme-
talation.
ꢀ
Keywords: boron; C C bond formation; indium; si-
lazides; transmetalation
In
In
N
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
[9]
ꢀ
ious C C bond formations, InACHTGNUTRENNUNG
allylation typically requires the use of toxic stannanes
(Scheme 1a).[4] In the postulated mechanisms, the In-
Ketone allylation is among the most challenging[1] and
ACHTUNGTREN(NGNU III) catalyst may: (i) act as a Lewis acid to activate
useful transformations in organic synthesis. The re- the ketone for addition of the nucleophilic allylstan-
Scheme 1. (a) and (b) Precedents for In
Key: pin=pinacolyl.
ACHTUNGTRNE(NUNG III)-catalyzed carbonyl allylation, and (c) working hypothesis for the present study.
Adv. Synth. Catal. 2010, 352, 1461 – 1465
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Table 1. InACTHNUGTRNEUNG(III)-catalyzed allylation of 1a with 2.
[a]
Isolated yields of 3a after purification on silica gel (PTLC). ND=not detect-
ed.
Although full consumption of 1a was observed, the reaction mixture proved to
be messy with the formation of several undesired products, among which was
the diallylated by-product of 1a.
[b]
[c]
Concentration of 1a in toluene: 2M.
nane,[4b–e] or (ii) trigger Sn-to-In transmetalation with whereas In
ACTHNUTRGNEG(NU III)Cl3 as the most widely used indium
the resulting allylindium species being the real nucle- source, provided 3a in only 19% yield (entry 2). The
ophile.[4a] Non-toxic boronates are significantly less re- latter result may be ascribed either to the poor B-to-
active, and require Lewis acid or base activation.[10] In transmetalation ability of this indium catalyst, or to
The use of classic In
tion of carbonyl compounds has only been reported
with aldehydes (Scheme 1b).[11] Indeed, in our earlier acid In
studies on In(I) and In(0),[12] compounds such as In- formed, among which was the undesired diallylated
(III)(OTf)3 and In(III)I3 proved to be ineffective in by-product of 1a (entry 3). Therefore, we hypothe-
ketone allyl borations. These conventional, inorganic sized that the ideal In(III) catalyst should have: (i) a
indium(III) salts seem either not to promote B-to-In more Lewis basic ligand or counteranion X with a
transmetalation,[11] or do so only sluggishly.[12] In- higher boron affinity to promote efficient B-to-In
trigued by these observations, and being aware that transmetalation (=hard-hard interaction, cf.
(III) is more stable than In(I),[12] we sought a novel Scheme 1c), and (ii) an attenuated Lewis acidity to
(III) catalyst that was capable of catalyzing ketone suppress overreactions. Thus, we examined In(III)F3
(III)(OH)3 (entries 4 and 5); the disappointing
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
A
ACHTUNGTRENNUNG
A
R
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
ACHTUNGTRENNUNG
In
In
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
allylations using non-toxic boronates (Scheme 1c). and InACHTUNGTRENNUNG
The ideal catalyst would activate electrophilic allyl results may be explained by the low solubility of
boronates: (i) as a s-Lewis base (coordinated to the these inorganic metal salts. Therefore, we employed
(hmds)3],[13]
Lewis acidic boron atom=hard-hard interaction), and indiumACHTUNGTRENNN(UG III) hexamethyldisilazide [InAHCTUNRTGEG(NNUN III)ACHTNUGTRENNGUN
(ii) as a p-Lewis acid (coordinated to the C=C double an indium amide source with a substantially higher
bond=soft-soft interaction), to generate in situ nucle- solubility in organic solvents. Gratifyingly, the catalyt-
ophilic allylindium
tion). Here, we report an unprecedented use of a yield (71%, entry 6). To the best of our knowledge,
soluble organoindium species, indium(III) hexame- this result represents the first example of
thyldisilazide [In(III)(hmds)3], for catalytic activation In(III)(hmds)3 being used as a catalyst for organic syn-
of boronates for allylation and diastereoselective cro- thesis.[14] Further improvement was achieved by using
tylation of ketones. dry methanol (20 mol%) as an additive (entries 7–10),
ACHTUNGTRNE(NUNG III) species (B-to-In transmetala- ic use of this compound provided 3a in a promising
AHCTUNGTRENNUNG
A
E
N
ACHTUNGTRENNUNG
Initial experiments were conducted using the reac- resulting in a shorter reaction time (6 h), even with a
tion between acetophenone (1a) and allyl boronate 2 catalyst loading of only 2 mol% (entry 9). It should
as model (Table 1). Various InACHTNUTRGNE(NUG III) catalysts (5 mol%) be noted that the catalyst loading could be reduced to
were screened in dry toluene at room temperature for as little as 1 mol% under more concentrated condi-
12 h. As expected, the uncatalyzed reaction did not tions with an extended reaction time (entry 10).
