The Journal of Organic Chemistry
Note
overnight, before it was diluted with ethyl acetate and 1 M KHSO4 was
added. After extraction with ethyl acetate, the organic layers were dried
over Na2SO4 and concentrated in vacuo, and the crude product was
purified by flash chromatography (hexanes/ethyl acetate).
CDCl3): δ = 27.8, 38.4, 52.0, 54.8, 56.4, 82.9, 115.5 (q, JF = 288 Hz),
118.1, 127.4, 127.5, 128.2, 128.7, 128.8, 129.3, 135.1, 136.0, 138.6,
156.6 (d, JF = 38.0 Hz), 168.9, 169.2. Minor diastereomer (S,2S,2R)-4c
1
(9%): H NMR (400 MHz, CDCl3, selected signals): δ = 1.22 (s, 9
tert-Butyl (S)-N-Trifluoroacetyl-phenylalanyl-(2R,3S)-(1-
methylallyl)glycinate (3a). By following the general procedure for
Ru-catalyzed allylic alkylation of dipeptide ester enolates, 3a (405 mg,
0.95 mmol, 95% yield) was obtained from allyl benzoate (S)-2d (176
mg, 1.00 mmol, 97% ee) and 1a (749 mg, 2.00 mmol) as a colorless
solid consisting of a mixture of mainly branched (97% rs),
diastereomeric allylation products with a diastereomeric ratio of
H), 3.50 (dd, J = 8.7, 8.7 Hz, 1H). Minor diastereomer (S,2R,3S)-5c
(6%): H NMR (400 MHz, CDCl3, selected signals): δ = 1.22 (s, 9
1
H), 3.56 (dd, J = 8.3, 8.3 Hz, 1H). The 1H and 13C NMR spectral data
of the minor linear regioisomers 7c and 8c were in good agreement
with the literature data.13b HPLC (Reprosil, n-hexane/iPrOH = 99:1,
1.0 mL/min, 210 nm): tR [(S,2S,3R)-4c] = 8.85′ (9%), tR [(S,2S,3S)-
6c] = 10.04′ (0%), tR [(S,2R,3S)- 5c] = 13.44′ (6%), tR [(S,2R,3R)-3c]
= 15.49′ (62%), tR [(S,S)-8c] = 18.76′ (4%), tR [(S,R)-7c] = 23.68′
(19%); HRMS (CI) m/z calcd for C26H30F3N2O4 [M + H]+:
491.2152; found: 491.2148.
74:20:3:0 in favor of the (S,2R,3S)-isomer. Mp 97−98 °C; [α]20
=
D
−11.4° (c = 1.0, CHCl3). Major diastereomer (S,2R,3S)-3a (74%): 1H
NMR (400 MHz, CDCl3): δ = 0.93 (d, J = 7.0 Hz, 3 H), 1.43 (s, 9 H),
2.49 (m, 1 H), 3.10 (m, 2 H), 4.43 (dd, J = 8.3, 4.6 Hz, 1 H), 4.73 (dt,
J = 7.9, 6.0 Hz, 1 H), 4.92 (ddd, J = 17.1, 1.3, 1.3 Hz, 1 H), 5.01 (ddd,
J = 10.3, 1.3, 1.3 Hz, 1 H), 5.55 (m, 1 H), 6.17 (d, J = 8.3 Hz, 1H),
7.29 (m, 5 H), 7.48 (m, 1 H); 13C NMR (100 MHz, CDCl3): δ = 15.2,
28.0, 38.7, 40.4, 54.8, 56.6, 82.8, 115.6 (q, JF = 288 Hz), 116.2, 127.5,
128.9, 129.2, 135.5, 138.2, 156.6 (d, JF = 37 Hz), 169.0, 169.5. Minor
diastereomer (S,2S,3R)-4a (20%): 1H NMR (400 MHz, CDCl3,
selected signals): δ = 0.99 (d, J = 7.4 Hz, 1 H), 1.48 (s, 9 H), 2.69 (m,
1 H), 4.43 (dd, J = 8.3, 5.0 Hz, 1 H), 6.09 (d, J = 8.2 Hz, 1 H); 13C
NMR (100 MHz, CDCl3, selected signals): δ = 15.8, 39.1, 40.2, 54.7,
56.9, 82.6, 115.6 (q, JF = 288 Hz), 116.9, 128.8, 129.4, 135.2, 137.4,
169.0, 169.5; HPLC (Reprosil, n-hexane/iPrOH = 99:1, 1.0 mL/min,
210 nm): tR [(S,2S,3S)-4a] = 14.64′ (21%), tR [(S,2R,3S)-3a] = 21.61′
(79%); HRMS (CI) m/z calcd for C21H28F3N2O4 [M + H]+:
429.1996, found: 429.2007; Analysis calcd for C21H27F3N2O4: C,
58.87, H, 6.35, N, 6.54; found: C, 59.25, H, 6.56, N, 6.33.
