Pd-catalyzed coupling of β-hydroxy α-diazocarbonyl compounds with aryl iodides: A migratory insertion/β-hydroxy elimination sequence

Article abstract of DOI:10.1039/c0cc05523a

The coupling of β-hydroxy α-diazocarbonyl compounds with aryl halides is described, which proceeds through a Pd-catalyzed migratory insertion/β-OH elimination sequence. This reaction provides a new route to the synthesis of tetrasubstituted olefins.

Full text of DOI:10.1039/c0cc05523a

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COMMUNICATION
Pd-catalyzed coupling of b-hydroxy a-diazocarbonyl compounds with
aryl iodides: a migratory insertion/b-hydroxy elimination sequencew
Lei Zhou, Yizhou Liu, Yan Zhang and Jianbo Wang*
Received 13th December 2010, Accepted 24th January 2011
DOI: 10.1039/c0cc05523a
The coupling of b-hydroxy a-diazocarbonyl compounds with aryl
halides is described, which proceeds through a Pd-catalyzed
migratory insertion/b-OH elimination sequence. This reaction
provides a new route to the synthesis of tetrasubstituted olefins.
palladium-catalyzed processes. As a continuation of our inter-
est in this arena, we are particularly interested in the cases
where there is no b-H available for elimination, such as the
case shown in Scheme 1b. Herein we report that when a b-OH
group is present, the Pd species undergoes b-OH elimination
to form an olefin.
Pd-catalyzed cross-coupling reactions of diazo compounds
have recently emerged as a new type of cross-coupling
reaction.1–6 The reactions presumably proceed through a
migratory insertion process of the Pd carbene intermediates.
The migratory groups have so far included aryl,1 benzyl,2
vinyl,3 allyl,4 and acyl groups.5 In most cases, the palladium
catalyst was regenerated by b-H elimination to form
C(sp2)–C(sp2) bonds (Scheme 1a). We conceived that the
development of a catalytic cycle involving an alternative
terminating step other than b-H elimination would signifi-
cantly expand the application of this methodology in organic
synthesis.
The b-hydroxy a-diazocarbonyl compound 1 can be easily
prepared by nucleophilic addition of ethyl diazo(lithio)acetate
to cyclopentanone.8,9 In the beginning of this investigation, we
studied the coupling of 1 with 4-iodoanisole (eqn (1)) in the
presence of catalytic Pd2(dba)3 and Xphos (2-dicyclohexyl-
phosphino-20,40,60-triisopropyl biphenyl) in THF at 70 1C.
The reaction afforded the non-coupling ring expansion
product 2 and the coupling product a,b-unsaturated ester 3
in 37% and 41% yields, respectively.
In this context, Van Vranken and co-workers have shown
that Z3-allylpalladium intermediates, generated from the
migration of vinyl groups, could be attacked by amine and
carbon nucleophiles.3 The same group also reported a Pd
carbene migratory insertion–carbopalladation sequence in an
intramolecular reaction.6 Very recently, we have developed
a
three-component cross-coupling of N-tosylhydrazones,
terminal alkynes and aryl halides via a sequential palladium
carbene migratory insertion and reductive elimination process.
The reaction forms two separate C–C bonds on the carbenic
carbon.7 These studies have demonstrated the possibility
of combining Pd carbene migratory insertion with other
ð1Þ
The mechanism of this reaction is proposed in Scheme 2.
The oxidative addition of aryl iodides onto a ligated Pd(0)
species generates the arylpalladium(II) complex A, which
dediazotizes the diazo substrate 1 to lead to the formation of
the Pd carbene intermediate B. The migratory insertion of the
aryl group to carbenic carbon gives intermediate C, followed
by the b-OH elimination to afford 3 and releases the Pd(II)
species. Finally, Pd(II) was reduced to Pd(0) in situ to complete
the catalytic cycle.
Scheme 1 A general route to regenerate a palladium catalyst.
The non-coupling ring expansion product 2 is formed by a
metal carbene 1,2-alkyl shift process,10 either from the Pd
carbene B or directly from the diazo substrate 1 catalyzed by
the Pd(0) complex. Initially, we have expected that the ring
expansion product ketone 4 may be formed through a
Pd-promoted 1,2-alkyl shift process.11 However, no trace of
4 could be identified from the reaction mixture, suggesting that
b-OH elimination is a more facile process.
Beijing National Laboratory of Molecular Sciences (BNLMS) and
Key Laboratory of Bioorganic Chemistry and Molecular Engineering
of Ministry of Education, College of Chemistry, Peking University,