proceed under the conditions employed (entry 1),
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Catalytic Use of a Soluble OrganoindiumACTHUNGTRENNUNG
Table 2. Scope of the InACHTUGNTRENNNUG
[a]
Isolated yields of 3b–s after purification on silica gel (PTLC).
[b]
[c]
Reaction conditions: In
N
ACHTUNGTRENNUNG
Reaction conditions: In
N
ACHTUNGTRENNUNG
Next, we investigated the scope for ketones (Table 3). In the absence of methanol, this catalytic
ꢀ
ꢀ
(Table 2). The present catalytic carbon carbon bond C C bond formation proceeded slowly to give the de-
formation proceeded smoothly with various acyclic or sired a-adduct 5a exclusively in 49% yield, albeit with
cyclic aromatic, heteroaromatic, and aliphatic ketones. a poor diastereomeric ratio (syn:anti=1.3:1; entry 1).
Furthermore, we consider the compatibility of the In- It is noteworthy that g-addition of 4 was not detected.
ꢀ
ꢀ
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
4
Table 3. InACTHNUGRTNEUNG(III)-catalyzed crotylation of 1a with 4.
[a]
Isolated yields of 3a after purification on silica gel (PTLC).
The diastereomeric ratios were determined by H NMR spectroscopic
[b]
1
analysis of the corresponding isolated product 5a.
Concentration of 1a in toluene: 2M.
[c]
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tries 3 and 4). The diastereomeric ratio of 5a was im- the corresponding crotylindium reagent, which may
proved markedly by increasing the amount of metha- then react with uncoordinated 1a in a cyclic Zimmer-
nol progressively to 500 mol% (syn:anti=13.3:1; man–Traxler-type transition state to give 5a with high
entry 7). Finally, slightly modified conditions provided syn:anti ratios (cf. Table 3, entries 6–8). Alternatively,
5a in 87% yield with a syn:anti ratio of 11.5:1 In
N
ACHTUNGTERNN(UNG hmds)3 may undergo ligand exchange via alco-
(entry 8).
The practical potential of this new In
catalyst was demonstrated through the highly selec-
tive crotylation of several ketones (Table 4). It is first catalytic use of a main group 13 metal amide, In-
noted that in all cases (i) g-adducts were not observed, (III)
(hmds)3, in organic synthesis.[14] The catalytic
and (ii) the desired a-products 5 were isolated in high carbon carbon bond formations between ketones and
yields with high syn-diastereoselectivity. boronates proceeded under very mild conditions in
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
ꢀ
From a mechanistic point of view, the rare, exclu- high yields with exclusive regioselectivity (a) and
sive a-selectivity observed with allyl boronate 4 high configurational selectivities (syn). The most char-
strongly suggests a B-to-In transmetalation.[15] In this acteristic features of this novel organoindium
ACTHUNTGRENNG(U III) spe-
context, it should be noted that the corresponding cies are: (i) its remarkable solubility in organic sol-
(E)- and (Z)-crotyl boronates were shown to react vents, (ii) its excellent p-Lewis acidity for B-to-In
only very sluggishly with 1a, which is most likely due transmetalation, and (iii) the high reactivity of the
to steric hindrance (methyl group) at the g-position corresponding in situ generated allylindium species.
