Rhodium-Catalyzed Asymmetric Allylation of Malononitriles as Masked Acyl Cyanide with Allenes: Efficient Access to β,γ-Unsaturated Carbonyls

Article abstract of DOI:10.1002/chem.201804150

A rhodium-catalyzed regio- and enantioselective intermolecular allylation of malononitriles as masked acyl cyanides (MAC) with terminal and symmetrical internal allenes is reported. A Rh^I/Josiphos catalytic system combined with subsequent oxidative degradation of the primary adducts enables a straightforward access to α-branched, β,γ-unsaturated carbonyl compounds. The present protocol exhibits perfect atom economy in the allylation step and is characterized by a great functional group compatibility. Furthermore, the use of α-substituted malononitriles allowed for the construction of all-carbon quaternary centers.

Full text of DOI:10.1002/chem.201804150

A Journal of
Accepted Article
Title: Rhodium-catalyzed Asymmetric Allylation of Malononitriles as
Masked Acyl Cyanide with Allenes: Efficient Access to β,ɣ-
unsaturated Carbonyls
Authors: Bernhard Breit and Christian Grugel
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To be cited as: Chem. Eur. J. 10.1002/chem.201804150
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10.1002/chem.201804150
Chemistry - A European Journal
COMMUNICATION
Rhodium-catalyzed Asymmetric Allylation of Malononitriles as
Masked Acyl Cyanide with Allenes: Efficient Access to β,ɣ-
unsaturated Carbonyls
Christian P. Grugel, and Bernhard Breit*[a]
Abstract:
A
rhodium-catalyzed regio- and enantioselective
suitable nucleophiles: While Trost reported the use of 1-
phenylsulfonyl-1-nitorethane in Pd-catalysis,[5a] P. A. Evans
utilized silylated cyanohydrines in Rh-catalyzed allylations to
intermolecular allylation of malononitriles as masked acyl cyanides
(MAC) with terminal and symmetrical internal allenes is reported. A
Rh(I)/Josiphos catalytic system combined with subsequent oxidative
degradation of the primary adducts enables a straightforward access
to α-branched, β,ɣ-unsaturated carbonyl compounds. The present
protocol exhibits perfect atom economy in the allylation step and is
characterized by a great functional group compatibility. Furthermore,
the use of α-substituted malononitriles allows for the construction of
all-carbon quaternary centers in an asymmetric fashion.
access
β,ɣ-unsaturated
ketones.[5b,c]
To
access
the
corresponding carboxylic acid ester adducts, acetoxymalonates
have been used by Trost and Helmchen in Pd-catalyzed allylic
substitution protocols.[6] Most recently, Stoltz and co-workers
utilized an α-oxygenated malononitrile derivative in iridium-
catalyzed allylic substitutions — a masked acyl cyanide reagent
first developed by Yamamoto and Nemoto, in which the transient
acyl cyanide could be transformed into a multitude of carboxylic
acid derivatives after becoming “unmasked”.[7,8] In a similar
strategy, Helmchen made use of the unsubstituted malononitile
itself as MAC reagent by developing a selective strategy to
oxidize the primary allylic adduct resulting in the same acyl
cyanide intermediate, which allows for being trapped with
methanol to form the corresponding methyl ester.[9]
Since the seminal reports of Corey and Seebach about
reversing the inherent electrophilicity of carbonyl groups – later
referred to as “umpolung” reactions – numerous concepts
unravelling the nucleophilic properties of the acyl group have
emerged and successfully applied in the syntheses of complex
molecules.[1,2] Despite the widespread use of cyanohydrines,
thioacetals and cyanides as d1-synthons, this concept has so far
only been scarcely applied in transition metal-catalyzed
reactions.[3] However, given the utility of branched, chiral, α-
vinylated carbonyl compounds as well as the difficulty of
accessing them by conventional methods, promoting research in
this field is of tremendous interest. In this respect, various
groups implemented the use of formyl and acyl anion
equivalents as well as masked acyl cyanides (MAC) in allylic
substitution reactions, by which existing methods in terms of
efficient carbon-carbon bond formation were successfully
complemented.
