Scandium-catalyzed regio- and stereospecific methylalumination of silyloxy/alkoxy-substituted alkynes and alkenes

Article abstract of DOI:10.1021/ja909126k

(Chemical Equation Presented) Various alkynes and alkenes having a tethered ether group undergo methylalumination reactions with unprecedented regio- and stereoselectivity in the presence of a cationic half-sandwich alkylscandium species as a catalyst. The oxygen atom of the ether group plays an important role in controlling the selectivity, possibly by coordinating to the metal center. Even when a bulky tert-butyl(diphenyl)silyloxy group is used as the tether group, there is no loss of selectivity.

Full text of DOI:10.1021/ja909126k

Published on Web 12/02/2009
Scandium-Catalyzed Regio- and Stereospecific Methylalumination of Silyloxy/
Alkoxy-Substituted Alkynes and Alkenes
Masanori Takimoto, Saori Usami, and Zhaomin Hou*
Organometallic Chemistry Laboratory, RIKEN AdVanced Science Institute, 2-1 Hirosawa,
Wako, Saitama 351-0198, Japan
Received October 27, 2009; E-mail: houz@riken.jp
Carbometalation, particularly methylalumination, of alkynes is
one of the most efficient methods for the synthesis of polysubstituted
alkenes, especially those with branching methyl groups (an
important class of structural units that are found in many biologi-
cally active natural compounds).1,2 Similarly, the methylalumination
of alkenes is also of considerable importance in synthetic organic
chemistry.3,4 The catalysts reported to date for these reactions have
been based mainly on group-4 metal complexes.2,4 In contrast, the
use of rare-earth (group 3 and lanthanide) metal-based catalysts
for the carbometalation of alkynes or alkenes has not been reported
previously. Although group-4 metal catalysts are useful, they have
limitations. The search for new catalysts for the carbometalation
of alkynes and alkenes is of obvious interest and importance.
4b quantitatively in 25 h at room temperature. In these reactions,
the methyl group was introduced to the alkyne carbon distal from
the tethered silyl ether. The nuclear Overhauser effect (NOE)
experiment showed that the double bond in the product 4b has a Z
configuration. Treatment of the reaction mixture with DCl/D2O
afforded deuterated (Z)-4b-d in 98% yield (>98% D content). These
results indicate that Me3Al probably undergoes syn addition to the
alkyne moiety to give (Z)-3b as an intermediate. Neither the neutral
dialkyl complex (2a or 2b) nor the activator (A) showed any
catalytic activity when used alone, suggesting that a cationic
scandium alkyl species is essential for this reaction.
Recently, cationic rare-earth metal alkyl complexes have emerged
as a novel class of catalysts for olefin polymerization.5,6 In contrast,
their potential as catalysts in organic synthesis remains almost
unexplored.7 We report here that the cationic half-sandwich
alkylscandium complexes generated from dialkyl precursors such
as (C5Me4R)Sc(CH2C6H4NMe2-o)2 (R ) Me, SiMe3)6c can serve
as excellent catalysts for the methylalumination of alkynes and
alkenes, particularly those having an ether tether group, to afford
the corresponding methylalumination products with unprecedented
regio- and stereoselectivity.
Various internal alkynes having an ether tether group could be
used in the present reaction. Some representative results are
summarized in Table 1. Generally, in the reactions of phenyl- or
alkyl-substituted alkynes such as 1c-g, the methyl group was
introduced to the Ct C carbon atom distal from the ether group in
a syn fashion to give exclusively the corresponding Z alkenes in
high yields after hydrolysis (Table 1, entries 1-5).8,9 In contrast,
methylalumination of trimethylsilyl (TMS)-substituted alkynes such
as 1h-l took place in an anti-selective manner with introduction
of the methyl group to the carbon atom proximal to the tethered
ether group (Table 1, entries 6-10).10,11 Under similar conditions,
the Zr-catalyzed reactions were found to show much lower activity
and lower selectivity. In a comparison experiment, the methylalu-
mination of 1g catalyzed by Cp2ZrCl2 (a representative Zr catalyst)
yielded a mixture of the two regioisomers in a much lower yield
(<10%). The use of Wipf’s improved procedure12 led to a better
yield (75%) but no regioselectivity (∼1:1).
