FULL PAPER
Procedures for the Transformation of 3cnt to Dipep-
tide Derivative 6.
Procedures for the Transformation of 3cnt to Schiff-
base Ligand 10and Palladium Complex 11.
(1R,3S,5S,7S)-(À )-3-((((4’-(tert-Butyl)-6-methyl-[1,1’-biphen-
yl]-3-yl)oxy)sulfonyl)amino)-5-(4’-fluoro-[1,1’-biphenyl]-4-yl)
adamantane-1-carboxylic acid ((À )-5). (+)-3cnt (83.0 mg,
0.117 mmol) and KOH (256 mg, 4.56 mmol) were weighed into
a flask, which was then purged with nitrogen. To this was added
MeOH (0.84 mL) and H2O (0.84 mL), and it was then warmed
to refluxing temperature in an oil bath and stirred for 15 h. The
mixture was quenched with 1 N HCl aq., extracted with EtOAc
three times, dried over NaSO4, filtered and concentrated on a
rotary evaporator to give the title compound (64.6 mg,
(+)-4’-(tert-Butyl)-6-methyl-[1,1’-biphenyl]-3-yl-3-(4’-fluoro-
[1,1’-biphenyl]-4-yl)-5-(hydroxymethyl)adamantan-1-yl)sul-
famate ((+)-7). To
a suspension of LiAlH4 (140 mg,
3.69 mmol) in THF (0.61 mL) was slowly added a solution of
(+)-3cnt (871 mg, 1.23 mmol) in THF (3.2 mL) via cannula at
°
0 C. The reaction mixture was then warmed to refluxing
temperature in an oil bath and stirred for 3 h. The mixture was
°
then cooled to 0 C and carefully quenched with Na2SO4 ·10H2O
followed by addition of Na2SO4. The white slurry was filtered
through Celite pad and concentrated on a rotary evaporator to
give the title compound (674 mg, 1.03 mmol) (84% yield). The
crude mixture was used without purification for the next step.
1H NMR (500 MHz, CDCl3): δ 1.36 (s, 9H), 1.43–1.49 (m, 4H),
1.60–1.68 (m, 4H), 1.74–1.88 (m, 4H), 2.19 (s, 3H), 2.35–2.40
(m, 1H), 2.79 (brs, 3H), 3.36 (s, 2H), 6.71–6.74 (m, 2H), 7.07–
7.13 (m, 3H), 7.22–7.25 (m, 2H), 7.38–7.42 (m, 4H), 7.46–7.54
(m, 4H). 13C{1H} NMR (125 MHz, CDCl3): δ 19.6, 30.0, 31.4,
34.5, 37.1, 37.9, 38.8, 41.5, 43.7, 44.4, 46.4, 49.4, 50.9, 72.5,
114.1, 115.5 (d, J=21.6 Hz), 116.8, 124.9, 125.4, 126.8, 127.0,
128.5 (d, J=7.2 Hz), 128.7, 131.3, 136.9, 137.8, 138.7, 142.8,
148.3, 149.6, 153.9, 162.3 (d, J=245.9 Hz). HRMS (ESI) calcd
for C23H27FNO (MÀ C17H19O3SÀ +2H+) 352.2071, found
352.2068. [α]D22 +0.54 (c 1.00, CHCl3).
1
96.8 μmol) (83% yield) as a white solid. H NMR (400 MHz,
CDCl3): δ 1.33 (s, 9H), 1.83–1.95 (m, 4H), 2.02–2.11 (m, 4H),
2.14–2.20 (m, 2H), 2.21–2.25 (m, 2H), 2.25 (s, 3H), 2.44–2.52
(m, 1H), 4.86 (brs, 1H), 7.08–7.13 (m, 2H), 7.16–7.26 (m, 5H),
7.35–7.42 (m, 4H), 7.45–7.53 (m, 4H). 13C{1H} NMR
(100 MHz, CDCl3): δ 20.0, 29.5, 31.3, 34.5, 36.6, 38.5, 40.5,
40.6, 42.7, 42.8, 43.4, 46.8, 56.7, 115.6 (d, J=21.9 Hz), 120.0,
122.9, 125.1, 125.3, 127.0, 128.5 (d, J=7.6 Hz), 128.7, 131.4,
134.3, 136.8, 137.6, 138.3, 143.2, 146.7, 148.1, 150.1, 162.4 (d,
J=246.1 Hz), 181.5. HRMS (ESI) calcd for C40H42FNNaO5S
25
(M+Na+) 690.2660, found 690.2658. [α]D À 22.06 (c 0.14,
°
CHCl3). mp: 94–96 C.
(1R,3S,5S,7S)-(+)-Methyl 3-((((4’-(tert-butyl)-6-methyl-[1,1’-
biphenyl]-3-yl)oxy)sulfonyl)amino)-5-(4’-fluoro-[1,1’-biphen-
yl]-4-yl)adamantane-1-carboxamido)adamantane-1-carbox-
ylate ((+)-6). (À )-5 (45.0 mg, 67.4 μmol), methyl 3-amino-
adamantane-1-carboxylate (15.5 mg, 74.1 μmol), and HBTU
(28.1 mg, 74.1 μmol) were weighed into a flask, which was
then purged with nitrogen. To this was added MeCN (5.4 mL)
and DIPEA (9.6 mg, 74.1 μmol). The mixture was stirred at
(+)-(3-Amino-5-(4’-fluoro-[1,1’-biphenyl]-4-yl)-adaman-
tane-1-yl) methanol ((+)-8). Alcohol 7 (76.7 mg, 0.117 mmol)
and NaOH (188 mg, 4.69 mmol) were dissolved in MeOH
°
(4.7 mL). The mixture was sealed and stirred at 150 C in an oil
bath for 24 h. The resulting mixture was cooled to room
temperature and acidified with 1 N HCl aq. The water layer was
washed with Et2O, followed by addition of NaOH until pH 12.