during the transmetalation step. 1H and 11B NMR Significantly, in the context of ketone allylation, the
spectroscopic analysis of 2 or 4 in the presence of In- new In
ACHTUNGTREN(NUNG III) amide catalyst allows one to replace toxic
A
ACHTUNGTRENNUNG
particularly slow B-to-In transmetalation. Therefore, being directed toward further mechanistic studies, an
the initially intended transmetalation process (cf. asymmetric version, and novel transformations cata-
Scheme 1c) seems to be unlikely. At present, we be- lyzed by this unique indium
lieve that, in the absence of methanol, ketone 1a (as a
ACHTUNGTREN(NGNU III) Lewis acid.
Lewis base) may activate 4, resulting in the formation
of the corresponding crotylindium amide species, and Experimental Section
boron-activated 1a. The crotylindium intermediate
may add to the activated electrophile in an acyclic General Procedure
transition state to provide 5a with a low diastereose-
lectivity (cf. Table 3, entry 1). In contrast, in the pres-
ence of an excess of methanol, this potential Lewis
base may trigger B-to-In transmetalation to generate
IndiumACHTUNGTRNEUNG
(III) hexamethyldisilazide[13] (0.1–10 mol%), dry tol-
uene (0.5–2M), dry methanol (20–300 mol%), the corre-
sponding ketone 1a–1s (0.4 mmol), and the corresponding
boronates 2 or 4 (1.1–1.5 equiv.) were added successively to
a flame-dried, 5-mL screw vial with a magnetic stirring bar
under argon. The reaction mixture was stirred at room tem-
perature until complete consumption of the corresponding
Table 4. Preliminary scope for crotylation with 4.[a]
1
ketone 1 occurred (monitored by H NMR analysis of ali-
quots of the reaction mixtures). The crude reaction mixture
was quenched with saturated aqueous Na2CO3 solution and
extracted with dichloromethane. The organic phases were
dried (Na2SO4), filtered, and concentrated under vacuum,
before purification using preparative thin-layer or flash
column chromatography (eluent=hexane!hexane/ethyl
acetate=2:1) to afford the corresponding tertiary homoallyl
alcohols 3a–3s, or 5a–5c, and 5h.
Acknowledgements
[a]
Isolated yields of a-adducts 5a–c and 5h after purification
on silica gel (PTLC).
This work was partially supported by a Grant-in-Aid for Sci-
entific Research from the Japan Society for the Promotion of
Science (JSPS), and the Global COE Program (Chemistry
Innovation through Cooperation of Science and Engineering)
of the University of Tokyo, Japan.
[b]
Reaction conditions:
4
(1.5 equiv.), InACTHNGUTRENNU(G III)ACHTGNUTREN(NNUG hmds)3
(5 mol%), MeOH (300 mol%), toluene (1–2M), room
temperature, 12 h.
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Catalytic Use of a Soluble OrganoindiumACHTNUTRGNEUNG(III) Species for Allylation and Crotylation of Ketones
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of
In
G
(hmds)3
as
a
soluble
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Goetze, U. Wannagat, H. J. Wismar, J. Organomet.
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In
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[16] Indeed, [In(III)
In(III)ACTHNURTGENNG(U hmds)3 through alcoholysis with tert-butyl alco-
ACHUTGTNERNNUG(III)ACHTUNTGREN(NUNG hmds)3 catalysis, under the present conditions,
A
E
is
accessible
from
R
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It should be noted that the same alcoholysis reaction
using InACTHNURTGNENG(U III)Cl3 does not proceed with complete con-
version, resulting in mixed In
ACHTUNGTREN(NUNG III) compounds (see
ref.[13b]).
[17] A reviewer suggested that an acyclic transition state
may be possible to give a syn-product. We cannot deny
this possibility at this moment.
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