Sulfinyl group as a novel chiral auxiliary in asymmetric heck reactions [15]

Full text of DOI:10.1021/ja980858c

J. Am. Chem. Soc. 1998, 120, 7129-7130
Table 1. Heck Reactions of 1-5 with Iodoarenesa
7129
Sulfinyl Group as a Novel Chiral Auxiliary in
Asymmetric Heck Reactions
Nuria D´ıaz Buezo, Ine´s Alonso, and Juan C. Carretero*
Departamento de Qu´ımica Orga´nica
Facultad de Ciencias, UniVersidad Auto´noma de Madrid
28049, Madrid, Spain
ReceiVed March 16, 1998
Despite the usefulness and widespread use of palladium-
catalyzed arylation and alkenylation of olefins (Heck reaction),1
successful examples of asymmetric Heck reactions are scarce and
have been reported only in the past few years, mainly using enan-
tiopure chelating diphosphines such as BINAP or (phosphinoaryl)-
oxazolines as chiral ligands.2 On the other hand, although
sulfoxides have proved to be efficient chiral auxiliaries in
asymmetric synthesis,3 especially in other crucial C-C bond
forming reactions such as Diels-Alder cycloadditions or nucleo-
phile additions, very little is known about their use in asymmetric
transition-metal-catalyzed reactions.4 To the best of our knowl-
edge we report here the first examples of asymmetric Heck
reactions using sulfoxides as chiral auxiliaries and how the sense
of the stereoselection can be controlled by appropriate choice of
the substitution at the sulfinyl moiety.5
2,3-Dihydrofuran has been the most frequently used substrate
in intermolecular asymmetric Heck reactions due to its cyclic
structure and good reactivity.6 In Table 1 are summarized the
results obtained in the palladium-catalyzed arylations of the readily
available (()-4-arylsulfinyl-2,3-dihydrofurans 1-5.7
After some experimentation, we found that the reactions
proceeded cleanly in the presence of Ag2CO3 as base. Typical
experimental conditions are as follows: ArI (3 equiv), Pd(OAc)2
(10 mol %), and Ag2CO3 (2 equiv) in DMF at 100 °C for a few
hours. These reactions took place similarly both in the absence
and in the presence of phosphine ligands (PPh3, dppp,8 or dppf8),
although in the latter case the processes were faster, giving in
satisfactory yields a mixture of 2-aryl-3-sulfinyl-2,5-dihydrofurans
A and B,9 which in many cases could be separated by flash
chromatography. However, the most interesting result concerns
the dependence of the stereoselectivity with the substitution at
the sulfoxide. Thus, regardless the electronic character of the
substitution at the aryl iodide, sulfoxides 1-4 lead predominantly
to the isomers A with moderate stereoselectivity (diastereomeric
excess (de) ) 34-56%), while the o-dimethylamino sulfoxide 5
affords the isomers B with a remarkable stereocontrol (de ) 70-
88%).10
Although from these preliminary results it is not possible to
establish a precise mechanistic explanation about the opposite
stereochemical outcome obtained from substrates 1-4 and 5, we
speculate that this different behavior could be attributed to either
a steric or a chelation control in the insertion step, respectively.
After oxidative addition, the coordination of the cationic arylpal-
ladium species1 [ArPdL2]+ with the double bond of vinyl
sulfoxides 1-4 in their s-trans conformations11 would occur
preferably from the least hindered face, that opposite to the Ar1
group, to give the complex C12 (Figure 1). Further insertion on
the double bond and â-hydrogen elimination steps would lead to
the isomer A. In contrast, due to the excellent ability of the
palladium atom to coordinate amino groups, it can be assumed
that the initial coordination of [PhPdL2]+ to the NMe2 unit of 5
(1) Recent reviews: (a) Gibson, S. E.; Middleton, R. J. Contemp. Org.
Synth. 1996, 3, 447. (b) de Meijere, A.; Meyer, F. E. Angew. Chem., Int. Ed.
Engl. 1994, 36, 2379. (c) Cabri, W.; Candiani, I. Acc. Chem. Res. 1995, 28,
2.
(2) For a review on the asymmetric Heck reaction, see: (a) Shibasaki, M.;
Boden, C. D. J.; Kojima, A. Tetrahedron 1997, 53, 7371. See also: (b)
Loiseleur, O.; Hayashi, M.; Schmees, N.; Pfaltz, A. Synthesis 1997, 1338.
(3) Recent reviews: (a) Aversa, M. C.; Barattucci, A.; Bonaccorsi, P.;
Gianneto, P. Tetrahedron: Asymmetry 1997, 8, 1339. (b) Carren˜o, C. Chem.
ReV. 1995, 95, 1717. (c) Walker, A. J. Tetrahedron: Asymmetry 1992, 3,
961.
(4) (a) Paley, R. S.; Rubio, M. B.; Ferna´ndez de la Pradilla, R.; Dorado,
R.; Hundal, G.; Mart´ınez-Ripoll, M. Organometallics 1996, 15, 4672. (b)
Tokunoh, R.; Sodeoka, M.; Aoe, K.-I.; Shibasaki, M. Tetrahedron Lett. 1995,
36, 8035. (c) Villar, J. M.; Delgado, A.; Llebaria, A.; Moreto´, J. M.