Previous work: Regular polarity nucleophiles
O
O
R‘
OH
- CO2
RhI, ligand
Me
or
O
R
*
R
R
R‘
γ,δ-unsaturated
carbonyls
R‘
·
O
O
R‘
R’
O
O
O
H
R
This work: “Inverse” polarity nucleophile
RO
R’
R’
R’
O
1) RhI, ligand
2) [O]
R‘
R’’
*
·
+
RO
NC
CN
R’
R’’
R2O2C
CO2R2
NO2
SO2Ph
Trost5a
CN
NC
CN
N
H
NC
CN
β,γ-unsaturated
carbonyls
N
R
R
OTBS
OR
Stoltz7
OCOR
Trost, Helmchen6
H
Carreira4
P. A. Evans5b,c
Helmchen9
Scheme 2. Strategy for the rhodium-catalyzed asymmetric construction of α-
vinylated carbonyl compounds.
Scheme 1. Strategies for the rhodium-catalyzed asymmetric construction of α-
vinylated carbonyl compounds.
Despite their respective synthetic utliity and their excellent
regio- and stereoelectivities, all these methods represent allylic
substitution reactions and thus violate the principle of atom
economy[10] by releasing stoichiometric amounts of waste in the
course of the reaction. Moreover, the respective allylic
electrophiles as well as the umpoled reagents often require
multi-step syntheses, thereby diminishing their attractiveness
regarding sustainability. Throughout the last years, we reported
In 2015 Carreira and co-workers introduced N,N-
dialkylhydrazones as neutral formyl anion equivalent in iridium-
catalyzed asymmetric allylic substitutions of allylic carbonates.[4]
Additionally, acyl anion equivalents were also reported to be
[a]
M.Sc. Christian P. Grugel, and Prof. Dr. Bernhard Breit
Albert-Ludwigs-Universität Freiburg
on
a
series of rhodium-catalyzed chemo-, regio- and
Institut für Organische Chemie
Albertstr. 21, 79104 Freiburg (Germany)
E-mail: bernhard.breit@chemie.uni-freiburg.de
enantioselective coupling reactions involving allenes[11,12] and
alkynes[13,14] as allylic electrophile precursors with various
pronucleophiles, thus establishing
alternative to the classic allylic alkylation. So far, regular polarity
a more atom-economic
Supporting information for this article is given via a link at the end of
the document.
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10.1002/chem.201804150
Chemistry - A European Journal
COMMUNICATION
nucleophiles have been used as coupling partners exclusively.
To overcome this restraint, we envisioned that making use of the
inherent nucleophilicity of malononitrile combined with its easily
convertible nature as expounded by Helmchen comprises a
soared to 89.5:10.5 in favor of the (R)-product (entry 3). With
J003-1, a Josiphos ligand bearing two dicyclohexylphosphine
rests, 3a was obtained almost quantitatively but in a lower
enantiomeric ratio (entry 4). Unfortunately, the results obtained
with more electron-rich or electron-deficient ligands (entries 5
and 6) were inferior. The same holds for exchanging one of the
dicyclohexylphosphine rests with di-tert-butylphosphine (entry 7)
in J009-1 as well as when using J011-1 (entry 8), which lead to
the ultimate decision that J003-1 might be the ligand of choice
since it showed the highest overall reactivity. Generally, it is
known that the acidic co-catalyst similarly affects the outcome of
the reaction[17] and by exchanging 4-trifluoromethyl benzoic acid
with pyridinium p-toluenesulfonate (PPTS) while simultaneously
lowering the reaction temperature to 60 °C, 3a was formed
already in a good enantiomeric ratio of 90.5:9.5 (entry 9).
Further improvement could be achieved by performing the
reaction in acetonitrile instead of 1,2-dichloroethane (entry 10).