Beijing 100871, China. E-mail: wangjb@pku.edu.cn
w Electronic supplementary information (ESI) available: Experimental
procedures, characterization data, 1H and 13C NMR spectra for new
compounds. See DOI: 10.1039/c0cc05523a
c
3622 Chem. Commun., 2011, 47, 3622–3624
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Scheme 2 The proposed reaction mechanism.
A survey of literature indicates that b-OH elimination of a
Pd species is rare.12,13 For example, Jiang et al.13a and Zhu and
Lu13b have reported b-OH elimination with Pd catalysis under
acidic conditions. Both experimental13c and theoretical12a
studies suggest that b-OH elimination is not a facile process
in Pd chemistry. Encouraged by the initial results shown in
eqn (1), we proceeded to study this reaction for improving the
yield of the coupling product 3. Since 1,2-alkyl shift of carbene
is highly sensitive to steric strain, we decided to switch the five-
membered ring of 1 to a six-membered ring. Thus, the
b-hydroxy a-diazo compound 5a was subjected to the
Pd-catalyzed reaction conditions. To our delight, the yield of
the coupling product was improved and the non-coupling ring
expansion product could be largely suppressed (eqn (2)).
Scheme
3
Pd-catalyzed coupling of 4-iodoanisole with various
b-hydroxy a-diazocarbonyl compounds. a If not otherwise noted, the
reaction conditions are as follows: diazo compound (0.3 mmol),
4-iodoanisole (0.5 mmol), Pd2(dba)3 (2.5 mol%), Xphos (10 mol%),
iPr2NH (3 equiv.), THF (3 mL), 70 1C, 24 h. b Isolated yield. c The
reaction was carried out in toluene at 100 1C for 48 h. d E/Z selectivity
was determined by 1H-NMR and GC-MS. eEthyl 3-oxo-2-phenyl-
butanoate was isolated as a major product (57%).
couple with a variety of aryl iodides. As shown in Table 1,
ortho-, para-, and meta-substituted aryl iodides all worked well
in the present system to afford the tetrasubstituted olefin
product in moderate to good yields. Notably, a chloro sub-
stituent at para-position also tolerates the reaction conditions
(entry 8). Besides, 1-iodonaphthalene was suitable for the
reaction, yielding the desired product in 69% (entry 9).
Having demonstrated the scope of aryl iodides, we then
tested the scope of b-hydroxy a-diazocarbonyl compounds by
using 4-iodoanisole as the coupling partner. We are pleased
to find that diazo compounds with substituents on the six-
membered ring were efficiently converted to the corresponding
olefins in moderate yields (Scheme 3). The reaction also
worked with acyclic diazo substrates, however, in these cases
the non-coupling alkyl migratory products were also detected
in addition to the desired products (6n and 6o). The non-
coupling by-products could be suppressed when the reaction
was carried out in toluene at 100 1C with 4 A molecular sieves
as additives. In the case of 5g, only a non-coupling phenyl
migration product was isolated, none of the coupling product
6p could be identified, presumably due to the high migratory
aptitude of the phenyl group in metal carbene.14
ð2Þ
Next, we examined the generality of this reaction by
employing the b-hydroxy a-diazocarbonyl compound 5a to
Table 1 Pd-catalyzed coupling of 5a with various aryl iodidesa
Entry
Ar =
Yieldb (6, %)
1
2
3
4
5
6
7
8
9
10
p-CH3OC6H4
C6H5
6a, 86
6b, 82
6c, 85
6d, 74
6e, 62
6f, 60
6g, 75
6h, 70
6i, 69
6j, 59
p-CH3C6H4
m-CH3C6H4
o-CH3C6H4
o,m-(CH3)2C6H3
p-PhC6H4
p-ClC6H4
1-Naphthyl
o-NO2-p-MeOC6H3
In conclusion, we have reported the Pd-catalyzed cross-coupling
of b-hydroxy a-diazocarbonyl compounds with aryl iodides. The
reaction provides a new method for the synthesis of tetrasubsti-
tuted olefins.15 Mechanistically, the reaction is supposed to involve
a rare case of b-hydroxy elimination of Pd species.
Financial support from National Natural Science Foundation
of China (Grant No. 20902005, 20832002, 21072009, 20821062),
973 Program (No. 2009CB825300), GSK R&D China and China
Postdoctoral Science Foundation is gratefully acknowledged.
a
All the reactions were carried out by using 0.5 mmol of a-hydroxyl
diazo compound 5a, 0.6 mmol of aryl iodides in the presence of
2.5 mol% of Pd2(dba)3, 10 mol% of Xphos and 3 equiv. of iPr2NH in
b
THF (3 mL) at 70 1C for 24 h. Isolated yield.
c
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Chem. Commun., 2011, 47, 3622–3624 3623

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3624 Chem. Commun., 2011, 47, 3622–3624
This journal is The Royal Society of Chemistry 2011