Pd-Catalyzed Tin Hydride Addition to Z-Enynols
SCHEME 4. R Substituent-Directed Tin Hydride Addition
(alkyl groups induce high selectivity) or by steric effects
(hindered alkyl groups are rather in favor of R-isomer).
The factors governing this remarkable regioselectivity would
be close to those observed in the hydrostannation of ortho-
substituted arylalkynes (ODE).12a,b We have observed in these
later derivatives that ortho-substituents induced dramatic varia-
tions in 13C NMR data of the triple bond. On the basis of this
observation, we decided to carefully examine the CR and Câ
chemical shifts of E- and Z-enynol derivatives (Table 4).
13C NMR data depicted in Scheme 3 showed a 5.6 ppm
downfield shift in the Câ and a 2.0 ppm upfield shift in the CR
of the triple bond for Z-alkylenynol 7b compared to the
corresponding E-isomer 4b. Similarly, the signal arising from
the Câ atom is 5.8 ppm downfield and the signal from the CR
atom is 1.2 ppm upfield when E- and Z-chloroenynol 4a and
7a were compared, respectively (Scheme 3). As shown in
Table 4, a similar situation was also noted when comparing
various E- and Z-enynols having an alkyl or an aryl substituent
on the double bond. In all cases studied, we noticed that
switching from E- to Z-enynols isomers increases the difference
in the 13C NMR chemical shift of the signals arising from the
∆δCâ-CR atom from 5.0 to 7.9 ppm (entries 11, 12 and 7, 8).
To our knowledge, such observation is unprecedented.
exact origin of this syn- or Z-induced high regioselectivity
remains unclear but would be similar to those observed in the
ortho-substituent regiocontrol concept.12,18
This study shows that it is possible to predict the major or
exclusive R-isomer formation when a R substituent (regardless
of its nature) and the alkyne are on the same side of the double
bond. This “ZDE/SDE” demonstrated herein should find many
applications for the synthesis of more elaborated unsaturated
molecules.
Experimental Section
General Procedure for the Hydrostannation of Enynes.12b
Tributyltin hydride or triphenyltin hydride (13 mmol) was added
dropwise at room temperature to a solution of PdCl2(PPh3)2
(0.1 mmol) and enyne (10 mmol) in THF (15 mL). The dark brown
reaction mixture was stirred for 30 min, and more tributyltin hydride
(2 mmol) was added to the crude mixture to complete the
hydrostannation reaction. After stirring for an additional 30 min,
the solution was concentrated in vacuo. Purification by flash
chromatography on silica gel gave the desirated products.
Hydrostannation of 5b with tributyltin hydride:
(3E,5E)-4-Tributylstannanyl-deca-3,5-dien-2-ol 12b (33%); Rf
0.17 (Et2O/cyclohexane, 10/90, SiO2); IR (neat): 3330, 2956, 2924,
2871, 2854, 1633, 1463, 1418, 1376, 1340, 1291, 1101, 1069, 955,
862, 768, 742, 688 cm-1;1H NMR (300 MHz, CDCl3): δ 0.75-
0.95 (m, 18H), 1.05 (d, 3H, J ) 7.0 Hz), 1.20-1.50 (m, 17H),
1.70-1.90 (m, 2H), 4.65 (m, 1H), 5.30 (m, 2H), 6.40 (d, 1H, J )
6.4 Hz, JH-Sn ) 64.0 Hz); 13C NMR (75 MHz, CDCl3): δ 144.0
(CH), 142.7 (C), 136.1 (CH), 130.1 (CH), 64.4 (CH), 32.8 (CH2),
31.7 (CH2), 29.1 (3CH2), 27.3 (3CH2), 23.4 (CH3), 22.2 (CH2),
13.9 (CH3), 13.7 (3CH3), 10.1 (3CH2); Anal. Calcd for C22H44OSn
(443.29): C 59.61, H 10.00, found C 59.61, H 10.11.
According to these 13C NMR data, it seems that the
Z-substituent which induced electronic polarization of the triple
bond may be one of the factors17 at the origin of the observed
regioselectivity. Although at the moment, we did not succeed
in correlating the R/â ratio observed with the triple bond
polarization, these results unambiguously support that the
presence of a substituent on the Z-double bond, whatever its
nature, dictates the sense of the regioselectivity (Z-directing
effect (ZDE)). As depicted in Scheme 4, this trend in R-regi-
oselectivity was also observed with substrates having R groups
and alkyne substituents on the same side of the double bond
whatever its substitution degrees (syn-directing effect (SDE)).
