Communications
Table 3: Effects of catalysts 3 and 4 on the functionalization of a p-allyl
palladium acetate dimer.[a]
Scheme 2. Streamlined generation ofchiral allylic acetates. CDI =1,1’-
carbonyldiimidazole.
Yield [%][c]
B:L
ee [%][d]
[b]
Entry
LA
krel
1
2
–
1.0
9.7
–
20
85
0
>20:1
5.2:1
–
–
55
–
(R,R)-3
(R,R)-3
(R,R)-4
thylbenzoquinone gave only a trace amount of product in the
catalytic reaction (Table 1, entry 8).
3[e]
4
3.8
41
2.2:1
29
We envisioned three mechanistic scenarios (Scheme 3)
that are likely to effect the observed asymmetric induction
[a] Mock catalytic conditions; EtOAc (0.2m), AcOH (11 equiv), BQ
(20 equiv), RT, (molarity and equivalents are relative to Pd). [b] Rate and
selectivity determined by GC analysis and was compared to a standard
curve using nitrobenzene as an internal standard (see the Supporting
Information). [c] Determined by GC analysis on a chiral stationary phase.
[d] The ee values were determined by GC analysis with a chiral b-
cyclodextrin stationary phase. [e] No BQ added.
À
during the C O bond-forming step: I: coordination of
Scheme 3. Proposed modes ofaction of r chromium Lewis acid: I:
reductive elimination ofacetate by a [L*Cr(BQ)]-activated p-allyl
palladium complex; II: delivery ofan acetate group rfom [L*Cr(OAc)]
to [(p-allyl)Pd(BQ)L] complex; III: delivery ofan acetate group rfom
[L*Cr(OAc)] to an activated L*Cr(BQ)–Pd(p-allyl). L=ligand, L*=chiral
ligand.
are most consistent with a 3·BQ-promoted functionalization
(Scheme 3, scenario I). However, at this time we cannot rule
out a dual activation mechanism in which 4 delivers the
acetate nucleophile to a [(p-allyl)Pd(BQ)·3] electrophilic
intermediate (Scheme 3, scenario III).
In conclusion, we have reported a heterobimetallic PdII/
bis(sulfoxide)/CrIII(salen) system for the asymmetric allylic
[(salen)CrIIIF] (3) to BQ to promote and control the facial
selectivity in the reductive elimination of acetate from a [(p-
allyl)Pd(BQ)OAc] intermediate, II: delivery of an acetate
group to a [(p-allyl)Pd(BQ)L] intermediate from [(salen)-
CrIIIOAc] (4), or III: activation of a [(p-allyl)Pd(BQ)]
intermediate by [(salen)CrIIIF] (3) with a concurrent delivery
of acetate from [(salen)CrIIIOAc] (4).[10,13,14] To test these
hypotheses, reductive elimination from the synthetic p-allyl
palladium acetate dimer 6 was evaluated in terms of reaction
rates and selectivities. This study was carried out under
conditions that mimic the reaction of a monomeric p-allyl
palladium intermediate during one catalytic cycle (see the
Supporting Information). As hypothesized, the addition of
Lewis acid co-catalyst [(salen)CrIIIF] (3) led to a 10-fold
increase in the rate of functionalization relative to reaction
conditions that were otherwise identical but lacked 3 (Table 3,
entry 1 vs 2). Moreover, the branched allylic acetate was
furnished with comparable enantio- and regioselectivities to
those obtained under catalytic conditions (Table 3, entry 2 vs
Table 1, entry 6). As noted above, functionalization does not
occur with 3 in the absence of BQ (Table 3, entry 3).
C H oxidation of terminal olefins that proceeds with the
À
highest levels of enantioselectivity reported to date.[16] These
materials can be further enantioenriched through enzymatic
resolution to rapidly furnish optically pure building blocks in
high yields. To the best of our knowledge, this represents the
first report of the interaction of a chiral Lewis acid co-catalyst
with an organometallic intermediate that influences the
stereochemical outcome of a catalytic process. We anticipate
that this novel strategy will find widespread use in other
electrophilic, oxidative transition-metal-catalyzed processes
that are not amenable to asymmetric induction by using
conventional chiral ligands.
Experimental Section
General procedure for branched asymmetric allylic acetoxylation
(Table 3): A vial (2 mL, borosilicate) was charged with the substrate
(1.0 mmol), AcOH (1.1 equiv, 63 mL), and EtOAc (200 mL). The
liquid was then transferred to a vial (8 mL, borosilicate) containing
1,2-bis(phenylsulfinyl)ethanepalladium(II) acetate (1; 10 mol%,
0.10 mmol,
50 mg)
(1R,2R)-(À)-[1,2-cyclohexanediamino-N,N’-
bis(3,5-di-tert-butylsalicylidene)]chromium(III) fluorine (R,R)-3;
10 mol%, 0.10 mmol, 61.6 mg), 1,4-benzoquinone (2 equiv,
2.0 mmol, 216 mg), activated molecular sieves (4 bead; ca.
30 mg), and a teflon stir bar. After carefully stirring the reaction
mixture for 48 h at room temperature, the mixture was diluted with
EtOAc (3 mL), transferred into a separatory funnel, and diluted with
hexanes (200 mL). The organic layer was washed with saturated aq
NaHSO3 (1 50 mL) and 5% aq K2CO3 (2 50 mL). Caution: CO2 is
evolved when the aqueous solutions are combined. The combined
aqueous layers were back-extracted with hexanes (100 mL). The
combined organic layers were dried (MgSO4), filtered, and concen-
trated in vacuo. The resulting oil was redissolved in hexanes (50 mL)
To evaluate mechanistic scenario II, which invokes coun-
terion exchange to give [(salen)CrIIIOAc] (4; Scheme 3), we
independently synthesized 4 and examined its reactivity
under both catalytic and stoichiometric conditions. Enantio-
and regioselectivity as well as conversion are significantly
diminished by using 4 relative to 3 under both catalytic and
stoichiometric reaction conditions (Table 1, entry 7 vs 6,
Table 3, entry 4 vs 2).[15] These results are inconsistent with
asymmetric induction arising exclusively through the delivery
of an acetate group by 4 (Scheme 3, scenario II), while they
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2008, 47, 6448 –6451