Enol acetal synthesis through carbenoid C-H insertion into tetrahydrofuran catalyzed by CpRu complexes

Article abstract of DOI:10.1002/anie.201201541

Intermolecular C-O instead of C-C bond formation is achieved with [CpRu(CH₃CN)₃][PF₆] and diimine ligands as catalysts of the decomposition of α-diazo-β-ketoesters in THF leading to original products of 1,3C-H insertion (s

Full text of DOI:10.1002/anie.201201541

Angewandte
Chemie
DOI: 10.1002/anie.201201541
ꢀ
C O Coupling
ꢀ
Enol Acetal Synthesis through Carbenoid C H Insertion into
Tetrahydrofuran Catalyzed by CpRu Complexes**
Cecilia Tortoreto, Thierry Achard, Walid Zeghida, Martina Austeri, Laure Guꢀnꢀe, and
Jꢀrꢁme Lacour*
Dedicated to Professor E. Peter Kꢂndig on the occasion of his 65th birthday
Substituted tetrahydrofurans, ubiquitous motifs in biological
and natural product chemistry,[1] are accessible by coupling
reactions of diazoacetates or aryldiazoacetates with simple
a-Diazo-b-ketoesters 1, readily made acceptor/acceptor
reagents,[6] are usually characterized by a better chemical
stability and a moderate reactivity in comparison to other
diazo derivatives.[7] These compounds yet react in the
presence of metal catalysts to form electrophilic carbenoid/
carbene intermediates. These reactive species undergo many
useful transformations, such as cyclopropanation, insertion,
dipolar addition, ylide generation, and
tetrahydrofurans.[2,3] These intermolecular carbenoid C H
ꢀ
insertions[4] are efficiently catalyzed by copper, iridium, iron,
rhodium, and silver salts or complexes.[2,5] Successful asym-
metric versions have also been achieved.[4] In all these
ꢀ
instances, a C C bond is created by insertion of the carbenoid
ꢀ
into a C H bond a to the oxygen ether atom (Scheme 1,
subsequent rearrangement/macrocycli-
zation reactions.[8] Recently, using com-
binations of [CpRu(CH3CN)3][PF6]
([3][PF6])[9] and diimine ligands,[10]
ꢀ
reagents 1 provided selective O H
insertion and condensation reactions
with alcohols, nitriles, ketones, and
aldehydes.[11] This result led us to
examine the reactivity of other Lewis
basic moieties, and THF derivatives in particular, with this
catalytic combination.[12]
Methyl diazoacetoacetate 1a (R1 = R2 = Me, Scheme 1)
was thus added to THF solutions of complex [3][PF6] and
ligands L1 to L10 (Figure 1).[13] Using L1, a moderate heating
to 608C was necessary to induce gas evolution. At that
ꢀ
Scheme 1. Favored enol acetal formation through 1,3 C H insertion of
diazocarbonyl compounds into THF. For ligands L1–L10, see Figure 1.
route b). Herein, in a new development that uses a-diazo-b-
ketoesters 1 as reagents and CpRu (Cp = cyclopentadienyl)
moieties as catalysts, we report the kinetically favored
ꢀ
ꢀ
formation of C O instead of C C bond adducts. The mild
reaction conditions yield novel enol acetal motifs 2 through
ꢀ
unprecedented 1,3 C H insertion reactions (Scheme 1,
route a).
[*] C. Tortoreto, Dr. T. Achard, Dr. W. Zeghida, M. Austeri,
Prof. J. Lacour
Dꢀpartement de Chimie Organique, Universitꢀ de Genꢁve
quai Ernest Ansermet 30, 1211 Genꢁve 4 (Switzerland)
E-mail: jerome.lacour@unige.ch
Homepage: http://www.unige.ch/sciences/chiorg/lacour/
Dr. L. Guꢀnꢀe
Laboratoire de Cristallographie, Universitꢀ de Genꢁve
quai Ernest Ansermet 24, 1211 Genꢁve 4 (Switzerland)
[**] We thank the University of Geneva and the Swiss NSF for financial
support and Stꢀphane Grass for his technical help. We also
acknowledge the contributions of the Sciences Mass Spectrometry
(SMS) platform at the Faculty of Sciences, University of Geneva, and
the help of Dr. S. Michalet in particular.