(3E,5Z)-3-Tributylstannanyl-deca-3,5-dien-2-ol 13b (16%); Rf
0.49 (Et2O/cyclohexane, 10/90, SiO2); IR (neat): 3420, 2956, 2923,
2871, 2854, 1637, 1576, 1463, 1419, 1340, 1291, 1247, 1181, 1149,
1070, 1049, 964, 940, 865, 768, 742, 665 cm-1 1H NMR
;
(300 MHz, CDCl3): δ 0.70-0.95 (m, 18H), 1.15 (d, 3H, J ) 6.4
Hz), 1.20-1.50 (m, 17H), 2.05 (m, 2H), 4.95 (m, 1H), 5.60 (m,
1H), 5.95 (dd, 1H, J ) 10.7 Hz, J ) 1.5 Hz, JH-Sn ) 64.0 Hz),
6.70 (m, 1H); 13C NMR (75 MHz, CDCl3): δ 152.1 (C), 136.7
(CH), 136.1 (CH), 125.6 (CH), 69.0 (CH), 32.5 (CH2), 31.5 (CH2),
29.2 (3CH2), 27.5 (3CH2), 24.2 (CH3), 22.3 (CH2), 14.0 (CH3),
13.7 (3CH3), 10.5 (3CH2);. Anal. Calcd for C22H44OSn (443.29):
C 59.61, H 10.00, found C 59.73, H 10.25.
Conclusion
In conclusion, we have succeeded in providing some evidence
for the Z- or syn-directing effect (ZDE or SDE) of the double
bond in the palladium-catalyzed tributyltin hydride addition on
various substituted enynols. High to excellent R-regioselectivity
is observed for Z-enynols bearing nonchelating alkyl substitu-
ents. Combining either steric effects (secondary and tertiary
enynols) with ZDE or SDE leads to exclusive R-isomer as
observed with Z-arylenynol or Z-chloroenynol substrates. Al-
though, 13C NMR data showed a marked electronic polarization
of the alkyne bond when Z- and E-enynols were compared, the
Hydrostannation of 8b with tributyltin hydride:
(3E,5Z)-4-Tributylstannanyl-deca-3,5-dien-2-ol 18b (75%); Rf
0.37 (Et2O/cyclohexane, 10/90, SiO2); IR (neat): 3315, 2956, 2924,
2872, 2854, 1463, 1417, 1377, 1339, 1291, 1142, 1054, 960, 927,
864, 782, 688, 662 cm-1;1H NMR (300 MHz, CDCl3): δ 0.80-
1.00 (m, 18H), 1.15 (d, 3H, J ) 6.3 Hz), 1.20-1.65 (m, 15H),
1.95 (m, 2H), 4.50 (quint, 1H, J ) 6.4 Hz), 5.25 (m, 1H), 5.60 (m,
1H, JH-Sn ) 65.6 Hz), 6.00 (dq, 1H, J ) 11.4 Hz, J ) 1.8 Hz); 13
C
(16) (a) Pottier, L. R.; Peyrat, J.-F.; Alami, M.; Brion, J.-D. Tetrahedron
Lett. 2004, 45, 4035-4038. (b) Pottier, L. R.; Peyrat, J.-F.; Alami, M.;
Brion, J.-D. Synlett. 2004, 1503.
NMR (75 MHz, CDCl3): δ 143.9 (CH), 142.8 (C), 130.1 (CH),
127.7 (CH), 65.9 (CH), 31.8 (CH2), 29.0 (3CH2), 28.5 (CH2), 27.4
(17) (a) Rubin, M.; Trofimov, A.; Gevorgyan, V. J. Am. Chem. Soc.
2005, 127, 10243. (b) Kleinpeter, E.; Schulenburg, A. J. Org. Chem. 2006,
71, 3869.
(18) Hamze, A.; Provot, O.; Alami, M.; Brion, J.-D. Org. Lett. 2005, 7,
5625.
J. Org. Chem, Vol. 72, No. 10, 2007 3873