tert-Butyl (S)-N-trifluoroacetyl-phenylalanyl-(2R,3S)-(1-
phenylallyl)glycinate (5c). Following the general procedure for
Ru-catalyzed allylic alkylation of dipeptide ester enolates 5c (390 mg,
0.80 mmol, 80% yield) was obtained from allyl acetate (S)-2c (176 mg,
1.00 mmol, 97% ee) and 1a (749 mg, 2.00 mmol) as a colorless solid
consisting of a mixture of mainly branched (84% rs), diastereomeric
allylation products with a diastereomeric ratio of 4:1:73:6 in favor of
the (S,2R,3S)-isomer. [α]20 = −32.3° (c = 1.0, CHCl3).
D
Major diastereomer (S,2R,3S)-5c (87%): 1H NMR (400 MHz,
CDCl3): δ = 1.22 (s, 9 H, 11-H), 3.06 (d, J = 6.9 Hz, 2 H), 3.57 (dd, J
= 8.4, 8.4 Hz, 1H), 4.73 (dt, J = 7.4, 7.4 Hz, 1 H), 4.75 (dd, J = 8.1, 8.1
Hz, 1 H), 5.11 (ddd, J = 16.8, 1.1, 1.1 Hz, 1 H), 5.12 (ddd, J = 9.5, 1.1,
1.1 Hz, 1 H), 5.84 (ddd, J = 16.8, 10.3, 8.8 Hz, 1 H), 6.25 (d, J = 7.1
Hz, 1 H), 7.06 (d, J = 7.7 Hz, 1 H), 7.28 (m, 10 H). 13C NMR (100
MHz, CDCl3): δ = 27.6, 38.4, 53.0, 54.6, 56.7, 82.5, 115.6 (q, JF = 288
Hz), 118.3, 127.4, 127.4, 128.3, 128.5, 128.8, 129.2, 135.2, 136.2,
138.7, 156.6 (d, JF = 38.2 Hz), 169.1, 169.5. Minor diastereomer
(S,2S,3S)-6c (6%): 1H NMR (400 MHz, CDCl3, selected signals): δ =
1.39 (s, 9 H), 3.69 (dd, J = 7.7, 7.7 Hz, 1H), 6.22 (d, J = 7.1 Hz, 1 H).
