B. Breit and Y. Schmidt
stirred until complete conversion of the allylic alcohol was observed
(TLC). The mixture was filtered through Celite, rinsed with CH2Cl2 and
the filtrate was evaporated under reduced pressure. Purification by flash
chromatography (silica, petroleum ether/tert-butyl methyl ether (TBME)
10:1) furnished 24 (2.15 g, 65%) as a yellow oil. Rf =0.80 (petroleum
ether/TBME 10:1); 1H NMR (400.130 MHz, CDCl3): d=0.85 (t, 3J=
7.0 Hz, 3H; 8-H), 1.00 (d, 3J=6.6 Hz, 3H; 2-CH3), 1.11–1.30 (m, 4H; 6-
H, 7-H), 1.60 (mc, 2H; 5-H), 2.21 (qq, 3J=6.9, 6.6 Hz, 1H; 2-H), 4.88 (d,
4J=0.8 Hz, 1H; 9-H), 5.01 (d, 4J=0.8 Hz, 1H; 9-H), 5.35 (appt, J=
6.4 Hz, 1H; 4-H), 6.89–6.93 (m, 1H; Ar-H), 7.23–7.33 (m, 10H; Ar-H),
7.38 (mc, 2H; Ar-H), 8.06–8.10 ppm (m, 1H; Ar-H); 13C NMR
(100.613 MHz, CDCl3): d=14.0, 22.6, 22.7, 22.9, 27.8, 30.5, 33.5, 77.8,
Conclusion
Synthesizing trisubstituted olefins in a stereodefined manner
is still an unsolved problem for a wide range of substrates.
Many existing methods for the synthesis of trisubstituted
olefins are restricted to the necessary presence of adjacent
EWGs for control of the geometry of the newly formed
double bond or suffer from poor regioselectivity. We have
presented a new method for the diversity-oriented, stereose-
lective synthesis of trisubstituted olefins by application of a
copper-mediated directed allylic substitution reaction of 2-
substituted allylic o-DPPB esters with Grignard reagents.
More than thirty differently trisubstituted olefins without
adjacent electron withdrawing groups were synthesized by
this method. For branched R1 substituents at the alkenic 2-
position, in all cases, high stereoselectivity in favor of the E
alkene was observed, independent of the nature of the R2
substituent or Grignard reagent. Notably, on application of
sp2 Grignard reagents as nucleophiles, the corresponding Z
alkenes were formed stereoselectively. Additional features
of the reaction sequence are the use of inexpensive copper
salts as the source of the transition-metal reagent and the
very good yields achieved in the allylic substitution step. Be-
cause our method uses simple starting materials, an a-meth-
ylene aldehyde and two organometallic compounds, we en-
vision its use as a diversity-oriented approach towards tri-
substituted olefins.[22]
109.2, 128.2, 128.4 (d, J
128.6 (d, J(C,P)=3.8 Hz, 2C), 130.6 (d, J
(d, J(C,P)=6.1 Hz, 2C), 134.2 (d, J(C,P)=6.1 Hz), 134.4, 134.9 (d, J-
(C,P)=18.7 Hz), 138.2 (d, J(C,P)=9.7 Hz), 138.4 (d, J(C,P)=9.8 Hz),
140.6 (d, (C,P)=27.4 Hz), 154.4, 166.1 ppm (d, (C,P)=2.4 Hz);
A
ACHTUNGTREN(NUGN C,P)=1.9 Hz, 2C),
A
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
A
R
ACHTUNGTRENNUNG
J
N
JACHTUNGTRENNUNG
31P NMR (161.976 MHz, CDCl3): d=À4.76 ppm; MS (CI, NH3, 130 eV):
m/z (%): 445 [M+H]+ (100), 305 (33), 139 (21); elemental analysis calcd
(%) for C29H33O2P (444.54): C 78.35, H 7.48; found: C 78.20, H 7.59.
AHCTUNGTERG(NNUN 7R)-7,11-Dimethyl-6-methylenedodec-10-en-5-yl 2-(diphenylphosphino)-
benzoate (39): A solution of (7R)-7,11-dimethyl-6-methylenedodec-10-
en-5-ol (245 mg, 1.09 mmol) in CH2Cl2 was added to a suspension of o-
DPPBA (404 mg, 1.32 mmol, 1.2 equiv), DCC (272 mg, 1.32 mmol,
1.2 equiv), and DMAP (161 mg, 1.32 mmol, 1.2 equiv) in CH2Cl2
(5.0 mL) at RT. The reaction mixture was stirred until complete conver-
sion of the allylic alcohol was observed (TLC). The mixture was filtered
over Celite, rinsed with CH2Cl2, and the filtrate was evaporated under re-
duced pressure. Purification by flash chromatography (silica, petroleum
ether/MTBE 20:1) furnished 39 (550 mg, 98%, d.r.=1:1) as a yellow oil.
