Pd-catalyzed asymmetric synthesis of N-allenyl amides and their Au-catalyzed cycloisomerizative hydroalkylation: A new route toward enantioenriched pyrrolidones

Article abstract of DOI:10.1002/chem.201103902

Palladium to make them, gold to cyclize them! Gold-catalyzed cycloisomerizative hydroalkylation of N-allenyl amides affords regioselectively 4-vinyl-γ-lactams. This transformation is stereospecific and takes place with a total axis-to-center chirality tra

Full text of DOI:10.1002/chem.201103902

DOI: 10.1002/chem.201103902
Pd-Catalyzed Asymmetric Synthesis of N-Allenyl Amides and Their Au-
Catalyzed Cycloisomerizative Hydroalkylation: A New Route Toward
Enantioenriched Pyrrolidones
Audrey Boutier,[a] Claire Kammerer-Pentier,[a] Norbert Krause,[b]
Guillaume Prestat,*[a] and Giovanni Poli*[a]
Dedicated to Professor Cesare Gennari on the occasion of his 60th birthday
Over the past decade, much attention has been devoted
to gold catalysis for the synthesis of heterocycles through
carbon–carbon and carbon–heteroatom bond formation.[1]
Indeed, AuI and AuIII complexes are carbophilic Lewis acids
that are able to activate unsaturated carbon–carbon bonds
towards nucleophilic attack. However, gold-catalyzed hydro-
alkylations involving an activated methylene function have
only been rarely studied,[2] and, to the best of our knowl-
edge, only two examples have so far involved intramolecular
gold-catalyzed allene hydroalkylations.[3]
Our ongoing research is focused on the development of
new atom economical methodologies for the synthesis of
Scheme 1. Synthesis of 4-vinyl-g-lactams: comparison between the old
palladium-catalyzed strategies and the new gold-catalyzed one.
heterocyclic structures.[4] We thus envisioned that a gold-cat-
alyzed intramolecular hydroalkylation of N-allenyl amides
bearing an active methylene might allow to access 4-vinyl-g-
lactams. Such a full atom-economical process (Scheme 1,
left) would represent a valuable alternative to the palladi-
um-catalyzed intramolecular alkylation of the corresponding
N-(4-acetoxy)allylamides (Scheme 1, top right),[4a] or to the
palladium-catalyzed allene carbopalladation/allylation of N-
allenyl amides (Scheme 1, bottom right),[4i] previously re-
ported by some of us.
Herein we report our results on the gold-catalyzed cyclo-
ACHTUNGTRENNUNGisomerisation reaction of N-allenyl amides leading to the
corresponding 4-vinyl-g-lactams. We also demonstrate that
a clean axial-to-central chirality transfer occurs when start-
ing from a stereogenic allene moiety. Furthermore, the prep-
aration of the requisite enantioenriched allenyl b-ketoamide
was achieved by means of an original palladium-catalyzed
allenylic amination reaction.
N-Allenyl b-ketoamide 1a[5] was chosen as our model sub-
strate to test the cycloisomerization. After a preliminary
screening of catalysts[6] (AuBr3, AuCl, Au(OH)3, [PdCl2-
ACHNUTTGREG(NNUN CH3CN)2], [PdCAHUTTGNRENNUG(CH3CN)4]ACHTNUGRETGUN[NN BF4]2, [PdCAHTNUGTERN(NUGN OCOCF3)2]), addi-
tives (nBu4NI, AgOTf), solvents (CH2Cl2, toluene, hexane,
cyclohexane, THF), bases (EtONa, DBU, nBu4NOH, KOH,
no base), and temperature for this reaction, the following
optimal conditions were established: AuBr3 (5 mol%),
nBu4NOH (2.0 equiv), cyclohexane, reflux. Under such con-
ditions the desired lactam 2a was produced regio- and ste-
reoselectively in 80% yield (Scheme 2).
[a] A. Boutier, Dr. C. Kammerer-Pentier, Prof. Dr. G. Prestat,
Prof. Dr. G. Poli
Institut Parisien de Chimie Molꢀculaire UMR CNRS 7201
FR2769 Institut de Chimie Molꢀculaire
UPMC Univ Paris 06
4, Place Jussieu, case 183, 75005, Paris (France)
Fax : (+33)144274287
E-mail: guillaume.prestat@upmc.fr
giovanni.poli@upmc.fr
Scheme 2. Cycloisomerization of the model N-allenyl b-ketoamide 1a.