The mixture was extracted with EtOAc three times, dried over
Na2SO4, filtered, and concentrated on a rotary evaporator to
give the title compound (37.6 mg, 0.107 mmol) (92% yield) as
°
60 C in an oil bath for 19 h. The resulting mixture was
quenched with brine, extracted with CHCl3 three times, and
washed with 1 N HCl aq., sat. NaHCO3 aq., and brine. The
organic layer was dried over Na2SO4, filtered, and concentrated
on a rotary evaporator. The crude mixture was purified by
PTLC on silica gel (hexane/EtOAc=4/1) to give the title
compound (32.9 mg, 38.3 μmol) (57% yield, 90% ee) as a white
1
a white solid. H NMR (400 MHz, CD3OD): δ 1.38–1.45 (m,
2H), 1.45–1.55 (m, 2H), 1.56–1.70 (m, 4H), 1.70–1.86 (m, 4H),
2.28–2.48 (m, 1H), 3.27 (s, 2H), 7.10–7.18 (m, 2H), 7.40–7.47
(m, 2H), 7.48–7.56 (m, 2H), 7.56–7.64 (m, 2H). 13C{1H} NMR
(125 MHz, CD3OD): δ 31.5, 38.3, 39.0, 39.8, 42.8, 44.7, 44.9,
46.7, 50.1, 51.2, 72.9, 116.4 (d, J=21.6 Hz), 126.5, 127.7,
129.6 (d, J=8.4 Hz), 138.5, 138.8, 150.1, 163.7 (d, J=
244.7 Hz). HRMS (ESI) calcd for C23H27FNO (M+H+)
352.2071, found 352.2066. [α]D25 +0.44 (c 1.00, MeOH). mp:
1
solid. H NMR (400 MHz, CDCl3): δ 1.35 (s, 9H), 1.62–1.66
(m, 2H), 1.80–1.85 (m, 6H), 1.87–1.91 (m, 2H), 1.92–2.00 (m,
6H), 2.04–2.14 (m, 6H), 2.15–2.22 (m, 4H), 2.27 (s, 3H), 2.47–
2.53 (m, 1H), 3.65 (s, 3H), 4.63 (brs, 1H), 5.28 (brs, 1H), 7.09–
7.15 (m, 2H), 7.17–7.20 (m, 2H), 7.21–7.24 (m, 2H), 7.25–7.28
(m, 1H), 7.37–7.43 (m, 4H), 7.48–7.55 (m, 4H). 13C{1H} NMR
(125 MHz, CDCl3): δ 20.0, 29.0, 29.8, 31.3, 34.5, 35.1, 37.3,
37.8, 38.8, 40.5, 40.6, 42.3, 42.5, 43.5, 43.9, 44.0, 46.7, 51.7,
51.8, 57.0, 115.6 (d, J=21.6 Hz), 119.9, 122.8, 125.1, 125.3,
126.9, 128.5 (d, J=8.4 Hz), 128.7, 131.4, 134.2, 136.8, 137.6,
138.3, 143.2, 146.8, 148.1, 150.1, 162.4 (d, J=245.9 Hz),
174.8, 176.9. HRMS (ESI) calcd for C52H59FN2NaO6S (M+
Na+) 881.3970, found 881.3979. [α]D25 +3.98 (c 1.00, CHCl3).
°
128–131 C.
(+)-3-(((tert-Butyldimethylsilyl)oxy)methyl)-5-(4’-fluoro-
[1,1’-biphenyl]-4-yl)adamantan-1-amine ((+)-9). Amino alco-
hol 8 (52.2 mg, 0.149 mmol) was weighed into a flask, which
was then purged with nitrogen. To this was added DMF
(1.5 mL), imidazole (40.5 mg, 0.596 mmol), and TBSCl
(33.7 mg, 0.224 mmol). The resulting mixture was then stirred
at room temperature for 18 h. After adding 1 N NaOH aq., the
mixture was extracted with EtOAc three times, dried over
Na2SO4, filtered, and concentrated on a rotary evaporator. The
crude mixture was purified by PTLC on silica gel (CH2Cl2/
MeOH=20/1) to give the title compound (42.9 mg, 92.1 μmol)
°
mp: 102–105 C. The enantiomeric excess of the product was
determined by HPLC analysis with chiral stationary phase
column. Chiralpack IB, hexane/EtOH=4/1, flow rate 0.3 mL/
min, t1S,3R,5R,7R =29.9 min (minor), t1R,3S,5S,7S =32.0 min (major).
1
(62% yield) as a colorless oil. H NMR (400 MHz, CDCl3): δ
0.03 (s, 6H), 0.90 (s, 9H), 1.38–1.48 (m, 2H), 1.50–1.83 (m,
12H), 2.32–2.36 (m, 1H), 3.29 (s, 2H), 7.08–7.13 (m, 2H),
Adv. Synth. Catal. 2021, 363, 1662–1671
1669
© 2021 Wiley-VCH GmbH