Rf =0.70 (petroleum ether/TBME 15:1); 1H NMR (400.130 MHz,
CDCl3): d=0.84 (t, 3J=7.0 Hz, 3H; 1-H), 0.99
[0.97] (d, 3J=6.8 Hz, 3H;
ACHTUNGTRENNUNG
7-CH3), 1.13–1.34 (m, 5H; 2-H, 3-HA, 8-H), 1.40–1.49 (m, 1H; 3-HB);
4
1.51ACHTUNGTREN[UNGN 1.56] (d, J=0.8 Hz, 3H; 11-CH3), 1.53–1.62 (m, 2H; 4-H), 1.64ACHTUNGTRENNUNG
4
AHCTUNGTRENNUNG
Experimental Section
CHAHB), 5.31 (mc, 1H; 5-H), 6.95–7.03 (m, 1H; Ar-H), 7.24–7.35 (m,
10H; Ar-H), 7.36–7.55 (m, 2H; Ar-H), [7.70 (mc, 1H; Ar-H)], 8.07–
8.11 ppm (m, 1H; Ar-H); 13C NMR (100.613 MHz, CDCl3): d=14.0 (C-
General remarks: All reactions were carried out under an atmosphere of
argon 5.0 (Sꢀdwest-Gas) in dried glassware. Air- and moisture-sensitive
liquids and solutions were transferred by syringe. All solvents were dried
and distilled by standard procedures. Solutions were concentrated under
reduced pressure by rotary evaporation. Chromatographic purification of
products was accomplished on Merck silica gel 60 ꢃ (200–400 mesh). 1H
and 13C NMR spectra were acquired on a Varian Mercury spectrometer
(300 MHz and 75 MHz, respectively) or a Bruker AMX 400 spectrometer
(400 MHz and 101 MHz, respectively) and are referenced to an internal
TMS standard or solvent signals (CDCl3: d=7.26 ppm; C6D6: d=
7.16 ppm). Data for 1H NMR spectra are reported as follows: chemical
shift (d, in ppm), multiplicity (s, singlet; brs, broad singlet; d, doublet; t,
triplet; q, quartet; sept, septet; mc, centered multiplet; m, multiplet; app,
apparent signal), coupling constant (Hz), integration. Data for 13C NMR
spectra are reported in terms of chemical shift (d, in ppm). E/Z ratios
1), 17.7
(C-9), 27.8
77.7[77.6] (C-5), 110.2
(C,P)=7.4 Hz, 4C), 128.52 (d, J
130.68[130.72] (2C), 131.3 [131.4] ,131.9 (2C), 134.00
20.4 Hz, 2C), 134.12[134.10] (d, J(C,P)=20.5 Hz, 2C), 134.6, 153.3 ppm
N
ACHTUNGTRENNUNG
E
R
ACHTUNGTRENNUNG
N
G
ACHTUNGTRENNUNG
E
U
ACHTUNGTRENNUNG
A
E
ACHTUNGTRENNUNG
G
ACHTUNGTRENNUNG
Typical procedure for the allylic substitution with o-DPPB esters,
normal-addition method, in particular for (E)-6-isopropylundec-5-ene
(16a): CuBr·SMe2 (25.5 mg, 0.124 mmol, 0.46 equiv) was added to a solu-
tion of o-DPPB ester 24 (125 mg, 0.271 mmol) in diethyl ether (2.5 mL)
at RT. The Grignard reagent (0.6 m in diethyl ether, 0.32 mmol,
1.2 equiv) was added by syringe pump to the intensely yellow solution
over 30 min. After stirring overnight, the conversion was determined by
TLC and the reaction mixture was directly applied onto a silica gel
column. Purification by flash chromatography (n-pentane) furnished 16a
(51 mg, contained n-pentane, 88%, E/Z 93:7) as a colorless oil. Rf =0.97
(n-pentane). 1H NMR (400.132 MHz, CDCl3): d (E[Z])=0.85–0.92 (m,
6H; 1-H, 11-H), 0.99 (d, 3J=6.8 Hz, 6H; 1’-CH3), 1.24–1.38 (m, 10H; 2-
H, 3-H, 8-H, 9-H, 10-H), 1.95–2.01 (m, 4H; 4-H, 7-H), 2.20 (septd, 3J=
8.0 Hz, 4J=0.4 Hz, 1H; 12-H), 5.09 ppm (t, 3J=7.1 Hz, 1H; 5-H) [5.02
1
were determined from the H NMR spectra. Assignment of the 1H NMR
spectra were accomplished by H,H-COSY experiments and the 13C NMR
spectra by C,H-COSY experiments. The shift values, given in square
brackets, refer to the differing values for the second isomer. The stereo-
genic centers are indicated by an asterisk (*). 2D-NOESY or 2D-
ROESY experiments confirmed the assignment of E and Z configura-
tions, respectively. HRMS were obtained on a Finnigan MAT 8200 instru-
ment. Elemental analysis was performed on an Elementar vario instru-
ment (Fa. Elementar Analysensysteme GmbH).
Typical procedure for the preparation of o-DPPB esters from allylic alco-
hols, in particular for 2-methyl-3-methyleneoctan-4-yl-2-(diphenylphos-
(appt, 3J=7.0 Hz, 1H; 7-H]; 13C NMR (100.613 MHz, CDCl3):
d
phino)benzoate (24):
A
solution of 2-methyl-3-methyleneoctan-4-ol
(E[Z])=14.2 (2C; C-1, C-11), 22.4 (2C; 1’-CH3), 22.5, 22.7, 27.5 (C-4)*,
29.3, 29.7 (C-8)*, 32.4, 32.5, 34.4 (C-12), 122.3 (C-7), [123.1 (C-7)],
145.7 ppm (C-6); MS (CI, NH3, 130 eV): m/z (%): 214 [M+NH4]+ (100),
197 [M+H]+ (25), 196 [M]+ (26), 140 (14); MS (EI, 70 eV): m/z (%): 196
(26), 111 (11), 97 (47), 84 (38), 83 (83), 81 (14), 70 (19), 69 (100), 67 (16),
(1.12 g, 7.16 mmol) in CH2Cl2 was added to a suspension of o-DPPBA
(2.19 g, 7.14 mmol, 1.0 equiv), dicyclohexylcarbodiimide (DCC; 1.47 g,
7.14 mmol, 1.0 equiv), and -dimethylaminopyridine (DMAP; 872 mg,
7.14 mmol, 1.0 equiv) in CH2Cl2 (25 mL) at RT. The reaction mixture was
11786
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 11780 – 11788