Figure 1. Ligands L1 to L10, and conversions of 1a (0.5m in THF),
using L and [3][PF6] (2.5 mol% each), after 2 h (corresponds to 95%
conversion for L1) at 608C (1H NMR, 1,3,5-trimethoxybenzene as
internal reference).
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201201541.
Angew. Chem. Int. Ed. 2012, 51, 1 – 6
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
These are not the final page numbers!

.
Angewandte
Communications
Table 2: Substrate scope.[a]
temperature, conversion was complete after 3 h for a rela-
tively high concentration of 1a (0.5m).[14] NMR spectroscopic
analysis of the reaction mixture indicated the formation of
a single product 2a, composed of fragments of 1a and THF.
Entry
R1
R2
Product
Yield[b]
Time [h][c]
1
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Pr
2a
2b
2c
2d
2e
2 f
2g
2h
2i
2j
2k
2l
2m
2n
2o
2p
2q
80
80
63
85
70
89
80
81
60
3
3
2
Et
ꢀ
Its structure was however incompatible with a C C bond
3
4
Ph(CH2)2
PhCH2
15
20
20
24
24
24
24
24
24
24
24
3
forming reaction, and it was different from that of already
1
known 4a (Scheme 1).[15] Based on detailed H, 13C, and IR
5
tBu
6
7
8
9
10
11
12
13
14
15
16[f]
17
Ph
analyses, only an original enol acetal structure involving a
4-ClC6H4
4-NO2C6H4
4-tBuC6H4
4-MeOC6H4
4-CF3C6H4
2-tBuC6H4
PhCH CHCH2
Et
Me
Et
Et
ꢀ
C O linkage was consistent with the data; the motif was
confirmed by X-ray diffraction studies of 2g (see below). Of
=
interest was also that the C C bond of 2a is E-configured.
[d]
–
–
[d]
We then tested the ligands L2 to L10. To our satisfaction,
2a was the single product in all these experiments. The
conversion of 1a was however lower in all instances
(Figure 1).[16] 1,10-Phenanthroline L1 was therefore selected
for the remainder of the study. The results with other
0
15[e]
65
44
27
=
CH2Ph
Ph
CF3
24
24
3
cyclopentadienyl ruthenium(II) salts[17] are summarized in
[d]
–
ꢀ
Table 1. Complexes with large lipophilic counterions (SbF6
,
[a] Reaction conditions: diazo 1 (0.32 mmol), [3][PF6] and L1 (2.5 mol %
each), THF (0.6 mL), 60 8C. [b] Yield of isolated product. [c] Reaction
time at 100% conversion. [d] Decomposition upon chromatography.
[e] Intramolecular cyclopropanation adduct (65%) as major component.
Table 1: Metal complex selection.[a]
Entry
[Ru]
Anion
Conv.[b]
1
[f] Incomplete reaction. Conversion not measurable by H NMR spec-
1
2
3
4
5
6
CpRu(CH3CN)3
CpRu(CH3CN)3
CpRu(CH3CN)3
CpRu(CH3CN)3
CpRu(CH3CN)3
Cp*Ru(CH3CN)3
PF6
SbF6
TRISPHAT
TRISPHAT-N
OTf
95
95
80
43
30
90
troscopy.
PF6
[a] Reaction conditions: diazo 1a (0.32 mmol), [Ru] and L1 (2.5 mol %
each), THF (0.6 mL), 2 h, 60 8C. [b] Conversion of 1a (1H NMR, 1,3,5-
trimethoxybenzene as internal reference).
