Asymmetric Catalysis
FULL PAPER
1 mLminÀ1
, 254 nm): t1 =11.47, t2 =
12.78). [a]D (c=0.92 in CHCl3):
+22.98; 1H NMR (300 MHz, CDCl3):
d=7.37–7.20 (m, 5H), 6.11 (ddd, J=
19.8, 10.5, 9.3 Hz, 1H), 5.53 (dd, J=
9.5, 1.5 Hz, 1H), 5.38 (dd, J=18.7,
1.2 Hz, 1H), 4.55 (d, J=10.8 Hz, 1H),
4.29 (m, 2H), 1.70 (s, 3H), 1.67 (s,
3H), 1.46 ppm (s, 3H); 13C NMR
(75 MHz, CDCl3): d=132.0, 128.2,
123.5, 123.3, 123.1, 118.3, 101.1, 81.8,
66.1, 48.1, 24.8, 23.9, 17.0 ppm; IR
(film): n˜ =1741.5, 1379, 1290, 1204,
1069 cmÀ1
; elemental analysis calcd
(%) for C17H20O5 (304.34): C 67.09, H
6.62; found: C 66.91, H 6.47.
Representative procedure for addition
of 1,3-diketones to allene 11
3-(1-Benzyloxy-allyl)-3-furan-2-yl-
methyl-pentane-2,4-dione (16e): De-
gassed CH2Cl2 (0.7 mL) was added to
a mixture of ligand (R,R)-12 (8.85 mg,
Scheme 3. Mechanistic pathways in the hydropalladation of allene 11.
3.75 mol%), (allyl)2Pd2Cl2 (1.87 mg,
1.5 mol%) and PhCO2H (2.09 mg,
favored over complexes 24a,b due to p-basicity, sterically
the opposite is true. Thus, pathways a and b are expected to
compete leading to formation of both complexes 27 and 28.
Reductive elimination converts intermediates 27a and 28b
into product 29 and 27b and 28a into ent-29. Previous work
showed that, under the catalytic system employed herein, ef-
ficient p-facial discrimination occurs in some processes.[26,27]
Selection of either 25a or 25b could involve diastereoselec-
tion in the formation of either complexes 23 or lowering of
the energy of one of the involved transition states. The fact
that the product obtained corresponds to ent-29 when using
the R,R ligand requires that 27b and/or 28a be the reactive
intermediates in this ligand-controlled reaction. Neverthe-
less, considering that our results suggests that high stereose-
lectivities depend on efficient equilibration of the p-allyl–Pd
intermediate, such initial p-facial diastereoselectivity could
explain the substantial formation of minor enantiomer 29 in
some reactions. Furthermore, structural studies[6a,18] do not
support the possibility of syn and anti intermediates 27b and
28a, respectively, converging to the same product ent-29.
The allyl systems thereof would not fit equally well in the
chiral catalyst pocket.
5.0 mol%), and the resulting mixture was allowed to stir at RT for
ꢀ30 min under inert atmosphere. Then, neat 3-furylmethyl-2,4-pentane-
dione, (15e; 61.6 mg, 57.0 mL, 0.342 mmol), Et3N (0.86 mg, 2.5 mol%;
added as a freshly prepared solution in degassed CH2Cl2), and neat
allene 11 (65 mg, 66.7 mL, 0.445 mmol), in this order, were added by sy-
ringe, and the resulting mixture was stirred for 15 h at RT. The reaction
mixture was then filtered through a short plug of silica gel and eluted
with EtOAc/petroleum ether (1:1). After evaporation of the volatiles, the
crude product was purified by flash chromatography to give compound
16e as a colorless oil (108 mg, 97%) with an ee=98% (HPLC: Daicel
OD-H, heptane/2-propanol (90:10), 254 nm; 1 mLminÀ1
; 13.76 min
(minor) 17.85 min (major)). [a]2D2:2 =+8.75 (c=1.12 in CHCl3); 1H NMR
(300 MHz, CDCl3): d=7.36–7.28 (m, 5H), 6.25 (m, 1H), 6.01 (d, J=
3.0 Hz, 1H), 5.59 (m, 1H), 5.47–5.41 (m, 3H), 4.62 (d, J=11.1 Hz, 1H),
4.45 (d, J=7.5 Hz, 1H), 4.33 (d, J=11.1 Hz, 1H), 3.28 (d, J=15.4 Hz,
1H), 3.08 (d, J=15.4 Hz; 1H), 2.21 (s, 3H), 2.09 ppm (s, 3H); 13C NMR
(75 MHz, CDCl3): d=207.5, 205.4, 150.3, 141.6, 137.5, 132.6, 128.3, 127.6,
127.4, 121.4, 110.5, 108.8, 81.7, 72.4, 70.9, 30.5, 30.3, 28.0 ppm; IR (neat):
n˜ =1699.1, 1421.5, 1355.4, 1193.4, 1146.1, 1068.4, 1010.9, 939.3, 735.9,
698.7 cmÀ1; elemental analysis calcd (%) for C20H22O4: C 73.60, H 6.79;
found:
326.1517.
