Organic Letters
Letter
b
asymmetric reactions, chiral ligands L6−L8 failed to produce
the desired adduct (entries 10−12, respectively).
The scope of the reaction for various 3,4-dihydroisoquino-
linium tetraarylborates was then explored (Scheme 2). The
Scheme 3. Substrate Scope (II)
e
Scheme 2. Substrate Scope (I)
a
b
c
d
a
b
On a 2 mmol (1.14 g) scale. At 80 °C. At 120 °C. Using chiral
At 80 °C. Reaction conditions: 0.2 mmol of 2-BPh4 in dioxane (1.0
e
diene ligand L1. Reaction conditions: 0.2 mmol of 2-BAr4 in dioxane
(1.0 mL), [RhCl(C2H4)2]2 (1.5 mol %), L5 (3.6 mol %), stirred at
100 °C.
mL), [RhCl(C2H4)2]2 (1.5 mol %), and L5 (3.6 mol %), stirred at
100 °C.
afford adducts (3fa−3ha) in 84−95% yields with 70−90% ee.
Asymmetric phenylation with substrates containing substituted
aromatic rings, regardless of whether they contained alkyl,
electron-withdrawing, or electron-releasing substituents, of-
fered the desired adducts (3ia−3oa) in 64−94% yields with
85−97% ee. 3,4-Dihydroisoquinolinium salts with extended π-
conjugation or an analogue derived from 9-benzyl β-carboline
were also applicable to this enantioselective reaction, furnish-
ing 3pa in 53% yield with 91% ee and 3qa in 77% yield and
88% ee. The newly formed stereogenic center was unequiv-
ocally determined by a single-crystal X-ray crystallography
analysis of 3pa to possess an R configuration.
Although various 3,4-dihydroisoquinolinium tetraarylborates
are applicable, a further investigation of the addition reaction
of the 1-methyl-3,4-dihydroisoquinolinium analogue, 4-BPh4,
under the optimized reaction conditions, failed to furnish the
adduct bearing a quaternary stereogenic center (Scheme 4, eq
1). A diminishing asymmetric induction was observed in the
case of the reaction with the isoquinolinium substrate 5-BPh4,
providing 3ba, after a subsequent reduction, in a combined
75% yield with 55% ee. This outcome suggests the 3,4-
dihydroisoquinolinium ions are preferable substrates in this
asymmetric transformation (eq 2). A limitation was found in
the case of a tetra-heteroarylborate-containing substrate 2n-
B(2-furyl)4, which afforded the desired adduct 3nb in 46%
yield with 23% ee (eq 3). While the use of PhBF3K gave no
desired adduct (Table 1, entry 2), 2a-Br underwent
alkenylation with potassium octenyltrifluoroborate to afford
product 3ah in a 47% yield, but with no stereoselectivity (eq
enantioselective reactions of N-PMB 3,4-dihydroisoquinoli-
niums harboring diverse tetraarylborates afforded the corre-
sponding adducts (3aa−3ag) in 21−85% yields with 80−94%
ee. Notably, the reaction temperature was found to be a key
factor in influencing the reactivity and enantioselectivity of the
reaction. For the substrate containing tetra-4-MeO-phenyl
borate, adjusting the reaction temperature to 80 °C is
necessary for the corresponding product 3ae to be produced
in 81% ee, compared to the observed 67% ee at 100 °C,
suggesting that the use of a lower reaction temperature resulted
in a satisfactory ee for a prenucleophile containing a para-
electron-releasing aryl group. On the contrary, the reaction of
the tetraarylborate substrate harboring 4-Cl-phenyl substitu-
ents required a 120 °C reaction temperature to allow the
production of 3af in an optimal 39% yield. In addition, an
enhanced 80% ee of 3ag was observed when the reaction was
carried out in the presence of the Rh(I)/L1 catalyst for a
bulkier 2-naphthyl nucleophile as opposed to the value of 40%
ee when using L5. Asymmetric reactions with substrates
bearing various N substituents provided the corresponding
products (3ba16−3ea) in 30−90% yields along with 77−97%
ee. Conducting this asymmetric reaction on a larger scale (2.0
mmol), under optimal reaction conditions, furnished 3aa in
70% yield without the erosion of the high enantioselectivity.
Further investigations focused on substrates with varying
3,4-dihydroisoquinolinium motifs were carried out (Scheme
3). Substrates, bearing substituents on the N-containing
heterocyclic ring core, underwent phenylation smoothly to
1143
Org. Lett. 2021, 23, 1141−1146