TRISPHAT (= P(O2C6Cl4)3 ))[18] had a reactivity similar to
ꢀ
Figure 2. ORTEP view of the structure of (E)-2g in the crystal. Thermal
that of [3][PF6]. Lower conversions were however noticed
with anions able to coordinate at the metal center (OTf,
TRISPHAT-N).[19] Complex [Cp*Ru(CH3CN)3][PF6] (Cp* =
pentamethylcyclopentadienyl)[20] was also effective, but the
reaction was accompanied by concurrent polymerization of
THF. Complex [3][PF6] was therefore used in all further
experiments.
ellipsoids are drawn at 50% probability level.
1
2
=
(R = PhCH CHCH2, R = Me), was also tested. In this
case, the product of intramolecular cyclopropanation (65%)
predominated and the corresponding enol acetal 2m was
isolated in 15% yield only (Table 2, entry 13).[23]
To investigate the scope of the reaction, substrates with
different ester groups (alkyl, aryl, allyl) were tested and
reactions were allowed to run until full conversion (Table 2).
With bulkier alkyl esters, moderate to good yields of 2 were
afforded after prolonged reaction time (Table 2, entries 2–
5).[21] A series of aryl esters was also studied (Table 2,
entries 6–12). In essentially all cases, products of type 2
were obtained. After 24 h, complete conversions were
achieved with reagents carrying either electron-donating or
electron-withdrawing substituents at the para position; this
indicates a global lack of electronic effects. Only the highly
hindered o-tert-butylphenyl reagent did not lead to any
insertion reaction (Table 2, entry 12).[22] Product 2g was
found to be moderately soluble in a 4:1 mixture of hexane
and Et2O, which made X-ray-quality crystals accessible. The
result of the X-ray analysis is shown in Figure 2. For
compounds 2j and 2k, although predominant in the crude
mixtures, decomposition occurred upon chromatographic
purification (on SiO2 or Al2O3). Another substrate, 1m
Next, the ketone substituent was varied. For the propyl
substituent (1n), a similar reactivity was observed (3 h, 65%).
With benzyl and phenyl substituents, reactions were slower,
indicative of a relatively strong steric effect (2o and 2p,
Table 2). In the case of 1q (R2 = CF3), the reaction was fast
(3 h); the corresponding product 2q however decomposed
upon chromatography.[24]
With 2-methyltetrahydrofuran (5) instead of THF, one
equivalent was used as the reaction proceeded well in CH2Cl2
as solvent [Eq.(1)]. A longer reaction time was necessary
(24 h instead of 3 h), but the isolation of the products (6a and
2
www.angewandte.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 1 – 6
These are not the final page numbers!

Angewandte
Chemie
6b) was easier than for reactions performed with 5 as solvent.
ꢀ
The C O bond formation occurred only on the secondary
CH2 carbon atom; no evidence was found in the crude
mixture for an insertion on the more hindered tertiary CH
site.[25] In line with previous studies, this regioselectivity can
be rationalized on steric grounds.[2b] Compounds 6a and 6b
are obtained as 3.3:1 mixtures of diastereomers due to a lack
of discrimination at the anomeric carbon atom.
To gain some insight into the nature of the transformation,
a series of experiments was performed using reagents 1a, 1 f,
and 1h in 1:1 mixtures of THF and [D8]THF [Eq. (2)]. Mass
spectrometry indicated the predominant formation of homo-
coupling products HH and DD (> 90%) over cross-coupling
products HD and DH (< 10%).[26] A larger proportion of HH
over DD was also denoted (Table 3).
_
Scheme 2. Mechanistic rationale.NN corresponds to 1,10-phenatroline
(L1).
Table 3: Homocoupling and kinetic isotope effects.
Finally, with compounds 2 in hand, we were able to also
Entry
R1
Product[a]
Ratio HH/DD[b]
ꢀ
synthesize the products of “classical” C C bond formation.
