Tris(trimethylsilylmethyl)alane: An aldehyde selective peterson methylenation reagent

Article abstract of DOI:10.1016/j.jorganchem.2004.02.009

Tris(trimethylsilylmethyl)alane (TTMA) is a rapid, efficient, and highly aldehyde-selective trimethylsilylmethylating reagent. A solid lithium halide complex of the reagent, TTMA·3LiBr (TTMAs), is particularly effective in this transformation to the Peterson alcohol intermediate.

Full text of DOI:10.1016/j.jorganchem.2004.02.009

Journal of Organometallic Chemistry 689 (2004) 1856–1859
www.elsevier.com/locate/jorganchem
Tris(trimethylsilylmethyl)alane: an aldehyde selective peterson
methylenation reagent
*
Vahak Abedi, Merle A. Battiste
Department of Chemistry, University of Florida, Gainesville, FL 32611, USA
Received 14 October 2003; accepted 6 February 2004
Abstract
Tris(trimethylsilylmethyl)alane (TTMA) is a rapid, efficient, and highly aldehyde-selective trimethylsilylmethylating reagent. A
solid lithium halide complex of the reagent, TTMA Æ 3LiBr (TTMAs), is particularly effective in this transformation to the Peterson
alcohol intermediate.
Ó 2004 Published by Elsevier B.V.
Keywords: Tris(trimethylsilylmethyl)alane; Aldehyde vs. ketone selectivity; Peterson methylenation
1. Introduction
2. Results and discussion
The list of organometallic reagents applicable to or-
ganic synthesis continues to expand; however, the stated
goal of reaction specificity for an indicated functional
group, i.e. carbonyl, nitrile, epoxide, etc., remains elu-
sive with rare exceptions [1]. For example, there is only
one reported [2] example of a synthetically useful alde-
hyde selective Peterson methylenation reagent
(Me3MCH2TiCl3; M ¼ Si, Ge). We now report that
under proper conditions tris(trimethylsilylmethyl)alane
(TTMA) functions as a rapid and effective trim-
ethylsilylmethylating agent for aldehydes even in the
presence of the ketone moiety.
Trialkylalanes are chemoselective in their reactions
with carbonyl compounds [3]. In an effort to expand the
synthetic potential of triorganoalanes, we discovered
that the trimethylsilylmethyl (TMSCH2) group com-
petes poorly, if at all, with simple alkyls (methyl, ethyl)
for transfer from aluminium to a ketone carbonyl [4].
These results formed the basis for an investigation of the
known [5] TTMA as a chemoselective aldehyde reagent.
There are three reported preparations of TTMA [5,6].
For our purposes, we found the reaction of TMSCH2Li
with AlBr3 in hexane the most convenient (Eq. 1) [6a];
however, the separation of TTMA from the lithium salts
by distillation
Hexanes
3TMSCH2Li þ AlBr3 Reflux; 12h ðTMSCH2Þ þ 3LiBr ð1Þ
ƒ!
3
from the reaction flask proved time consuming and low
yielding. Furthermore, isolation of TTMA by cannula
filtration of the liquid phase was also unsuccessful,
leaving the alane apparently complexed with the LiBr
salt. Evaporation of the remaining volatiles from this
solid mixture led to the recovery of a white powder
[TTMAs ¼ (TMSCH2)3Al Æ 3LiBr], which proved to be
an unusually selective TMSCH2 transfer agent with al-
dehydes (Scheme 1).
The reactions of both the neat TTMA and its halide
bound salt (TTMAs) with selected aldehydes and ke-
tones were investigated and the results compiled in Ta-
bles 1 and 2, respectively. The results in Table 1 indicate
that in all instances the reactions of TTMAs are much
cleaner (fewer products) and higher yielding than in
TTMA alone. Still the carbonyl addition yields for both
reagents decreased when reacted with readily enolizable
carbonyls such as phenylacetaldehyde [7]. The lower
* Corresponding author. Tel./fax: +1-352-392-9131.
E-mail address: battiste@chem.ufl.edu (M.A. Battiste).
0022-328X/$ - see front matter Ó 2004 Published by Elsevier B.V.
doi:10.1016/j.jorganchem.2004.02.009