We first examined the methylalumination of 1,4-diphenylbut-1-
yne (1a) using the cationic scandium species prepared in situ by
the reaction of bis(aminobenzyl)scandium complex 2a or 2b with
[Ph3C][B(C6F5)4] (A).6c However, this reaction showed poor
selectivity, yielding an inseparable mixture of two regioisomers (∼2:
1) in a low yield (∼20%). Surprisingly to us, when an internal
alkyne having a tethered siloxy group, such as 1b, was reacted with
Me3Al in the presence of 2a/A (5 mol %), the reaction proceeded
in a regio- and stereoselective manner to give exclusively the Z
isomer of the hydromethylation product 4b after hydrolysis (Scheme
1). The C5Me5-ligated complex 2b showed a higher activity than
the C5Me4SiMe3 analogue 2a under the same conditions, giving
Scheme 1. Sc-Catalyzed Carboalumination of 1ba
In the present Sc-catalyzed methylaluminations of alkynes, the
resulting alkenylalane intermediates could be trapped in “one pot”
by various electrophiles. In contrast with the conventional Zr-
catalyzed reactions,13 removal of the solvent or unreacted Me3Al
was not required for the subsequent cross-coupling reactions because
the Sc-catalyzed methylalumination reactions could be carried out
in an inert solvent (toluene) with only a slight excess of Me3Al
(∼1.1 equiv). Thus, treatment of the alkenylalane generated from
1g with paraformaldehyde, allyl bromide, and iodobenzene gave
the corresponding syn adducts 6a, 6b, and 6c with introduction of
the electrophile at the carbon atom proximal to the tethered
benzyloxy group (Table 1, entries 11-13). Analogously, the
alkenylalane prepared from 1h reacted with iodine, paraformalde-
a TBDPS ) tert-BuPh2Si. b Isolated yield. c The reaction mixture was
treated with 20% DCl/D2O.
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18266 J. AM. CHEM. SOC. 2009, 131, 18266–18268
10.1021/ja909126k  2009 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Sc-Catalyzed Methylalumination of Alkenesa
Table 1. Sc-Catalyzed Methylalumination of Alkynesa
a Methylaluminations were carried out using 1.5 equiv of Me3Al, 5
mol % Sc precatalyst, and 5 mol % A. Oxidative workup was carried
out at
0
°C. For details, see the Supporting Information. b The
diastereomeric ratio (dr) of 9b was 1:1 (as determined by 1H NMR
analysis). c dr ) ∼1.6:1. d dr ) ∼1:1.4.
homoallylic alcohol derivative 8a reacted smoothly and regiose-
lectively with Me3Al in the presence of 2a/A (5 mol %), affording
the secondary alcohol 9a in 93% isolated yield after oxidation of
the resulting alkylalane species (Table 2, entry 1). It is noteworthy
that the AlMe2 unit was introduced at the internal carbon atom in
this reaction. This is in sharp contrast with what was observed in
the Zr-catalyzed methylalumination of 8a, in which the aluminum
atom was introduced at the terminal carbon.14 The methylalumi-
nations of secondary homoallylic ether 8b and internal alkenes 8c
and 8d also proceeded similarly (Table 2, entries 2-5).15 In each
case, the AlMe2 unit was introduced at the CdC carbon atom
proximal to the ether group to give the corresponding secondary
alcohol in high yield after oxidation.