Based on literature precedents,[30] we expected that the enol
fragment of 2 would behave as a good leaving group in the
presence of Lewis acids. After an induced dissociation,
a recombination within the oxocarbenium/enolate ion pair
would form adducts 4. This assumption was validated in the
transformation of 2a into 4a using catalytic amounts of
Cu(OTf)2 or TMSOTf (5 mol%, Scheme 3).[31,32] By using
1
2
3
Me
Ph
4-NO2C6H4
2a
2 f
2h
3.0:1.0
3.3:1.0
3.4:1.0
[a] Reaction conditions: diazo 1 (0.32 mmol), [3][PF6] and L1
(2.5 mol %), 1:1 THF:[D8]THF (0.6 mL), 60 8C. [b] Measured by
400 MHz 1H NMR spectroscopy and confirmed by ESI mass spectrom-
etry.
The predominant formation of the homocoupling prod-
ucts HH and DD advocates for a concerted hydrogen transfer
mechanism. The higher proportion of HH over DD indicates
the occurrence of a primary kinetic isotope effect.[27] The
measured kH/kD values, from 3.0 to 3.4, are in accordance with
ꢀ
previously reported results for C C bond forming reac-
tions.[2b] A mechanistic rationale coherent with these results is
proposed in Scheme 2.[28]
In detail, catalyst precursor [3][PF6] reacts with L1 to
generate a [Cp(L1)(CH3CN)2Ru][PF6] species, which, upon
dissociation of the monodentate ligand, forms the catalyti-
cally active 16-electron complex A.[10] This electron-deficient
entity probably reacts with diazo reagent 1 to afford metal
carbenoid intermediate B. At this stage, in contrast to classical
Scheme 3. a) [3][PF6] (2.5 mol%), L1 (2.5 mol%), THF, 608C, 3 h;
b) TMSOTf or Cu2(OTf)2 (5 mol%), CH2Cl2, 0!258C, 1 h; c) [3][PF6]
(2.5 mol%), L1 (2.5 mol%), THF (1 equiv), CH2Cl2, 608C, 24 h.
ꢀ
only one equivalent of THF, the C H insertion and rear-
ꢀ
C H insertions, which proceed via 3-membered transition
rangement steps can be combined into a single-pot process. In
this tandem fashion, a higher yield of 4a was obtained (90 vs.
72% for two steps).
states,[7] a concerted reaction occurs that involves the keto
ꢀ
group of carbenoid B and the more accessible Ca H bond of
the ether moiety.[29] A concomitant formation of the novel C
Using 1,3-dioxolane instead of THF as reactive ether, the
ꢀ
ꢀ
ꢀ
O and C H bonds occurs in a 5-membered transition state
classical C C bond formation occurs under thermal condi-
TS° to release both product 2 and catalyst A. This step is
stereo-determining as the s-cis conformation of the carbonyl
group in intermediate B is conserved to form the E-
configured enol.
tions (Scheme 4). At 608C, decomposition of 1b in the
presence of the acetal affords 8 as the single adduct. The
ꢀ
product of C O bond forming reaction, 7, is however
observed after 1 hour at 258C. Two hours at 608C are then
sufficient to induce the rearrangement into 8, and this without
Angew. Chem. Int. Ed. 2012, 51, 1 – 6
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
3
These are not the final page numbers!

.
Angewandte
Communications
Minisci, Y. M. Yan, L. H. Zhao, Tetrahedron Lett. 1993, 34,
2517 – 2520; e) A. J. Clark, S. Rooke, T. J. Sparey, P. C. Taylor,
Tetrahedron Lett. 1996, 37, 909 – 912; f) J. C. Gong, P. L. Fuchs, J.
Am. Chem. Soc. 1996, 118, 4486 – 4487; g) J. S. Xiang, A.
Mahadevan, P. L. Fuchs, J. Am. Chem. Soc. 1996, 118, 4284 –
4290; h) J. Xiang, W. L. Jiang, J. C. Gong, P. L. Fuchs, J. Am.