[b] Prof. Dr. N. Krause
Organic Chemistry, Dortmund University of Technology
Otto-Hahn-Strasse 6, 41227 Dortmund (Germany)
Fax : (+49)231-755-3884
With the optimized reaction conditions in hand, the scope
of the hydroalkylation was examined on a 0.5 mmol scale,
using various allenyl b-ketoamide precursors (Scheme 3).
The monosubstituted allene 1b afforded g-lactam 2b in
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201103902.
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Chem. Eur. J. 2012, 18, 3840 – 3844

COMMUNICATION
cleavage of the CF3CO moiety might render this amide an
ideal nucleophile for our purpose.
The asymmetric conversion of racemic allenyl acetate
(ꢀ)-3 into allenyl trifluoroacetamide 5 f was thus investigat-
ed (Table 1). Preliminary tests indicated no reactivity in the
Table 1. Search for the best chiral ligand.[a,b]
Entry
Ligand
t [h]
T [8C]
Yield [%]
e.r.[c]
1
2
3
4
5
6
7
8
9
L2
L3
L4
L5
L6
L7
L8
L9
L10
L11
6
4
24
16
4
25
25
55
55
25
25
25
25
25
25
87
79
8
43
96
92
64
68
49
75
21:79
47:53
50:50
32:68
51:49
50:50
14:86
86:14
87:13
17:83
3
24
24
24
24
Scheme 3. Scope of the hydroalkylation reaction (all reactions were run
on a 0.5 mmol scale. Yields refer to isolated yields). a) Only the trans
isomer was observed. b) 75:25 diastereoisomeric mixture.
10
[a] For the structures of the chiral ligands see the Supporting Informa-
tion. [b] No reaction was observed when using ligand L1. [c] e.r.’s deter-
mined by chiral HPLC SFC (AD-H, CO2/iPrOH 90:10, 2.5 mLminꢁ1
,
85 bar).
a moderate yield (58%). As the same lactam 2b had been
previously obtained by us by means of a Pd0-catalyzed ally-
lation process, the stereochemistry was unambiguously as-
signed as the trans configuration between the newly formed
stereocenters.[4a,7] The cyclohexyl-substituted precursor 1c
reacted smoothly to afford the desired lactam 2c in 71%
yield. The replacement of the acetyl group by the bulkier
pivaloyl group was also well tolerated, leading to pyrroli-
done 2d in 69% yield. Precursors bearing a stereogenic al-
lenyl moiety, such as 1e and 1 f afforded the (E)-alkene cyc-
lization products 2e and 2 f in good (72%) to excellent
(90%) yields, respectively.[8] The allyl-substituted allenyl b-
ketoamide 1aa could also be cyclized to the corresponding
pyrrolidone 2aa bearing a quaternary carbon atom, al-
though in a rather moderate yield (34%). Unfortunately, re-
lated substrates bearing electron-withdrawing groups other
than a ketone (MeO2C-, NC-, PhSO2-) failed to cyclize.
The observation that the chiral racemic allenic precursors
1e and 1 f led to single trans-(E)-diastereomers suggested
that the transformation might be stereospecific. This would
imply that starting from an enantioenriched substrate, axial-
to-central chirality transfer should be at work. Therefore,
we decided to test the cyclization of an enantioenriched
sample of 1 f. For this purpose, we planned to synthesize the
parent N-allenyl amine by an asymmetric palladium-cata-
lyzed amination of the corresponding racemic N-allenyl ace-
tate. Such type of asymmetric transformation has already
two precedents in the literature.[9] However, the reported
methods were mainly developed for the synthesis of tertiary
allenyl amines. As our synthetic plan required the use of
a secondary N-allenyl amine, we selected N-benzyl trifluor-
oacetamide (4) as the nucleophile. Indeed, we reasoned that
its easy deprotonation together with the smooth hydrolytic
presence of the Trost standard ligand L1,[10] whereas promis-
ing results were obtained with (R)-BINAP (L2; BINAP=
2,2’-bis(diphenylphosphino)-1,1’-binaphthyl).