Minor diastereomer (S,2R,3R)-3c (4%): 1H NMR (400 MHz, CDCl3,
selected signals): δ = 1.36 (s, 9 H), 3.72 (dd, J = 7.8, 7.8 Hz, 1 H). The
1H and 13C NMR spectral data of the minor linear regioisomer 7c and
tert-Butyl (S)-N-Trifluoroacetyl-phenylalanyl-(2R,3S)-(1-
ethylallyl)glycinate (3b). By following the general procedure for
Ru-catalyzed allylic alkylation of dipeptide ester enolates, 3b (413 mg,
0.97 mmol, 97% yield) was obtained from allyl benzoate (S)-2b (190
mg, 1.00 mmol, 97% ee) and 1a (749 mg of 2.00 mmol) as a colorless
solid consisting of a mixture of mainly branched (95% rs),
diastereomeric allylation products with a diastereomeric ratio of
8c were in good agreement with the literature data.13b HPLC
(Reprosil, n-hexane/iPrOH = 99:1, 1.0 mL/min, 210 nm): tR
[(S,2S,3R)-4c] = 8.85′ (1%), tR [(S,2S,3S)-6c] = 10.04′ (6%), tR
[(S,2R,3S)-5c] = 13.44′ (73%), tR [(S,2R,3R)-3c] = 15.49′ (4%), tR
[(S,S)-8c] = 18.76′ (3%), tR [(S,R)-7c] = 23.68′ (13%); HRMS (CI)
m/z calcd for C26H30F3N2O4 [M + H]+: 491.2152; found: 491.2153;
Analysis calcd for C26H29F3N2O4): C, 63.66, H, 5.96, N, 5.71; found:
C, 63.79, H, 5.84, N, 5.76.
73:19:3:0 in favor of the (S,2R,3S)-isomer. Mp 77−81 °C; [α]20
=
D
−1.4° (c = 1.0, CHCl3). Major diastereomer (S,2R,3S)-3b) (73%): 1H
NMR (400 MHz, CDCl3): δ = 0.85 (t, J = 7.4 Hz, 3 H), 1.24 (m, 2
H), 1.44 (s, 9 H), 2.02 (tdd, J = 9.8, 5.8, 5.8, Hz, 1 H), 3.12 (m, 2 H),
4.42 (dd, J = 8.4, 5.2 Hz, 1 H), 4.74 (m, 1 H), 4.85 (ddd, J = 17.0, 1.1,
1.1 Hz, 1 H), 5.05 (ddd, J = 10.2, 1.7, 1.7 Hz, 1 H), 5.39 (m, 1 H),
6.28 (d, J = 8.7 Hz, 1 H), 7.27 (m, 5 H), 7.65 (m, 1 H); 13C NMR
(100 MHz, CDCl3): δ = 11.7, 23.6, 28.0, 38.7, 49.0, 54.9, 55.8, 82.9,
115.6 (q, JF = 288 Hz), 118.4, 127.4, 128.9, 129.3, 135.4, 136.3, 156.7
(d, JF = 38 Hz), 169.0, 169.6. Minor diastereomer (S,2S,3S)-4b (19%):
1H NMR (400 MHz, CDCl3, selected signals): δ = 0.99 (t, J = 7.4 Hz,
tert-Butyl (S)-N-trifluoroacetyl-O-(tert-butyldiphenylsilyl)-
seryl-(2R,3R)-(1-phenylallyl)-glycinate (3d). Following the general
procedure for Ru-catalyzed allylic alkylation of dipeptide ester enolates
3d (447 mg, 0.67 mmol, 67% yield) was obtained from allyl acetate
(R)-2c (176 mg, 1.00 mmol, 98% ee) and 1b (718 mg, 1.30 mmol) as
a colorless solid consisting of a mixture of mainly branched (90% rs),
diastereomeric allylation products with a diastereomeric ratio of
1 H), 1.48 (s, 9 H), 2.69 (m, 1 H), 4.43 (dd, J = 8.3, 5.0 Hz, 1 H), 6.09
(d, J = 8.2 Hz, 1 H); 13C NMR (100 MHz, CDCl3, selected signals): δ
= 11.6, 23.5, 28.0, 38.1, 49.0, 54.9, 55.8, 82.6, 118.6, 127.4, 128.7,
129.3, 135.2, 135.8, 169.4, 170.0; HPLC (Reprosil, n-hexane/iPrOH =
99:1, 1.0 mL/min, 210 nm): tR [(S,2S,3S)-4b] = 13.15′ (20%), ttR
[(S,2R,3S)-3b] = 20.48′ (74%), tR [(S,2R,3R)-5b] = 22.61′ (3%);
HRMS (CI) m/z calcd for C22H30F3N2O4 [M + H]+: 443.2152; found:
443.2150.