Chem. Soc. 1997, 119, 4123 – 4129; i) A. Inoue, H. Shinokubo, K.
Oshima, Synlett 1999, 1582 – 1584; j) S. Kim, N. Kim, W. J.
Chung, C. H. Cho, Synlett 2001, 937 – 940; k) K. Hirano, S.
Sakaguchi, Y. Ishii, Tetrahedron Lett. 2002, 43, 3617 – 3620; l) H.
Inoue, Y. Nagaoka, M. Tomioka, J. Org. Chem. 2002, 67, 5864 –
5867; m) K. Yamada, H. Fujihara, Y. Yamamoto, Y. Miwa, T.
Taga, K. Tomioka, Org. Lett. 2002, 4, 3509 – 3511; n) T.
Yoshimitsu, Y. Arano, H. Nagaoka, J. Org. Chem. 2003, 68,
625 – 627; o) P. P. Singh, S. Gudup, S. Ambala, U. Singh, S.
Dadhwal, B. Singh, S. D. Sawant, R. A. Vishwakarma, Chem.
Commun. 2011, 47, 5852 – 5854.
Scheme 4. [3][PF6] (2.5 mol%), L1 (2.5 mol%), 1,3-dioxolane (solvent):
a) 608C, 3 h; b) 258C, 1 h; c) 608C, 2 h.
ꢀ
any added Lewis acid. This result indicates that C O bond
ꢀ
forming is kinetically preferred over C C bond forming using
the current catalyst combination.
[4] a) M. P. Doyle, R. Duffy, M. Ratnikov, L. Zhou, Chem. Rev.
2010, 110, 704 – 724; b) H. M. L. Davies, D. Morton, Chem. Soc.
Rev. 2011, 40, 1857 – 1869; c) S. Y. Zhang, F. M. Zhang, Y. Q. Tu,
Chem. Soc. Rev. 2011, 40, 1937 – 1949.
[5] a) H. M. L. Davies, T. Hansen, D. W. Hopper, S. A. Panaro, J.
Am. Chem. Soc. 1999, 121, 6509 – 6510; b) J. M. Fraile, J. I.
Garcia, J. A. Mayoral, M. Roldan, Org. Lett. 2007, 9, 731 – 733;
c) H. M. Mbuvi, L. K. Woo, Organometallics 2008, 27, 637 – 645;
d) H. Suematsu, T. Katsuki, J. Am. Chem. Soc. 2009, 131, 14218 –
14219; e) C. J. Lovely, J. A. Flores, X. F. Meng, H. V. R. Dias,
Synlett 2009, 129 – 132; f) J. M. Fraile, J. A. Mayoral, N. Ravasio,
M. Roldan, L. Sordelli, F. Zaccheria, J. Catal. 2011, 281, 273 –
278.
[6] Diazo reagents of type 1 are readily prepared by using diazo-
transfer reagents such as p-acetamidobenzenesulfonyl azide (p-
ABSA): a) G. Maas, Angew. Chem. 2009, 121, 8332 – 8341;
Angew. Chem. Int. Ed. 2009, 48, 8186 – 8195; see also b) W. J.
Brehm, T. Levenson, J. Am. Chem. Soc. 1954, 76, 5389 – 5391;
c) D. F. Taber, R. E. Ruckle, J. Am. Chem. Soc. 1986, 108, 7686 –
7693; d) J. S. Baum, D. A. Shook, H. M. L. Davies, H. D. Smith,
Synth. Commun. 1987, 17, 1709 – 1716; e) M. Hrytsak, T. Durst,
J. Chem. Soc. Chem. Commun. 1987, 1150 – 1151; f) M. P. Doyle,
L. J. Westrum, W. N. E. Wolthuis, M. M. See, W. P. Boone, V.
Bagheri, M. M. Pearson, J. Am. Chem. Soc. 1993, 115, 958 – 964;
g) J. R. Davies, P. D. Kane, C. J. Moody, Tetrahedron 2004, 60,
3967 – 3977; h) A. M. Harned, W. M. Sherrill, D. L. Flynn, P. R.