A
careful
screening with this ligand involving reaction temperature,
palladium source, base, solvent, and additives as parameters
allowed to retain the following conditions: [NaH, [Pd2-
AHCTUNTGRENGUN(N dba)3]·CHCl3 (dba=dibenzylideneacetone; 2.5 mol%),
(R)-BINAP (7.5 mol%), LiCl (20 mol%), THF, RT.[11] Sub-
sequent use of these optimized reaction conditions in the
presence of (S,S)-DIOP (L3),[12] (S,S)-CHIRAPHOS (L4),[13]
(S)-tBu-PHOX (L5),[14] SL-W001-1 (L6),[15] SL-J005-
1 (L7),[16] (R)-SYNPHOS (L8),[17] (S)-MeOBIPHEP (L9),[18]
(S)-3,5-tBuMeOBIPHEP (L10),[19] and (R)-3,5-tBu-4-MeO-
MeOBIPHEP (L11)[19] indicated the atropoisomeric ligands
L2 (Table 1, entry 1) and L9 (Table 1, entry 8) as the ligands
of choice.
Further experiments[20] showed that the product isolated
after partial conversion possessed the same enantiomeric
ratio (e.r.)[21] (22:78) as that isolated after total substrate
conversion. Furthermore, the unreacted substrate recovered
from the above experiment was found to be enantioenriched
(e.r. 71:29) and its resubmission to the same reaction condi-
tions until full conversion, gave the final amide (ꢁ)-5 f,
again in 21:79 e.r.[21] (61% yield). This result clearly rules
out a static kinetic resolution phenomenon and points to
a dynamic kinetic asymmetric resolution (DYKAT)[22] with-
out the involvement of a memory effect.[23] Finally, resub-
mission of a racemic sample of the allenyl trifluoroaceta-
mide 5 to the asymmetric amination conditions, gave back,
as expected, the unchanged racemic material, thereby con-
ꢁ
firming the irreversibility of the N C bond-formation step.
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3841

G. Poli, G. Prestat et al.
Each enantiomer of 3 is expected to undergo pre-com-
plexation to the catalytic system [Pd0(L*)] anti to the alkyl
substituent, to reversibly[24] form a diastereomeric couple of
vinylidene-allyl h3-complexes Sa,Sp-A[25] and Ra,Rp-A, which
can rapidly equilibrate via the h1-dienyl intermediate B
(Scheme 4). Eventually, the irreversible rate- and enantio-
The allylic amination in the presence of the best perform-
ing ligand L9, was then repeated on a 2.0 mmol scale, ob-
taining allenamide (+)-5 f in 79% yield and 82:18 e.r.
(Scheme 5).
Scheme 5. Asymmetric amination of rac-3 and chirality transfer experi-
ment.
Scheme 4. Mechanistic proposal for the palladium-catalyzed DYKAT
process (ꢀ)-3!5 using L9 (or ent-L2) as ligand. Indexes a and p specify
the axial and the planar chirality descriptors, respectively.
Treatment of the latter with K2CO3 in MeOH/H2O 10/1 at
508C led to N-benzyl-(non-2,3-dien-1-yl)-1-amine ((+)-6 f)
in 87% yield. Acylation of this amine with 2,2,6-trimethyl-
4H-1,3-dioxin-4-one afforded the enantioenriched N-allenyl
b-ketoamide (+)-1 f in 85% yield. Finally, treatment of
(+)-1 f under the previously optimized gold-catalyzed cyclo-
discriminating addition of the amide enantioselectively gen-
erates the allenyl amides 5. It is worth noting that although
consumption of the enantiomeric substrates takes place at
unequal rates (see the above experiment at partial substrate
conversion), no correlation can exist between this initial ki-
netic resolution and the sense of the final asymmetric induc-
tion, which solely depends on the energy difference (ca.
3.8 kJ)[26] between the diastereomeric transition states of the
AHCTUNGTREGiNNUN somerization conditions produced the expected pyrrolidone
(+)-2 f in 85% yield and 81:19 e.r..[21] As the enantiomeric
ratios of (+)-1 f and of (+)-2 f are virtually identical, the ste-
reospecificity of the axial-to-central chirality transfer of the
hydroalkylation process is proved.