Interestingly, simply by inverting the relative molar ratio of 1 and
2a, the yield of adduct 3a as well as its enantioselectivity could
ultimately be increased to 99% and 92.5:7.5 er respectively
(entry 11). However, for different allenes the conditions in entry
10 proved to be superior.
convenient “inverse” polarity reagent to enable
a more
sustainable access to β,ɣ-unsaturated carbonyl compounds.
We initiated our investigations by drafting 6-phenylhexa-1,2-
diene (2a) as model electrophile. In an initial attempt with 2.5
mol% [Rh(cod)Cl]2 and 7.5 mol% DPEphos in the presence of
50 mol% 4-trifluoromethyl benzoic acid as co-catalyst,
malononitrile was already found to be fairly reactive and the
desired adduct 3a was formed in 81% yield (table 1, entry 1).
Table 1. Optimization of Reaction Conditions.[a]
[Rh(cod)Cl]2 (2.5 mol%)
ligand (7.5 mol%)
4-CF3C6H4COOH (50 mol%)
NC
CN
NC
CN
+
•
DCE (0.25 M)
80 °C, 16 h
1
2a
3a
Entry
Ligand
R
R’
Yield
/ %
e.r.
1
2
3
4
5
6
DPEphos
J001-1
J002-1
J003-1
J006-1
J007-1
--
--
Ph
t-Bu
Cy
Cy
Cy
81
91
62
99
17
80
rac
60:40
Table 2. Evaluation of the reaction scope.[a]
Ph
Ph
Cy
[Rh(cod)Cl]2 (2.5 mol%)
89.5:10.5
72:28
Josiphos J003-1 (7.5 mol%)
PCy2
PCy2
NC
R
CN
R
PPTS (50 mol%)
NC
CN
+
Fe
R
R
•
MeCN (0.25
M)
60 °C, 16-18h
1
2
3
J003-1
1.0 eq.
2.0 eq.
3,5-CF3C6H3
60:40
NC
CN
NC
CN
NC
CN
NC
CN
3,5-Me-4-
MeOC6H2
63.5:36.5
Ph
Ph
C14H29
n
3ab
99 %
92.5:7.5 er
n = 1 3d 80 %, 85:15 er
n = 2 3e 81 %, 90.5:10.5 er
n = 3 3f 48 %, 88.5:11.5 er
3b
84 %
91:9 er
3c
87 %
92.5:7.5 er
7
J009-1
J011-1
J003-1
J003-1
J003-1
Cy
4-CF3C6H4
Cy
t-Bu
t-Bu
Cy
48
27
82
70
99
87:13
81.5:18.5
90.5:9.5
91:9
8
NC
CN
NC
CN
NC
CN
NC
CN
9[b]
10[c]
11[d]
BnO
PMBO
THPO
BOMO
3i
99 %
90.5:9.5 er
1:1 dr
3g
99 %
90:10 er
3h
86 %
89:11 er
3j
66 %
90:10 er
Cy
Cy
Cy
Cy
92.5:7.5
NC
CN
NC
CN
NC
CN
NC
CN
OBz
OTBS
PhO
Cl
[a] Reaction Conditions: 1 (0.2 mmol), 2a (0.4 mmol), [Rh(codCl)]2 (2.5 mol%),
ligand (7.5 mol%), acid co-catalyst (50 mol%), DCE (1.0 ml), 80 °C, 16 h. [b]
Reaction performed at 60 °C with 50 mol% PPTS as additive. [c] Reaction run
in MeCN (0.25 M). [d] Reaction performed with an inverted molar ratio of 1:2a
= 2:1.