Although the mechanistic details of the present Sc-catalyzed
reactions are yet not clear, it seems certain that the tethered oxygen
atom in the alkyne or alkene plays a crucially important role. A
likely mechanism for the reaction of alkyl- or phenyl-substituted
alkynes is proposed in Scheme 2. In the presence of Me3Al and
[Ph3C][B(C6F5)4], the bis(alkyl)scandium complex 2b may undergo
alkyl ligand exchange and alkyl abstraction to afford cationic
heteronuclear Sc/Al complex 10.16 Coordination of an ether-tethered
alkyne to the metal center may take place through both the oxygen
atom and the Ct C unit to give the intermediary complex 11.
Subsequent migratory addition of a methyl group to the Ct C unit
in 11 would afford vinylscandium intermediate 12. Intramolecular
transmetalation in 12 should give the syn methylalumination product
13, which upon reaction with AlMe3 could yield alkenylalane syn-
14 and regenerate 10. The regioselective methylalumination of
alkenes 8a-d (Table 2) could take place through a similar pathway.
In the case of TMS-substituted alkynes 1h-l (Table 1, entries
6-10), the reaction may take place similarly.10 However, the strong
electronic effect of the TMS substituent17 could direct the aluminum
a Methylaluminations were carried out using 1.1-1.5 equiv of Me3Al,
5 mol % Sc precatalyst, and 5 mol % A. For details, see the Supporting
Information. b TBDMS ) tert-BuMe2Si. c Using 1.1 equiv of BuLi.
d CuCl (30 mol %) catalyst. e ZnCl2 (1.1 equiv) + Pd(PPh3)4 (5 mol %)
catalyst.
hyde, and allyl bromide to afford the corresponding anti adducts
7a, 7b, and 7c with introduction of the electrophiles at the carbon
atom distal from the tethered siloxy group (Table 1, entries 14-16).
The usefulness of the present Sc-based catalyst system was
further demonstrated by the methylalumination of alkenes. The
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C O M M U N I C A T I O N S
Scheme 2. Possible Mechanism for the Reaction
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tion of the oxygen atom to the Al atom.19
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In summary, we have demonstrated that cationic alkylscandium
species such as that generated from the in situ reaction of 2a or 2b
with A can serve as a highly effective catalyst system for the regio-
and stereoselective carboalumination of internal akynes and alkenes
having an ether tether group. In most cases, the regio- and
stereoselectivity are unique and could not be achieved using
previously known catalysts. The resulting vinylalane species in the
carboalumination of alkynes can be easily transformed to the
corresponding tetrasubstituted alkenes through one-pot, stereospe-
cific coupling reactions with electrophiles. The oxidation of the
alkylalane species formed in the carboalumination of alkenes
selectively affords the corresponding secondary alcohols. Studies
of the use of the cationic rare-earth metal alkyls for other synthetic
organic reactions are in progress.
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(12) Wipf, P.; Lim, S. Angew. Chem., Int. Ed. Engl. 1993, 32, 1068.
(13) In the Zr-catalyzed carboalumination reactions, an excess amount of Me3Al
(∼3.0 equiv) and a chlorinated solvent are usually required, and therefore,
removal of the unreacted Me3Al and the reactive solvent is necessary when
the resulting alkenylaluminum species are subsequently submitted to
coupling reactions with electrophiles. For examples, see: (a) Okukado, N.;
Negishi, E. Tetrahedron Lett. 1978, 19, 2357. (b) Ireland, R. E.; Wipf, P.
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(15) The reaction of (Z)-8d or (E)-8d afforded 9d as a similar inseparable mixture
of two diastereomers. Oxidation of these alcohols gave the corresponding
ketone as the sole product in high yield, which shows that the methylalu-
mination proceeded in a regioselective manner (see the Supporting
Information). The lack of stereoselectivity may be due to the partial
involvement of a radical process in the oxidation reaction.
Acknowledgment. This work was partially supported by a
Grant-in-Aid for Young Scientists (B) (20790026) and a Grant-in-
Aid for Scientific Research (S) (21225004) from JSPS.
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Supporting Information Available: Experimental details and
compound characterization data. This material is available free of charge
via the Internet at http://pubs.acs.org.
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