ꢁ
final N C bond-forming step. The ensemble of the above in-
formation allows proposing a mechanism as well as some
qualitative considerations.
Absolute configuration[11] was established by comparison
of the experimental circular dichroism spectra of (+)-1 f and
(+)-2 f with those simulated from DFT calculations and ac-
cordingly, a proposed mechanism for the process is shown in
Scheme 6.[27,28] Reversible gold complexation on (+)-1 f may
It is also worth noting that the relative energy differences
between the barriers to interconversion in the equilibrating
steps, (internal barriers as depicted in Figure 1) do not
govern the enantioselectivity of the process (Curtin–Ham-
mett conditions), as long as kepi >kS >kR.
Figure 1. Qualitative energetic profile of the Pd-catalyzed DYKAT pro-
cess (ꢀ)-3!5 using L9 (or ent-L2). Comparison between two arbitrarily
selected manifolds indicates the absence of correlation between the sense
of the asymmetric induction observed in the products and the initial ki-
netic resolution of the starting racemic substrate.
Scheme 6. Mechanistic proposal for the gold-catalyzed hydroalkylation
reaction.
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Chem. Eur. J. 2012, 18, 3840 – 3844

Dynamic Kinetic Asymmetric Transformation
COMMUNICATION
occur on both unsaturated sites and on both faces of the al-
lenyl moiety. However, only coordination of the internal
double bond from the same side as the pentyl group leads
to the reactive intermediate C. The anti-to-Au enolate addi-
tion[29] appears unconstrained and generates the vinylgold
complex D via transition state E. This event has to be com-
pared with the alternative anti-to-Au enolate addition on
the intermediate complex F that would entail a disfavored
sp-to-sp2 carbon rehybridization via the strained transition
state G. Finally, a likely rate-determining,[30,31] protodeaura-
tion of D generates g-lactam (+)-2 f as the major enantio-
mer, the absolute configuration of which is in accord with
that deduced from circular-dichroism-based experiments.
In conclusion, we have developed a new gold-catalyzed
cycloisomerizative hydroalkylation affording regioselectively
4-vinyl-g-lactams. This transformation is stereospecific and
takes place with a total axis-to-center chirality transfer. The
required enantioenriched N-allenyl amide was successfully
obtained by means of an original Pd-catalyzed DYKAT pro-
cess.
Keywords: allene
transformation · gold · lactams · palladium
·
dynamic
kinetic
asymmetric
[1] a) C. Nieto-Oberhuber, M. P. MuÇoz, E. BuÇuel, C. Nevado, D. J.
Cꢃrdenas, A. M. Echavarren, Angew. Chem. 2004, 116, 2456–2460;
Angew. Chem. Int. Ed. 2004, 43, 2402–2406; b) A. Hoffmann-
Rçder, N. Krause, Org. Biomol. Chem. 2005, 3, 387–391; c) A. S. K.
Hashmi, Chem. Rev. 2007, 107, 3180–3211; d) H. C. Shen, Tetrahe-
dron 2008, 64, 3885–3903; e) E. Jimeꢄnez-Nuꢄn~ez, A. M. Echavar-
ren, Chem. Rev. 2008, 108, 3326–3350; f) D. J. Gorin, B. D. Sherry,
F. D. Toste, Chem. Rev. 2008, 108, 3351–3378; g) Z. Li, C. Brouwer,
C. He, Chem. Rev. 2008, 108, 3239–3265; h) A. Arcadi, Chem. Rev.
2008, 108, 3266–3325; i) N. Krause, C. Winter, Chem. Rev. 2011, 111,
1994–2009.
[2] a) J. J. Kennedy-Smith, S. T. Staben, F. D. Toste, J. Am. Chem. Soc.
2004, 126, 4526–4527; b) X. Yao, C. Li, J. Am. Chem. Soc. 2004,
126, 6884–6885; c) S. T. Staben, J. J. Kennedy-Smith, F. D. Toste,
Angew. Chem. 2004, 116, 5464–5466; Angew. Chem. Int. Ed. 2004,
43, 5350–5352; d) R. Nguyen, X. Yao, D. S. Bohle, C. Li, Org. Lett.
