Organic Letters
Letter
amines, providing the desired products in good yields and high
enantioselectivities (3a−3n, 52%−96%, 90%−99% ee). We
noticed that biaryl-2-amines bearing electron-withdrawing
groups at the naphthyl ring is less reactive, but with little
influence on the enantiocontrol (3d vs 3a, 3b, 3c).
Substituents at the upper phenyl ring, no matter electron-
withdrawing or electron-donating, were well-tolerated (3e−3j,
62%−85%, 92%−99% ee). Biaryl-2-amines 1k and 1l, bearing
two substituents at the upper phenyl ring, were also compatible
to give the desired products in high ees (3k, 94% ee; 3l, 91%
ee). Notably, our catalytic system is also compatible with
biphenyl-2-amines, affording the corresponding allylation
products in good yields and high enantioselectivities (3m,
77%, 93% ee; 3n, 82%, 90% ee).
derivated methacrylates, bearing two possible reactive groups,
afforded the monoallylic products in acceptable yields and
excellent enantioselectivities (4o, 52%, 97% ee; 4p, 64%, 96%
ee). The absolute configuration of products was assigned by
analogy to previously observed stereoinduction.12f
To demonstrate the potential of this C−H allylation
protocol, gram-scale synthesis and further transformation
reactions were conducted (Scheme 3). The asymmetric C−
Scheme 3. Synthetic Applications
We next explored the scope of methacrylates (Table 3). The
reaction of 1a with alkyl methacrylates proceeded in good
a
Table 3. Scope of Methacrylates
H allylation of 1a with 2g on a 5 mmol scale under standard
conditions gave the 4g in 95% yield and 98% ee (1.85 g). The
reaction of 4g with isothiocyanatoarene gave thiourea 5g in
59% yield and retention of chirality (98% ee). Thioureas with
axially chirality play an important role in hydrogen-bond
organocatalysts.164g could also be protected by benzyl to give
6g without the loss of enantioselectivity (72%, 99% ee).
Triazenens exhibit excellent application prospects in prepara-
tive chemistry, which were widely used in pharmacology, total
synthesis, polymer technology, and the construction of novel
ring systems.17 The amine group was readily transferred to the
synthetically more useful triazene group in excellent 95% yield
and 99% ee after treating with nitrite ion under acidic
conditions and subsequent quenching with piperidine.
Medium-sized lactams are found in a wide range of natural
products and molecules of biological significance, we
successfully developed a novel strategy for direct synthesis of
axially chiral medium-sized lactam 8g in excellent enantiose-
lectivity by treating 4g with tBuOK in THF at room
temperature.
a
Reaction conditions: 1a (0.1 mmol), 2 (4.0 equiv), Pd(OAc)2 (10
mol %), Ag2SO4 (2 equiv), (S)-STRIP (10 mol %), Na2HPO4 (2
equiv) in toluene (1.0 mL) at 60 °C.
yields and enantioselectivities (4b−4e, 68%−85%, 95%−97%
ee). Surprisingly, dramatic erosion of enantioselectivity
occurred when using tert-butyl methacrylate as the coupling
part (4f, 65%, 82% ee). Meanwhile, reaction with benzyl
methacrylate (2g) and furfuryl methacrylate (2h) provided
satisfactory results (4g, 85%, 98% ee; 4h, 75%, >99% ee).
Methacrylates 2i and 2j also underwent the desired allylation
smoothly, affording the corresponding products in high
enantioselectivities (4i, 42%, 95% ee; 4j, 81%, 95% ee). This
asymmetric transformation was also suitable for 2-methox-
yethyl methacrylate and 2-ethoxyethyl methacrylate, providing
the corresponding allylation products in moderated yields and
excellent enantioselectivities (4k, 75%, 97% ee; 4l, 61%, 98%
ee). Phenyl methacrylate was subsequently tested and the
allylation product was obtained in moderated yield and
excellent enantioselectivity (4m, 69%, 95% ee). Besides,
carvacrol-derivated methacrylate was also suitable for this
transformation, giving the allylation product 4n in 63% yield
and 99% ee. Note that glycol-derivated and bisphenol A-
In conclusion, we reported the highly efficient synthesis of
axially chiral biaryl-2-amines via Pd(II)-catalyzed enantiose-
lective C−H allylation with methacrylates. Exclusive allylic
selectivity was achieved. This reaction provides an efficient
method for the modification of axially biaryl compounds,
because the amine group can be readily converted to synthetic
useful functional groups. Further investigations of this protocol
to expand to other types of biaryl compounds are ongoing.
ASSOCIATED CONTENT
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* Supporting Information
The Supporting Information is available free of charge at
Experimental procedures, spectra data for all new
C
Org. Lett. XXXX, XXX, XXX−XXX