A qualitative assessment of the accelerating ability of
MAO vs water can be gained from the lower yields of the
methylated products obtained after 12 h at -20 °C (Table
Table 2. MAO-Accelerated Methylalumination of R-Olefins14
2
, entries 1 and 3 vs Scheme 3 and Table 1, entry 1). These
shortcomings could be addressed by increasing the reaction
time to 24 h (entry 2) or by raising the temperature to 0 °C
(
entry 4). Furthermore, subjecting 1-octene to the MAO-
T
yielda
(%)
ee
accelerated carboalumination conditions cleanly led to the
desired product in a yield of 78% after 24 h at -20 °C, with
little or none of the undesired side products that were
observed in the water-accelerated reaction (entry 5). Although
the methylalumination proceeds at a slower rate, there are
two main advantages in using MAO vs water: slightly higher
ee’s appear to be achievable for alkyl-substituted alkenes
under the MAO-accelerated conditions, and the addition of
MAO to trimethylaluminum is not exothermic and poses less
of a safety hazard upon scale-up.
entry
(°C)
product, R
(%)
1
2
3
4
5
6
-20
-20
-20
0
-20
-20
4, TBDPSO(CH2)2
4, TBDPSO(CH2)2
5, TBDPSO(CH2)4
5, TBDPSO(CH2)4
6, CH3(CH2)5
46
88b
50
83
78b
82b
79c
80c
82c
81c
81d
74d
8, c-C6H11
a
Isolated yields. b Yield obtained after 24 h. Determined by chiral
HPLC (Chiralcel OD). Determined by Mosher ester analysis ( H NMR).
c
d
1
A more quantitative assessment of the rate difference
between water and MAO was obtained for the methyl-
alumination of styrene at 0 °C. Monitoring the appearance
of 2-phenyl-propane (obtained after quenching the reaction
mixture with 1 N HCl) by GC revealed that under the water-
accelerated conditions the reaction was 85% complete after
8 h (Figure 1). Under the MAO-accelerated conditions,
The mechanistic role of water in the Zr-catalyzed methy-
lalumination remains unclear. The results shown in Table 1
were obtained by the addition of 1 equiv of water to a
solution containing 2 and trimethylaluminum, but we found
that the order of addition is not crucial and that adding 2 to
a premixed solution of water and trimethylaluminum leads
to similar results.10 An obvious candidate for the rate
acceleration of cationic processes is MAO (methylalumin-
11
oxane). The role that MAO plays in the activation of Cp
2
-
ZrCl in Ziegler-Natta-type polymerizations has been well
2
12
established, and it seems quite reasonable that the addition
of water to a solution of trimethylaluminum could lead to
the in situ formation of MAO. Although we ruled out the
formation of MAO in our original report concerning the
6
water-accelerated carboalumination of terminal alkynes, we
reinvestigated the use of MAO as a potential substitute for
water in the present reaction. Under otherwise identical
reaction conditions, the addition of 1.2 equiv of commercially
13
available MAO also resulted in a significant rate enhance-
ment of the methylalumination of 3, providing the desired
chiral alcohol 4 in 46% yield and 79% ee (Table 2, entry
1
4
1).
(
10) Alkene 3 was methylated under otherwise identical conditions (-20
C, 12 h) in 79% yield and in 80% ee.
11) (a) Sinn, H.; Kaminsky, W. AdV. Organomet. Chem. 1980, 18, 99.
b) Pasynkiewicz, S. Polyhedron 1990, 9, 429.
12) Brintzinger, H. H.; Fischer, D.; M u¨ lhaupt, R.; Rieger, B.; Waymouth,
R. M. Angew. Chem., Int. Ed. Engl. 1995, 34, 1143.
13) Obtained from Aldrich as a 10% solution in toluene. Toluene was
evaporated in vacuo before use and replaced with CH2Cl2.
14) Typical Procedure. A solution of 0.036 g (0.054 mmol) of 2 in 4
°
Figure 1. Kinetic analysis of the Zr-catalyzed methylalumination
of styrene using no additive, 1.2 equiv of MAO, and 1.0 equiv of
water, respectively. Reactions were performed at 0 °C using 4-5
(
(
(
3
equiv of Me Al and 5 mol % of 2, and data were obtained by GC
(
analysis of quenched samples with dodecane as internal standard.
The concentration of styrene was kept constant at 0.17 M.
(
mL of CH2Cl2 was added to a solution containing 0.324 g (4.49 mmol) of
trimethylaluminum in 1 mL of CH2Cl2, followed by the addition of 1.2
mL of a 10% (by weight) solution of MAO in CH2Cl2. The resulting dark
purple homogeneous solution was cooled to 0 °C, and then 0.350 g (1.04
mmol) of 1-(tert-butyl-diphenylsilanyloxy)-5-hexene was added neat. The
reaction mixture was kept at 0 °C for 12 h before air was vigorously bubbled
through the reaction mixture until all volatiles were evaporated. The slurry
was extracted with CH2Cl2. The organic layer was washed with a 2 N NaOH
solution and brine, dried (MgSO4), filtered, and chromatographed on SiO2
however, only about 20% of the methylated product was
detected after this time. In contrast to the use of water or
MAO as an additive, no product could be detected in the
absence of either of these additives (i.e., the original
(
EtOAc/hexanes, 1:4) to yield 0.318 g (0.859 mmol, 83%) of (2R)-6-(tert-
butyl-diphenylsilanyloxy)-2-methyl-hexan-1-ol (5) in 81% ee as a colorless
oil. The enantiomeric excess was determined by chiral HPLC on a Chiralcel
OD column (1% i-PrOH/hexane): [R]D +3.7 (c 1.4, CHCl3); IR (neat) 3345,
3.68 (t, 2 H, J ) 6.3 Hz), 3.50 (dd, 1 H, J ) 10.5, 5.8 Hz), 3.41 (dd, 1 H,
J ) 10.4, 6.5 Hz), 1.60-1.55 (m, 3 H), 1.45-1.35 (m, 4 H), 1.08-1.03
13
(m, 10 H), 0.92 (d, 3 H, J ) 6.6 Hz); C NMR (75 MHz, CDCl3) δ 135.8,
134.3, 129.7, 127.8, 68.6, 64.0, 35.9, 33.0 (2×), 27.1, 23.3, 19.4, 16.7;
HRMS (EI) calcd for C19H25O2Si (M - C4H9) 313.1624, found 313.1626.
-
1
3
071, 3049, 2931, 2858, 1472, 1462, 1428, 1389, 1111, 1044, 701 cm ;
1
H NMR (300 MHz, CDCl3) δ 7.70-7.67 (m, 4 H), 7.44-7.37 (m, 6 H),
Org. Lett., Vol. 2, No. 12, 2000
1715