Tetrahedron: Asymmetry 1995, 6, 665. (d) Allen, J. V.; Bower, J. F.; Williams,
J. M. J. Tetrahedron: Asymmetry 1994, 5, 1895. (e) Khiar, N.; Ferna´ndez I.;
Alcudia, F. Tetrahedron Lett. 1993, 34, 123. (f) Carren˜o, C.; Garc´ıa Ruano,
J. L.; Maestro, M. C.; Mart´ın Cabrejas, L. M. Tetrahedron: Asymmetry 1993,
4, 727.
(9) The configurational assignment of stereoisomers A and B was first
established by NMR studies. Particularly, the chemical shifts of H2 and H4
were found to be excellent diagnostic criteria. H4 appears significantly more
deshielded in isomers A than in isomers B (δ4A-δ4B ) 0.1-0.5 ppm, CDCl3)
whereas the opposite behavior is observed for δH2 (δ2B-δ2A ) 0.1-0.5 ppm,
CDCl3). These remarkable spectroscopic effects might be explained on the
basis of the highly deshielding effect induced by the sulfinylic oxygen on its
hydrogen in 1,3-parallel relationship: H4 in isomers A and H2 in isomers B
in their presumed most stable conformations around the C-S bond, those
avoiding important 1,3-parallel interactions between substituents at sulfur and
at C-2 (see figures below). For NMR effects of the sulfinyl group, see: Lett,
R.; Marquet, A. Tetrahedron 1974, 30, 3379.
(5) For the use of p-tolyl vinyl sulfoxide in a palladium-catalyzed arylation,
see: Somei, M.; Yamada, F.; Ohnishi, H.; Makita, Y.; Kuriki, M. Heterocycles
1987, 26, 2823.
(6) Very recent references: (a) Hii, K. K.; Claridge, T. D. W.; Brown, J.
M. Angew. Chem., Int. Ed. Engl. 1997, 36, 984. (b) Hillers, S.; Sartori, S.;
Reiser, O. J. Am. Chem. Soc. 1996, 118, 2087. (c) Loiseleur, O.; Meier, P.;
Pfaltz, A. Angew. Chem., Int. Ed. Engl. 1996, 35, 200.
(7) Compounds (()-1-5 were prepared by oxidation of the corresponding
thioethers (MCPBA), which were readily prepared by sulfenylation of 2,3-
dihydrofuran with methyl aryl sulfoxides: Jain, S.; Shukla, K.; Mukhopadhyay,
A.; Suryawanshi, S. N.; Bhakuni, D. S. Synth. Commun. 1990, 20, 1315.
(8) dppp ) 1,3-bis(diphenylphosphino)propane. dppf ) 1,1′-bis(diphen-
ylphosphino)ferrocene.
(10) In the absence of phosphines the stereoselectivity of the Heck reactions
of 5 was somewhat lower. For instance in the reaction with iodobenzene the
A:B ratio was 12:88 in the absence of phosphines, 8:92 in the presence of
PPh3 (20 mol %), and 6:94 in the presence of dppp or dppf (10 mol %).
(11) For conformational aspects in vinyl sulfoxides, see: Arai, I.; Takayama,
H.; Koizumi, T. Tetrahedron Lett. 1987, 28, 3689.
S0002-7863(98)00858-0 CCC: $15.00 © 1998 American Chemical Society
Published on Web 07/03/1998

7130 J. Am. Chem. Soc., Vol. 120, No. 28, 1998
Communications to the Editor
Scheme 1a
Figure 1. Proposed models for the insertion step in the Heck reaction
of 1-4 and 5.
Table 2. Heck Reaction of 10B and 12B with Iodoarenesa
a Key: (a) (i) LDA, Et2O, -78 °C; (ii) ethylene oxide; (b) (i) LDA,
-78 °C, THF; (ii) ethyl formate, -78 °C; (c) MsCl, Et3N, CH2Cl2, 0 °C;
(d) PhI, Pd(OAc)2, Ag2CO3, dppp, DMF, 100 °C, 4 h; (e) PhI, Pd(OAc)2,
Ag2CO3, dppf, DMF, 100 °C, 20 h; (f) Zn, sat. NH4Cl, THF, rt; (g) Raney
Ni, H2, EtOH, 0 °C.
prepared in 44% overall yield from (S)-o-(N,N-dimethylamino)-
phenyl methyl sulfoxide15 [(S)-24] as follows: reaction of the
R-sulfinyl anion of (S)-24 with ethylene oxide, formylation at
R-position with ethyl formate to give a mixture of hemiacetals
stereoisomers, and dehydratation with MsCl/Et3N (Scheme 1).