V. Abedi, M.A. Battiste / Journal of Organometallic Chemistry 689 (2004) 1856–1859
1857
Table 2
Reaction of (TMSCH2)3Al (TTMA) with selected ketones at room
temperature
Ketone
TTMAa
Conversion (%)
Addition
product
MPV
Red.
S.M.
Cyclohexanone
Acetophenone
1-Indanone
A
B
26b
39b
27
3
56
38
A
B
7b
8b(5)
4
2
71
59
–
–
93
36
B
9b(6)
2
9-Fluorenone
A
B
17b
43b
–
–
55
51
a A: Neat (TMSCH2)3Al, B: (TMSCH2)3Al Æ LiBr salt.
b Total percentage of addition products (including the elimination
products); S.M.: Starting material. Yields based on GC analysis,
tridecane used as internal standard. Hexane or hexane/CH2Cl2 used as
solvent; reactions quenched after 4 h.
Scheme 1.
yield observed with 4-methoxybenzaldehyde is appar-
ently the result of facile elimination of trimethylsilanol
from the addition product to form readily polymerizable
4-methoxystyrene. The major side products from these
reactions, which are most pronounced in reactions of the
neat TTMA, are the alcohols produced from the
Meerwein–Pondorff–Verely (MPV) reduction of the
starting aldehyde coupled with Oppenauer oxidation of
the trimethylsilylmethyl alcohol (Scheme 1). These
newly formed ketones have been observed to condense
readily with the starting aldehyde in some instances,
leading to a more complex product mixture. In reactions
involving the TTMAs these reduction–oxidation pro-
cesses are of minor significance [8].
The carbonyl selectivity of TTMA and TTMAs be-
comes evident upon examination of their reactivity with
ketones (Table 2) in contrast with aldehydes. In all
cases, the recovered starting ketone was the major
constituent in the product mixture. The sluggish reac-
tivity of TTMA (or TTMAs) with ketones is attributed
to: (a) the bulk of the reagent, which may hinder com-
plexation with the more sterically demanding ketones;
Table 1
Reaction of (TMSCH2)3Al (TTMA) with selected aldehydes at room temperature
Aldehyde
TTMAa
Conversion (%)
Addition product
MPV Red.
Cond.c
S.M.c
Benzaldehyde
A
B
53b(21)
100b
27
–
–
–
–
–
4-Toluldehyde
A
B
63b(21)
79b
35
19
4-Trifluoromethyl-benzaldehyde
4-Chlorobenzaldheyde
Anisaldehyde
–
–
–
–
–
–
–
–
B
61b
A
B
38b(20)
100b
10
–
–
–
31
–
A
B
46b(26)
35b(31)
33
2
4
6
10
–
Phenylacetaldehyde
Heptanal
A
B
41b
38b
–
–
2
15
5
27
A
B
57b(17)
83b(3)
24
4
–
–
–
2
a A: Neat (TMSCH2)3Al, B: (TMSCH2)3Al Æ LiBr salt.
b Total percentage of addition products (including the elimination products).
c Cond.: Total of condensation products. S.M.: Starting material. Yields based on GC analysis, tridecane used as internal standard. Hexane or
hexane/CH2Cl2 used as solvent; reactions quenched after 4 h.