Hanson, Tetrahedron 2005, 61, 12093 – 12099; i) M. E. Meyer,
E. M. Ferreira, B. M. Stoltz, Chem. Commun. 2006, 1316 – 1318;
j) K. M. Allan, B. D. Hong, B. M. Stoltz, Org. Biomol. Chem.
2009, 7, 4960 – 4964; k) J. L. Chiara, J. R. Suarez, Adv. Synth.
Catal. 2011, 353, 575 – 579.
In conclusion, we have reported a new reactivity in the
CpRu-catalyzed decomposition of diazo compounds and, as
a consequence, a novel functionalization of tetrahydrofurans.
To our knowledge, it is the first one-step synthesis of enol
ꢀ
acetal moieties by direct C H activation.
Experimental Section
Representative procedure: In a 2 mL screw-cap vial equipped with
a magnetic stirring bar, L1 (1.5 mg, 8 mmol, 2.5 mol%) and [CpRu-
(CH3CN)3][PF6] (3.5 mg, 8 mmol, 2.5 mol%) were dissolved in
0.60 mL of dry THF. The vial was flushed with argon and capped.
The resulting deep red solution was stirred for 20 min at 258C and
then diazoketoester 1 (0.32 mmol) was added. The solution was
stirred at 608C until full conversion (1H NMR monitoring). The crude
mixture was purified by column chromatography (Hexane/Et2O,
SiO2) to afford insertion product 2.
Crystal structure analysis of 2g: CCDC 867253 contains the
supplementary crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
Received: February 24, 2012
Published online: && &&, &&&&
ꢀ
ꢀ
Keywords: C H insertion · C O coupling · diazo compounds ·
enol acetals · tetrahydrofurans
.
[7] M. P. Doyle, M. A. McKervey, T. Ye, Modern Catalytic Methods
for Organic Synthesis with Diazo Compounds: From Cyclo-
propanes to Ylides, Wiley, New York, 1998.
[1] a) Polyether Antibiotics: Naturally Occurring Acid Ionophores
(Ed.: J. W. Westley), Marcel Dekker, New York, 1982; b) D. E.
Levy, C. Tang, The Chemistry of C-Glycosides, 1st ed., Perga-
mon, Oxford, 1995; c) F. Q. Alali, X. X. Liu, J. L. McLaughlin, J.
Nat. Prod. 1999, 62, 504 – 540; d) M. M. Faul, B. E. Huff, Chem.
Rev. 2000, 100, 2407 – 2473; e) E. J. Kang, E. Lee, Chem. Rev.
2005, 105, 4348 – 4378; f) M. Saleem, H. J. Kim, M. S. Ali, Y. S.
Lee, Nat. Prod. Rep. 2005, 22, 696 – 716.
[2] a) H. M. L. Davies, T. Hansen, J. Am. Chem. Soc. 1997, 119,
9075 – 9076; b) H. M. L. Davies, T. Hansen, M. R. Churchill, J.
Am. Chem. Soc. 2000, 122, 3063 – 3070; c) M. Mar Diaz-
Requejo, T. R. Belderrain, M. C. Nicasio, S. Trofimenko, P. J.
Pꢀrez, J. Am. Chem. Soc. 2002, 124, 896 – 897.
[3] a-Functionalization of THF derivatives is also feasible through
free-radical and other metal-catalyzed processes: a) G. A. Rus-
sell, P. Ngoviwatchai, J. Org. Chem. 1989, 54, 1836 – 1842; b) V.
Gevorgyan, E. Priede, E. Liepins, M. Gavars, E. Lukevics, J.
Organomet. Chem. 1990, 393, 333 – 338; c) D. P. Matthews, J. R.