The Heck reaction of (R)-5 with iodobenzene under the usual
conditions afforded a 6:94 mixture of (2R,SR)-10A and (2S,SR)-
10B. After flash chromatography (2S,SR)-10B was obtained in
77% yield and its further desulfinylation by treatment with
activated powdered zinc16 led to the known (R)-2-phenyl-2,5-
dihydrofuran [(R)-25, 51% yield, ee > 96%17] whose optical
rotation was identical to the previously reported,18 proving
otherwise the stereochemical assignments previously established
by NMR for compounds A and B.9 In a similar manner, the
treatment of (2S,SR)-10B with iodobenzene yielded (3R,SR)-19
(83%), which was cleanly transformed in one-step (90%) into
enantiopure (2S,4R)-2,4-diphenyltetrahydrofuran [(2S,4R)-26, [R]
) -52.5 (c ) 1.40, CHCl3), ee > 96%17] by reaction with Raney
nickel. (2S*,4R*)-26, called Calyxolane B, has been recently
isolated from a marine sponge.19
would lead to the amino complex D,13 which would direct
intramolecularly the insertion of the aryl group (Ar2) from the
same side of the (N,N-dimethylamino)phenyl moiety to afford
finally the isomer B.
Having developed a stereoselective approach to the preparation
of 2-aryl-3-(arylsulfinyl)-2,5-dihydrofurans (A and B), it was
interesting to know if these new vinyl sulfoxides could undergo
a second Heck reaction to afford diaryl substituted dihydrofurans.
We were pleased to find that the major isomers B obtained from
dihydrofuran 5 reacted cleanly and in a fully stereoselective
manner under similar conditions to that described for 5, but using
longer reaction times (20 h instead of 2-6 h).14 The reaction
appears to be general (Table 2), and the resulting 3,5-diaryldihy-
drofurans (19-23) were isolated as single isomers in good yields
(70-84%). This complete asymmetric induction might be
rationalized assuming a chelated model similar to that proposed
for dihydrofuran 5, in which both the steric effects associated to
the substitution at C-2 and the coordination Pd/NMe2 in the s-trans
conformation of the unsaturated sulfoxide (10B or 12B) would
favor the insertion step from the face of the double bond opposite
to the aryl substituent at C-2.
In conclusion, it has been demonstrated that the sulfinyl group
can be used as a novel and efficient chiral auxiliary in asymmetric
Heck reactions of dihydrofurans. The best results have been
obtained using o-(N,N-dimethylamino)phenyl sulfoxides, in which
the presumed coordination of the Pd atom with the nitrogen
determines a high asymmetric induction in the key insertion step.
Acknowledgment. This work was supported by the DGICYT (project
PB96-0021). N.D. acknowledges the Ministerio de Educacio´n y Cultura
for a fellowship. We also thank Prof. Antonio M. Echavarren for some
helpful comments and Miss Cristina Mastro for some previous experi-
mental work.
To apply this methodology to the preparation of optically pure
compounds, enantiopure sulfoxides 1-5 were required. Com-
pound (R)-5 (enantiomeric excess (ee) > 96%) was readily
Supporting Information Available: Experimental procedures and
spectral data of the new compounds (10 pages, print/PDF). See any
current masthead page for ordering information and Web access
instructions.
(12) Taking into account the moderate palladium-coordinating ability of
the sulfinyl group (see for instance ref 4b), a prior complexation of the aryl
palladium cation with either the sulfinylic oxygen or the sulfur lone pair of
sulfoxides 1-4, followed by π-complexation directed by the Pd atom, cannot
be ruled out as a feasible alternative mechanism.
(13) For somewhat related Pd-N coordinated complexes proposed in the
Heck reaction of acyclic nitrogen-containing vinyl ethers, see: (a) Larhed,
M.; Andersson, C.; Hallberg, A. Tetrahedron 1994, 50, 285. (b) Andersson,
C.; Larsson, J.; Hallberg, A. J. Org. Chem. 1990, 55, 5757. See also: Krafft,
M. E.; Wilson, A. M.; Fu, Z.; Procter, M. J.; Dasse, O. A. J. Org. Chem.
1998, 63, 1748.
JA980858C
(15) Compound (S)-24 was prepared using the DAG methodology: Ferna´n-
dez, I.; Khiar, N.; Llera, J. M.; Alcudia, J. J. Org. Chem. 1992, 57, 6789.
(16) Holton, R. A.; Crouse, D. J.; Williams, A. D.; Kennedy, R. M. J.
Org. Chem. 1987, 52, 2317.
1
(17) The optical purities were determined by H NMR in the presence of
Pr(hfc)3 [Praseodymium tris[3-(heptafluoropropylhydroxymethylene)-(+)-
camphorate].
(18) [R] ) +282 (c ) 0.50, CHCl3, 24 °C); [R] lit.2b ) +280 (c ) 1.06,
CHCl3, 24 °C, ee ) 97%).
(14) On the contrary, no reaction was observed after treatment of 6A and
10A with iodobenzene (3 equiv), Pd(OAc)2 (10 mol %), dppf (20 mol %),
and Ag2CO3 (2 equiv) in DMF at 100 °C for 20 h.
(19) Rodr´ıguez, A. D.; Co´bar, O. M.; Padilla, O. L. J. Nat. Prod. 1997,
60, 915.