tert-Butyl (S)-N-Trifluoroacetyl-phenylalanyl-(2R,3R)-(1-
phenylallyl)glycinate (3c). By following the general procedure for
Ru-catalyzed allylic alkylation of dipeptide ester enolates, 3c (383 mg,
0.78 mmol, 78% yield) was obtained from allyl acetate (R)-2c (176
mg, 1.00 mmol, 99% ee) and 1a (749 mg 2.00 mmol) as a colorless
solid consisting of a mixture of mainly branched (77% rs),
diastereomeric allylation products with a diastereomeric ratio of
72:15:3:0 in favor of the (S,2R,3R)-isomer. Mp 48−50 °C; [α]20
−6.3° (c = 1.0, CHCl3).
=
D
Major diastereomer (S,2R,3R)-3d (72%): 1H NMR (400 MHz,
CDCl3): δ = 1.09 (s, 9 H), 1.39 (s, 9 H), 3.56 (dd, J = 10.4, 6.0 Hz, 1
H), 3.76 (dd, J = 8.8, 6.2 Hz, 1 H), 3.89 (dd, J = 10.4, 4.3 Hz, 1 H),
4.45 (ddd, J = 6.3, 6.3, 4.3 Hz, 1 H), 4.92 (dd, J = 8.9, 6.8 Hz, 1 H),
5.08−5.15 (m, 2 H), 6.04 (ddd, J = 16.8, 10.4, 8.5 Hz, 1 H), 6.55 (d, J
= 8.9 Hz, 1 H), 7.08−7.71 (m, 16 H); 13C NMR (100 MHz, CDCl3):
δ = 19.2, 26.8, 27.9, 52.6, 54.6, 56.4, 63.3, 82.8, 118.1, 127.3, 127.9,
128.1, 128.5, 130.2, 132.0, 132.4, 135.4, 135.5, 135.6, 136.0, 138.7,
167.5, 169.2. The signals of C-12 and C-13 were not found. LC-MS
(Luna C18(2) 5 cm, 3 μm, H2O/ACN = 40:60 to 20:80, 1.0 mL/min,
254 nm, ESI−): tR = 9.00′ (19%, m/z 667); tR = 9.97′ (81%, m/z 667);
HRMS (CI) m/z calcd for C36H44F3N2O5Si [M + H]+: 669.2966;
found: 669.2967; Analysis calcd for C36H43F3N2O5Si: C, 64.65, H,
6.48, N, 4.19; found C, 64.31, H, 6.23, N, 4.37.
62:9:6:0 in favor of the (S,2R,3R)-isomer. Mp 122−130 °C; [α]20
=
D
+10.1° (c = 1.0, CHCl3). Major diastereomer (S,2R,3R)-3c (62%): 1H
NMR (400 MHz, CDCl3): δ = 1.36 (s, 9 H), 2.93 (d, J = 6.8 Hz, 2 H),
3.71 (dd, J = 7.5, 7.5 Hz, 1H), 4.63 (dt, J = 7.4, 7.1 Hz, 1 H), 4.84 (dd,
J = 8.7, 6.5 Hz, 1 H), 5.07 (ddd, J = 17.0, 1.1, 1.1 Hz, 1 H), 5.17 (ddd,
J = 10.3, 1.1, 1.1 Hz, 1 H), 5.93 (ddd, J = 17.0, 10.3, 8.3 Hz, 1 H), 6.06
(d, J = 8.6 Hz, 1 H), 7.05−7.33 (m, 11 H). 13C NMR (100 MHz,
(S)-N-Trifluoroacetyl-phenylalanyl-(2R,3S)-(1-ethylallyl)-
glycyl-(S)-N-methyl-leucine Anilide (10). Following the general
procedure for Ru-catalyzed allylic alkylation of tripeptide ester enolates
8495
dx.doi.org/10.1021/jo501731y | J. Org. Chem. 2014, 79, 8491−8497