2005, 7, 673–675; e) A. Ochida, H. Ito, M. Sawamura, J. Am. Chem.
Soc. 2006, 128, 16486–16487; f) J.-H. Pan, M. Yang, Q. Gao, N.-Y.
Zhu, D. Yang, Synthesis 2007, 2539–2544; g) C.-Y. Zhou, C.-M. Che,
J. Am. Chem. Soc. 2007, 129, 5828–5829; h) H. Ito, Y. Makida, A.
Ochida, H. Ohmiya, M. Sawamura, Org. Lett. 2008, 10, 5051–5054.
[3] a) X. Jiang, X. Ma, Z. Zheng, S. Ma, Chem. Eur. J. 2008, 14, 8572–
8578; b) S. T. Staben, J. J. Kennedy-Smith, D. Huang, B. K. Corkey,
R. L. La Londe, F. D. Toste, Angew. Chem. 2006, 118, 6137; Angew.
Chem. Int. Ed. 2006, 45, 5991–5994.
Experimental Section
General procedure for gold-catalyzed hydroalkylation reaction: In
a
Schlenk tube, tetrabutylammonium hydroxide (1.25 mL, 1 mmol,
[4] a) G. Giambastiani, B. Pacini, M. Porcelloni, G. Poli, J. Org. Chem.
1998, 63, 804–807; b) G. Poli, G. Giambastiani, B. Pacini, Tetrahe-
dron Lett. 2001, 42, 5179–5182; c) G. Poli, G. Giambastiani, J. Org.
Chem. 2002, 67, 9456–9459; d) P.-O. Norrby, M. M. Mader, M.
Vitale, G. Prestat, G. Poli, Organometallics 2003, 22, 1849–1855;
e) S. Lemaire, G. Giambastiani, G. Prestat, G. Poli, Eur. J. Org.
Chem. 2004, 2840–2847; f) D. Madec, G. Prestat, E. Martini, P.
Fristrup, G. Poli, P.-O. Norrby, Org. Lett. 2005, 7, 995–998; g) G.
Maitro, G. Prestat, D. Madec, G. Poli, Synlett 2006, 1055–1059;
h) M. Bui The Thuong, S. Sottocornola, G. Prestat, G. Broggini, D.
Madec, G. Poli, Synlett 2007, 1521–1525; i) C. Kammerer, G. Prestat,
D. Madec, G. Poli, Chem. Eur. J. 2009, 15, 4224–4227; j) X. Bantreil,
G. Prestat, D. Madec, P. Fristrup, G. Poli, Synlett 2009, 1441–1444;
k) N. Krause, V. Belting, C. Deutsch, J. Erdsack, H.-T. Fan, B.
Gockel, A. Hoffmann-Rçder, N. Morita, F. Volz, Pure Appl. Chem.
2008, 80, 1063–1069; l) M. Asikainen, N. Krause, Adv. Synth. Catal.
2009, 351, 2305–2309; m) C. Winter, N. Krause, Angew. Chem. 2009,
121, 6457–6460; Angew. Chem. Int. Ed. 2009, 48, 6339–6342; n) S.
Belot, K. A. Vogt, C. Besnard, N. Krause, A. Alexakis, Angew.
Chem. 2009, 121, 9085–9088; Angew. Chem. Int. Ed. 2009, 48, 8923–
8926; o) N. Krause, ꢅ. Aksin-Artok, V. Breker, C. Deutsch, B.
Gockel, M. Poonoth, Y. Sawama, Y. Sawama, T. Sun, C. Winter,
Pure Appl. Chem. 2010, 82, 1529–1536; p) ꢅ. Aksin-Artok, N.
Krause, Adv. Synth. Catal. 2011, 353, 385–391; q) S. R. K. Minkler,
B. H. Lipshutz, N. Krause, Angew. Chem. 2011, 123, 7966–7969;
Angew. Chem. Int. Ed. 2011, 50, 7820–7823.