McCarthy, J. Org. Chem. 1990, 55, 2973 – 2975; d) F. Fontana, F.
[8] a) A. Padwa, M. D. Weingarten, Chem. Rev. 1996, 96, 223 – 269;
b) M. P. Doyle, D. C. Forbes, Chem. Rev. 1998, 98, 911 – 935;
c) H. M. L. Davies, R. E. J. Beckwith, Chem. Rev. 2003, 103,
2861 – 2903; d) Z. H. Zhang, J. B. Wang, Tetrahedron 2008, 64,
6577 – 6605; e) W. Zeghida, C. Besnard, J. Lacour, Angew. Chem.
2010, 122, 7411 – 7414; Angew. Chem. Int. Ed. 2010, 49, 7253 –
7256; f) D. Rix, R. Ballesteros-Garrido, W. Zeghida, C. Besnard,
J. Lacour, Angew. Chem. 2011, 123, 7446 – 7449; Angew. Chem.
Int. Ed. 2011, 50, 7308 – 7311.
[9] a) B. M. Trost, F. D. Toste, A. B. Pinkerton, Chem. Rev. 2001,
101, 2067 – 2096; b) E. P. Kꢁndig, F. R. Monnier, Adv. Synth.
Catal. 2004, 346, 901 – 904; c) A. Mercier, W. C. Yeo, J. Y. Chou,
P. D. Chaudhuri, G. Bernardinelli, E. P. Kꢁndig, Chem.
Commun. 2009, 5227 – 5229.
[10] J. L. Renaud, C. Bruneau, B. Demerseman, Synlett 2003, 408 –
410.
4
www.angewandte.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 1 – 6
These are not the final page numbers!

Angewandte
Chemie
[11] M. Austeri, D. Rix, W. Zeghida, J. Lacour, Org. Lett. 2011, 13,
1394 – 1397.
2007, 26, 2141 – 2143; b) S. Constant, S. Tortoioli, J. Mꢁller, D.
Linder, F. Buron, J. Lacour, Angew. Chem. 2007, 119, 9137 –
9140; Angew. Chem. Int. Ed. 2007, 46, 8979 – 8982.
[12] CpRu complexes with cyclooctadiene and diphosphine ligands,
known to catalyze the decomposition of certain diazo deriva-
tives, were unreactive in the titled chemistry: W. Baratta, A.
DelZotto, P. Rigo, Chem. Commun. 1997, 2163 – 2164; W.
Baratta, W. A. Herrman, R. M. Kratzer, P. Rigo, Organometal-
lics 2000, 19, 3664 – 3669; M. Basato, C. Tubaro, A. Biffis, M.
Bonato, G. Buscemi, F. Lighezzolo, P. Lunardi, C. Vianini, F.
Benetollo, A. Del Zotto, Chem. Eur. J. 2009, 15, 1516 – 1526.
[13] The Supporting Information contains optimization studies with
L1 and conversion results with less-performing and even
inhibiting ligands.
[20] M. D. Mbaye, B. Demerseman, J. L. Renaud, L. Toupet, C.
Bruneau, Angew. Chem. 2003, 115, 5220 – 5222; Angew. Chem.
Int. Ed. 2003, 42, 5066 – 5068.
[21] Moderate yields are often due to the volatility of the compounds.
[22] After 48 h, only 25% conversion of 1l into the dimer product
was observed.
[23] W. Lin, A. B. Charette, Adv. Synth. Catal. 2005, 347, 1547 – 1552.
[24] Due to the presence of the electron-withdrawing CF3 group, the
leaving-group ability of the enol fragment is strongly increased
ꢀ
leading to a probably rapid hydrolysis of the C O bond during
purification.
[14] Without ligand, only 12% conversion is observed and polymer-
ization of THF occurs.
ꢀ
[25] Preferential C H insertion on the tertiary carbon atom could be
[15] Compound 2a is characterized by 1H NMR signals at 5.66 (d, J =
expected based on electronic grounds.