C 73.72, H 6.70; HRMS (EI): m/z calcd: 326.1518; found:
Mosherꢀs ester 22a: A mixture of alcohol 21 (18.5 mg, 98.3 mmol) (S)-
MTPA chloride (15.0 mL, 80.3 mmol), and DMAP (12.0 mg, 98.2 mmol)
in CH2Cl2 (0.5 mL) was stirred at room temperature for 2 h ((S)-
MPTA=a-methoxy-a-(trifluoromethyl)phenylacetic acid; DMAP=4-di-
methylamino pyridine). Then, it was concentrated and purified by flash
chromatography to give ester 22a (24.9 mg, 77%). [a]D =+27.96 (c=1.0
in CH2Cl2); 1H NMR (500 MHz, CDCl3): d=7.59–7.58 (m, 2H), 7.42–
7.40 (m, 3H), 5.30 (dd, 1J=10 Hz, 2J=2.5 Hz, 1H), 3.69 (d, J=11.5 Hz,
1H), 3.60 (d, J=12 Hz, 1H), 3.56 (s, 3H), 3.45 (d, J=11.8 Hz, 1H), 3.37
(d, J=12 Hz, 1H), 1.73–1.69 (m, 1H), 1.64–1.59 (m, 1H), 1.38 (s, 3H),
1.35 (s, 3H), 0.93 (t, J=7.5 Hz, 3H), 0.92 ppm (s, 3H); 13C NMR
(125 MHz, CDCl3): d=166.2, 132.0, 129.7, 128.5, 127.5, 98.2, 79.9, 66.5,
66.4, 55.5, 37.3, 23.7, 22.6, 15.8, 11.1 ppm; IR (neat): n˜ =2977, 2940, 2877,
1746, 1451, 1393, 1374, 1257, 1207, 1189, 1166, 1121, 1085, 1017, 908, 826,
768, 713 cmÀ1; elemental analysis calcd (%) for C20H27O5F3: C 59.40, H
6.75; found: C 59.18, H 6.86.
Experimental Section
Representative procedure for addition of Meldrumꢀs acid derivatives 2 to
allene 11
5-(1-Benzyloxy-allyl)-2,2,5-trimethyl-[1,3]-dioxa-4,6-dione (13a):[13] In a
4 mL Minivert pressure vial, a mixture of [Pd(OTFA)2](6.7 mg), ligand
(R,R)-12 (17 mg) and methyl Meldrumꢀs acid 2a (316.3 mg, 2.0 mmol)
was evacuated and flushed with Ar three times and then diluted with
CH2Cl2 (4.5 mL). Then, a freshly prepared 1m solution of TFA in CH2Cl2
(20 mL) was added by syringe. After 30 min of stirring at RT, allene 11
(2.0 mmol) was added by syringe. After stirring overnight, the product
was purified by direct flash chromatography on silica gel (3:2 petroleum
ether/Et2O) to yield 13a[13] (527.7 mg, 87%) as a colorless oil, which sol-
idified upon standing, with an ee of 97%. Enantiomeric excess was deter-
mined by chiral HPLC (Chiralcel AD, heptane/2-propanol (99:1), flow:
Mosherꢀs ester 22b: The procedure was the same as the one employed in
the preparation of compound 22a, except for the use of (R)-MTPA chlo-
ride. The yield was 56% (83% based on recovered starting material).
[a]D =À10.96 (c=1.0 in CH2Cl2); 1H NMR (500 MHz, CDCl3): d=7.57–
7.55 (m, 2H), 7.42–7.41 (m, 3H), 5.26 (dd, 1J=10 Hz, 2J=2.5 Hz, 1H),
3.70 (d, J=12 Hz, 1H), 3.64 (d, J=12 Hz, 1H), 3.50 (s, 3H), 3.45 (d, J=
Chem. Eur. J. 2005, 11, 7075 – 7082
ꢁ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
7081