2.0 equiv, 0.8m solution in MeOH) was added to a solution of appropriate
N-allenyl b-ketoamide (0.5 mmol, 1.0 equiv) in dry cyclohexane (5 mL),
under argon atmosphere. The initially colorless solution turned bright
yellow and the gold complex AuBr3 (11 mg, 25 mmol, 5 mol%) was intro-
duced. The resulting mixture was stirred at 808C. After completion of
the reaction, monitored by TLC, the mixture was filtered on a pad of
silica gel eluting with pure AcOEt and concentrated in vacuo. The crude
product was purified by flash chromatography on silica gel.
General procedure for palladium-catalyzed amination reaction: The
chiral ligand L* (7.5 mol%) was added to a solution of [Pd2ACTHUNTRGNE(UGN dba)3]·CHCl3
(13 mg, 12.5 mmol, 2.5 mol%) in dry THF (0.5 mL). The reaction mixture
was stirred at room temperature for 10 min. Allenyl acetate (0.5 mmol,
1.0 equiv) diluted in dry THF (1 mL) was added by means of a cannula.
In another flask sodium hydride (26 mg, 0.65 mmol, 1.3 equiv, 60% dis-
persion in mineral oil) was slowly added to a solution of N-benzyltrifluor-
oacetamide (122 mg, 0.6 mmol, 1.2 equiv) in dry THF (1 mL). The result-
ing mixture was stirred at room temperature for 10 min and added via
cannula in the first flask. The resulting orange mixture was stirred at
room temperature and the completion of the reaction was monitored by
TLC. The reaction was quenched with a saturated solution of NH4Cl and
the aqueous layer was extracted with diethyl ether. The combined organ-
ic layers were dried on MgSO4 and concentrated in vacuo. The crude ma-
terial was purified by flash chromatography.
[5] N-Allenyl b-ketoamides 1a–d and 1 f were obtained from the appro-
priate propargyl alcohols according to the following sequence: O-
THP protection, hydroxymethylation, SN2’ LiAlH4-mediated reduc-
tion, O-acylation, Pd-catalyzed allylic amination with N-benzyltri-
fluoroacetamide, N-trifluoroacetamide hydrolysis, N-acylation. Com-
pound 1e was obtained by a variant of the above route entailing me-
sylation of penta-2,3-dien-1-ol, substitution with benzylamine, and
final acylation. 1aa was obtained by allylation of 1a. See Supporting
Information for details.
Acknowledgements
CNRS and UPMC are acknowledged for financial support. The sponsor-
ship of COST Action D40 “Innovative Catalysis: New Processes and Se-
lectivities” is kindly acknowledged. The authors are indebted to Dr. Eti-
enne Derat (UPMC) for simulation of the CD spectra of 6 f and 2 f. We
thank Prof. Hꢀlꢂne Lebel for fruitful discussions. We also thank Dr. B.
Pugin (Solvias) for the generous gift of a ligand kit for the initial screen-
ing.
[6] PtCl2, Ag
ACHTUNGNERTU(NNG OTf), CuACHNUTTRGEGNN(NU OTf)2, FeCl3, or [RhClCAHTNUGTERN(NUGN PPh3)3] proved totally
ineffective.
[7] The trans configuration between the newly formed stereocenters of
2b was, by analogy, extended to the other disubstituted lactams 2a–f
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3843

G. Poli, G. Prestat et al.
obtained in this study. Close similarities among the NMR spectra of
2a–f further strengthened our confidence in the configuration as-
signments.
[21] Enantiomeric ratios were determined by chiral HPLC SFC (5 f:
AD-H, CO2/iPrOH 90:10, 2.5 mLminꢁ1, 85 bar 2 f: OD-H, CO2/
iPrOH 85:15, 5.0 mLminꢁ1, 85 bar).
[8] The E configuration of the double bond in 2e and 2 f was unambigu-
ously determined [1H NMR (Jvic =15.0 Hz)] for both compounds.
[9] a) B. M. Trost, D. R. Fandrick, D. C. Dinh, J. Am. Chem. Soc. 2005,
127, 14186–14187; b) Y. Imada, M. Nishida, K. Kutsuwa, S. Muraha-
shi, T. Naota, Org. Lett. 2005, 7, 5837–5839; see also: c) A. Horvꢃth,
J.-E. Bꢆckvall, Chem. Commun. 2004, 964–965.