1858
V. Abedi, M.A. Battiste / Journal of Organometallic Chemistry 689 (2004) 1856–1859
(b) steric crowding in the transition state for transfer
of the bulky TMSCH2 group from Al to carbon. One
should note again, that the LiBr complex appears to
be the more reactive reagent with ketones as well as
aldehydes.
4. Experimental
Distilled TTMA was obtained by the previously de-
scribed procedure [6a]. For TTMAs (LiBr salt) similar
steps were followed as for neat TTMA up to the distil-
lation step; at this point the solids were filtered using a
cannula filter and washed with hexane. The solid pow-
der was then dried under vacuum (0.01 mm Hg) and
stored in the dry box. The IR (KBr) spectrum of the
powder was essentially indentical to that reported for
Although the data in Tables 1 and 2 provide ade-
quate, if indirect evidence for the carbonyl selectivity of
TTMA, a more direct and convincing measure of this
selectivity is available when both aldehyde and ketone
carbonyl functionalities are contained within the same
substrate. Hence, the selectivity of TTMA was put to the
more challenging test of reaction with keto-aldehydes 9-
oxofluorenyl-4-carboxaldehyde (1) and 3-acetyl-2,2-
dimethylcyclobutane-carboxaldehyde (2) [9] (Scheme 2).
The reaction of TTMAs with 1 in hexane/methylene
chloride solution (ca. 20 min) at room temperature
yielded 94% of the aldehyde addition product 3. Under
similar conditions 2 yielded 76% of the aldehyde addi-
tion product 4 (ca. 15 min).
1
TTMA [6], while the H NMR (THF-d8) spectrum re-
vealed a broadened complex multipet centered at 0.00
ppm. The mass spectrum (70 eV) of the powder showed
a base peak at m=z 73 (Me3Si) and a parent peak at 295
[(Me3SiCH2)3AlLi]. As required, the reagent (TTMA or
TTMAs) was weighed into the appropriate flask (in the
dry box) before each reaction.
4.1. Typical procedure for reaction of TTMA or TTMAs
with aldehydes
The high selectivity of TTMAs with 1 might have
been expected, for steric reasons; however, in 2 the ke-
tone and aldehyde moieties are sterically more compa-
rable, and yet a 19 to 1 aldehyde selectivity is observed.
All glassware and syringes were dried in the oven over
night and all reactions were carried out under an Ar
atmosphere. In the dry box, 2.5 mmol of TTMA or
TTMAs were weighed into a round bottom flask
equipped with a septum and a magnetic stirring bar.
Freshly distilled hexane (25 ml) was added and the
suspension (or solution) stirred for 15 min. A solution of
aldehyde (2.0 mmol) in 4 ml of hexane was added
dropwise to the cooled (0 °C) suspension (or solution) of
the reagent and then allowed to warm to room tem-
perature. After 4 h the reaction mixture was quenched
by addition of 1.0 M HCl (with cooling). The usual
workup afforded a yellow clear oil which was analyzed
by capillary GC. Note: appropriate amounts of CH2Cl2
were used to dissolve those carbonyl compounds which
3. Conclusions
The superiority of the LiBr salt of the TTMA
(TTMAs) compared to the neat liquid reagent is clear in
that: (a) it affords much higher yields; (b) it is more
stable when exposed to moisture and oxygen; (c) it is
easier to handle (powder) and can be stored for months.
When compared to other Peterson methylenation re-
agents [1,2,7], TTMAs is also advantageous since it re-
quires moderate temperatures (0–25 °C), shorter
reaction times, and a 1.3–1 ratio of reagent to aldehyde.
O
O
TTMAs
Hex. r.t.
20 min.
94%
H
OH
O
Me3Si
O
OH
H
O
TTMAs
O
Hex. r.t.
15 min.
Me3Si
76%
Scheme 2.