=
4 Hz, OCHO) and 5.32 (s, C CH) ppm that are at quite higher
[26] The minimal amounts of products with M + 1 and M + 7 masses
might be due to the formation of the corresponding cross-
coupling products of type 4 according to a dissociation/reasso-
ciation mechanism.
[27] M. Gꢂmez-Gallego, M. A. Sierra, Chem. Rev. 2011, 111, 4857 –
4963.
[28] An alternative hydride abstraction mechanism can be consid-
ered: H. T. Bonge, T. Hansen, Eur. J. Org. Chem. 2010, 4355 –
4359.
frequency than the most deshielded proton of 4a (m, d =
4.43 ppm). The configuration of the double bond is readily
determined by a NOESY experiment; see: R. Bihovsky, M. U.
Kumar, S. Ding, A. Goyal, J. Org. Chem. 1989, 54, 4291 – 4293;
O. Moriya, Y. Urata, Y. Ikeda, Y. Ueno, T. Endo, J. Org. Chem.
1986, 51, 4708 – 4709.
[16] With enantiopure ligands L7, L9, and L10 no enantioselectivity
was observed.
[17] Other metal sources were also tested. Whereas copper salts did
not induce the formation of 2a, a small amount (10%) of 2a is
observed in the reaction catalyzed by [Rh2(OAc)4]. Interestingly,
[29] C. ꢃzen, N. S. Tꢁzꢁn, Organometallics 2008, 27, 4600 – 4610.
[30] a) D. J. Dixon, S. V. Ley, E. W. Tate, J. Chem. Soc. Perkin Trans.
1 1999, 2665 – 2667; b) M. F. Buffet, D. J. Dixon, G. L. Edwards,
S. V. Ley, E. W. Tate, J. Chem. Soc. Perkin Trans. 1 2000, 1815 –
1827; c) D. J. Dixon, S. V. Ley, E. W. Tate, J. Chem. Soc. Perkin
Trans. 1 2000, 2385 – 2394.
[31] Product 4a is highly volatile and hence the yield of 90%
corresponds to a quantitative reaction.
[32] Compound 6a also rearranges under these Lewis acidic con-
ditions, but the reaction generates a complex mixture of
diastereomers that was not deconvoluted.
this RhII complex does not promote the C O to C C rearrange-
ment detailed in Scheme 3.
ꢀ
ꢀ
[18] a) J. Lacour, C. Ginglinger, C. Grivet, G. Bernardinelli, Angew.
Chem. 1997, 109, 660 – 662; Angew. Chem. Int. Ed. Engl. 1997,
36, 608 – 610; b) J. Lacour, D. Moraleda, Chem. Commun. 2009,
7073 – 7089; c) L. Hintermann, L. Xiao, A. L. Labonne, U.
Englert, Organometallics 2009, 28, 5739 – 5748.
[19] a) For the chemical structure of TRISPHAT-N, see: S. Constant,
R. Frantz, J. Mꢁller, G. Bernardinelli, J. Lacour, Organometallics
Angew. Chem. Int. Ed. 2012, 51, 1 – 6
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!

.
Angewandte
Communications
Communications
ꢀ
C O Coupling
C. Tortoreto, T. Achard, W. Zeghida,
M. Austeri, L. Guꢁnꢁe,
J. Lacour*
&&&& — &&&&
ꢀ
ꢀ
Enol Acetal Synthesis through Carbenoid
Intermolecular C O instead of C C bond
formation is achieved with [CpRu-
diazo-b-ketoesters in THF leading to
ꢀ
ꢀ
C H Insertion into Tetrahydrofuran
original products of 1,3 C H insertion
Catalyzed by CpRu Complexes
(CH3CN)3][PF6] and diimine ligands as
catalysts of the decomposition of a-
(see scheme).
6
www.angewandte.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 1 – 6
These are not the final page numbers!