[10] B. M. Trost, D. L. Van Vranken, C. Bingel, J. Am. Chem. Soc. 1992,
114, 9327.
[11] See Supporting Information for details.
[12] T. P. Dang, H. B. Kagan, J. Chem. Soc. D 1971, 481.
[13] M. D. Fryzuk, B. Bosnich, J. Am. Chem. Soc. 1977, 99, 6262–6267.
[14] P. Von Matt, A. Pfaltz, Angew. Chem. 1993, 105, 614–615; Angew.
Chem. Int. Ed. Engl. 1993, 32, 566–569.
[15] Y. Wang, T. Sturm, M. Steurer, V. B. Arion, K. Mereiter, F. Spindler,
W. Weissensteiner, Organometallics 2008, 27 , 1119–1127.
[16] H.-U. Blaser, W. Brieden, B. Pugin, F. Spindler, M. Studer, A. Togni,
Top. Catal. 2002, 19, 3–16.
[17] a) S. Duprat de Paule, N. Champion, V. Ratovelomanana-Vidal, J.-P.
Genet, P. Dellis, French patent 0112499; PCT FR02/03146,
W003029259; b) S. Duprat de Paule, S. Jeulin, V. Ratovelomanana-
Vidal, J.-P. Genet, N. Champion, P. Dellis, Tetrahedron Lett. 2003,
44, 823–826.
[22] B. M. Trost, R. C. Bunt, R. C. Lemoine, T. L. Calkins, J. Am. Chem.
Soc. 2000, 122, 5968–5976.
[23] G. Poli, G. Prestat, F. Liron, C. Kammerer-Pentier, Top. Organomet.
Chem. 2012, 38, 1–64.
[24] a) T. Yamamoto, M. Akimoto, O. Saito, A. Yamamoto, Organome-
tallics 1986, 5, 1559–1567; b) C. Amatore, A. Jutand, G. Meyer, L.
Mottier, Chem. Eur. J. 1999, 5, 466–473.
[25] Intermediates A incorporate two stereogenic units: the axis, related
to the 1,3-disubstituted allene, and the plane, related to the unsym-
metrically substituted h3-allyl palladium moiety. As to the latter ste-
reogenic unit, the stereochemical descriptors of planar chirality of
substituted cyclophane type were adopted, considering Pd as the
pilot atom. Hence, the clockwise path Csp-CH-CH2 defines the Rp
descriptor whereas the anticlockwise path defines the Sp descriptor.
[26] Value obtained from the experimentally observed enantiomeric
ratio (86:14), according to the Boltzmann distribution at 300 K.
[27] Simulation of the CD spectra were performed by Dr. Etienne Derat
(Institut Parisien de Chimie Molꢀculaire, UPMC).
[28] N. Berova, L. Di Bari, G. Pescitelli, Chem. Soc. Rev. 2007, 36, 914–
931.
[29] Z. Zhang, C. Liu, R. E. Kinder, X. Han, H. Qian, R. A. Widenhoe-
fer, J. Am. Chem. Soc. 2006, 128, 9066–9073.
[18] R. Schmid, J. Foricher, M. Cereghetti, P. Schçnholzer, Helv. Chim.
Acta 1991, 74, 370–389.
[19] R. Schmid, E. A. Broger, M. Cereghetti, Y. Crameri, J. Foricher, M.
Lalonde, R. K. Mꢇller, M. Scalone, G. Schoettel, U. Zutter, Pure
Appl. Chem. 1996, 68, 131–138.
[30] Recent reports indicated that the kinetics of the protodeauration re-
action can be unexpectedly sluggish (see next reference). Further-
more, the presence of a base in the reaction conditions employed is
expected to further reduce the rate of this reaction.
[31] K. E. Roth, S. A. Blum, Organometallics 2010, 29, 1712–1716.
[20] These experiments were performed using the allenyl p-methoxyben-
zoate substrate, instead of the acetate (ꢀ)-3, and (R)-BINAP as the
ligand.
Received: December 12, 2011
Published online: February 29, 2012
3844
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Chem. Eur. J. 2012, 18, 3840 – 3844