V. Abedi, M.A. Battiste / Journal of Organometallic Chemistry 689 (2004) 1856–1859
1859
were not completely soluble in hexane. All reactions
with aldehydes were complete within 30 min.
1: [from reduction of corresponding acid chloride
MS: m=z, (70 eV) 241 (0.3), 223(1), 199(2), 171(2), 117(21),
99(38), 75(48), 73(100): IR (neat): (OH) 3439, (C@O)
1710 cmꢀ1
.
1
(Aldrich)]: m.p. 173–175 °C; H NMR: (CDCl3) d 7.41
(td, JHz ¼ 7.2, 1.0; 1H), 7.48 (t, JHz ¼ 7.3: 1H), 7.56 (td,
JHz ¼ 7.5, 1.5; 1H), 7.73 (dm, JHz ¼ 7.27; 1H), 7.89 (dd,
JHz ¼ 7.2, 1.5; 1H), 7.98 (dd, JHz ¼ 7.4, 1.5; 1H), 8.33 (dt,
JHz ¼ 7.4, <0.5; 1H), 10.43 (s, 1H); 13C NMR: d 124.4,
126.7, 128.8, 129.1, 130.4, 132.5, 134.4, 135.4, 135.6,
137.5, 142.9, 144.8, 190.8, 192.3; HRMS: m=z (70 eV),
208 (100), 180 (88), 152 (40), 151 (46.0), 150 (32.5), 75
(21.0); calculated for C14H8O2 208.05243, found
Acknowledgements
We gratefully acknowledge financial support from the
Research Corporation in the form of a Research Op-
portunity Award to M.A.B.
208.05060; IR (KBr): (C@O) 1718, 1688 cmꢀ1
.
2: (from ozonization of a-pinene) [9]: 1H NMR:
(CDCl3) d 0.85 (s, 3H), 1,34 (s, 3H), 1.98 (q, JHz ¼ 7.64;
2H), 2.06 (s, 3H), overlapping peaks 2.25–2.54 (m, 3H),
2.93 (dd, JHz ¼ 9.76, 7.81; 1H), 9.75 (t, JHz ¼ 1.45; 1H);
13C NMR: d 17.50, 17.55, 22.7, 30.0, 35,6 43.2, 44.9,
54.2, 201.4, 207.4; GC/MS m=z (CI, methane), 169 (14),
151 (72), 127 (14), 107 (39), 99 (58), 71 (100); IR (neat):
References
[1] For a comprehensive survey of reagents and conditions related to
the title reactions see: S.H. Pine, Org. React. 43 (1993) 1;
D.J. Ager, Org. React. 38 (1988) 1.
[2] T. Kauffman, R. King, Tetrahedron Lett. 22 (1981) 5031.
[3] G. Bruno, The Use of Aluminum Alkyls in Organic Synthesis,
Ethyl Corporation, 1970;
G. Bruno, The Use of Aluminum Alkyls in Organic Synthesis
(Suppl. 1), Ethyl Corporation, 1973;
(C@O) 1724, 1705 cmꢀ1
.
1
3: m.p. 121–123 °C; H NMR: (CDCl3), d 0.00 [(ref.
Me3Si–) (s, 9H)], overlapping peaks 1.18: [(d, JHz ¼ 8.35;
1H), (d, JHz ¼ 6.29; 1H)], 2.01 (d, JHz ¼ 3.61; 1H), 5.34
(td, JHz ¼ 7.26, 3.54; 1H), 7.16 (t, JHz ¼ 7.62; 1H), 7.18
(t, JHz ¼ 7.84; 1H), 7.38 (td, JHz ¼ 7.59, 1.30; 1H), 7.44
(br d, JHz ¼ 7.18; 1H), 7.56 (br d, JHz ¼ 7.87; 1H), 7.61
(br d, JHz ¼ 7.76; 1H); 13C NMR: d )0.76, 26.2, 69.1,
123.1, 124.3, 124.8, 128.5, 129.1, 132.1, 134.0, 134.5,
134.7, 134.7, 143.3, 144.2, 194.2; HRMS: m=z (GC/EI,
70 eV), 296 (36), 281 (100), 267 (18), 209 (65), 206 (36),
178 (82), 162 (40), 75 (99), 73 (48) calculated for
C18H20O2Si, 296.1233, measured 296.123; IR (KBr):
(J.B. Honeycutt, The Use of Aluminum Alkyls in Organic Synthesis
(Suppl. 2), Ethyl Corporation, 1979;
T. Mole, E.A. Jeffery, Organoaluminum Compounds, Elsevier,
Amsterdam, 1972.
[4] V. Abedi, Ph.D. Dissertation, University of Florida, 1991.
[5] J.Z. Niathi, J.M. Ressner, J.D. Smith, J. Organomet. Chem. 70
(1974) 35.
[6] (a) O.T. Beachley Jr., C. Tessier-Youngs, Inorg. Chem. 21 (1982)
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(b) M.G. Saulnier, J.F. Kadow, M.M. Tun, D.M. Vyas, D.R.
Langley, J. Am. Chem. Soc. 111 (1989) 8320.
[7] The cerium (III) reagent of Johnson and Tait may be preferable in
the case of readily enolizable aldehydes: R. Johnson, B.D. Tait, J.
Org. Chem. 52 (1987) 281.
(OH) 3509, (C@O) 1608 cmꢀ1
.
[8] The enhanced reactivity of the TTMAs may be tentatively
attributed to several factors: (a) the observed higher stability of
the TTMAs towards exposure to oxygen and moisture which may
contribute to a reduction in reactivity of the reagent and lead to
undesired side products; (b) increased electrophiliciy of the
carbonyl group due to complexation of Liþ with the carbonyl
oxygen; and (c) the presence of the Brꢀ in the reaction mixture
appears to assist in breaking up alkylaluminum-oxide aggregates.
The latter effect should increase the reactivity of the alane as well as
counteract the reduction–oxidation processes which involve an
alkoxyaluminum-aldehyde complex (Scheme 1; path b).
[9] H.-D. Scharf, H. Kalkoff, J. Janus, Tetrahedron 35 (1979) 2513,
and references cited therein.
1
4: H NMR: (CDCl3), d 0.00 [(ref. Me3Si–), (s, 9H)],
overlapping peaks [0.78 (d, JHz ¼ 6.9), 0.81 (s), 0.82 (d,
JHz ¼ 6.2); total 5H], 1.25 (s, 3H), overlapping peaks
[1.30–1.56 (m), total 3H)], 1.75–1.98 (m, 2H), 2.00 (s, 3H),
2.02–2.14 (m, 1H), 2.79 (dd, JHz ¼ 8.88, 8.62; 1H), 3.70
(m, 1H); 13C NMR shows mixture of two isomers: d 0.00,
18.09(18.05), 23.93, 24.74, 27.86(29.16), 30.78(31.16),
39.70(39.37), 41.91(41.48), 44.23(43.91), 55.34(55.08),
68.63(70.02), 208.70(208.65); HRMS: m=z (GC/CI), cal-
culated for C14H28O2Si 256.1859, found 256.1885; GC/