3k
93 %
93:7 er
3l
91%
91.5:8.5 er
3m
85 %
92.5:7.5 er
3n
75 %
90.5:9.5 er
NC
CN
NC
CN
NC
CN
NC
CN
MeO2C
NC
PhS
Br
n
Me
n = 1 3o 34 %, 87:13 er
n = 2 3p 48 %, 87:13 er
n = 3 3q 75 %, 87:13 er
3r
89 %
92.5:7.5 er
3s
93 %
90.5:9.5 er
3t
84 %
90:10 er
PR’2
PR2
Josiphos
J00x-1
DPEphos
O
Fe
PPh2
PPh2
NC
CN
NC
CN
NC
CN
=
Ph
In order to investigate the potential for the development of an
asymmetric modification thereof, several privileged ligands were
tested with the Josiphos ligand class providing the most
promising results.[15] By employing Josiphos J001-1, 3a was
isolated in 91% yield even though its enantioselectivity required
further optimization (entry 2). Gratifyingly, the Josiphos ligand
backbone allows for great variety in terms of substitution
pattern[16] and simply by exchanging one diphenylphosphine
substituent with the more electron-rich di-tert-butylphosphine
moiety in J002-1, the reactions’ enantioselectivity considerably
PhSO2
PhthN
Ph
3w
3u
80 %
90.5:9.5 er
3v
81 %
93:7 er
X-Ray
44 %
95:5 er
Z:E = 3:1
[a] All yields given as isolated yields. Enantioselectivities determined by HPLC
or GC on chiral stationary phases. Absolute configuration assigned by
analogy[18]; [b] Reaction performed with an inverted molar ratio of 1:2a = 2:1.
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COMMUNICATION
With these optimized conditions in hand, we next explored the
substrate scope and functional group compatibility of the
developed protocol (Table 2).
(Table 3).[9] The corresponding β,ɣ-unsaturated methyl esters
were obtained in good to excellent yields after two steps without
any loss of enantioselectivity observable. Aside from utilizing
malononitrile as formyl surrogate, substituted malononitriles
allow for the efficient generation of all-carbon quaternary centers
(Table 4). In this respect, α-aliphatic (5a), allylated (5b) as well
as α-aromatic malononitriles (5c) reacted smoothly with allene
2a at 50 °C and the corresponding adducts 6a-c were obtained
in excellent yields and only marginally lower enantiomeric ratios.
Hence, the present protocol provides facile access to
enantiomerically enriched α-quaternary malononitriles which can
serve as starting point for various further transformations.[22]
Efficient[19] and enantioselective coupling reactions occur
with a variety of different substitution patterns starting from
allenes easily synthesized in one or two steps from commercially
available starting materials.[20] In this respect, various aliphatic
allenes reacted smoothly to the corresponding adducts 3a-c in
up to quantitative yield and good enantiomeric ratios of up to
92.5:7.5. Additionally, also branched cycloaliphatic allenes
proved to be suitable reaction partners (3d-f), even though their
reactions proceed with slightly lower enantioselectivities. In case
of cycloheptylallene however, a significantly lower yield was
observed – presumably owing to its increased steric bulk. Next,
we examined the suitability of higher functionalized allenes as
reaction partners. In this respect, a variety of protected alcohols
(3g-m) were well tolerated and the corresponding adducts were
obtained in excellent yields and good enantiomeric ratios.
Superior results were obtained for allenes bearing longer
methylene spacers (3k-m) between the heteroatom and the
allene with up to 93 % yield of the malononitrile adducts and
93:7 er. Halogenated allenes (3n-q) were also suitable reaction
partners – even though they showed slightly lower reactivities.
Also the length of the methylene spacer proved to be a crucial
feature in case of the bromoallenes (3p-r) as the farther away
the bromine substituent was in relative distance to the reacting
allene part, the better were the yields of their malononitrile
adducts. Contrarily, higher functionalized allenes bearing a
methyl ester (3r), a nitrile (3s), a thioether (3t), a sulfone (3u)
Table 4. Allylation of α-substituted malononitriles: Formation of all-carbon
quaternary centers.[a]
[Rh(cod)Cl]2 (2.5 mol%)
Josiphos J003-1 (7.5 mol%)
PPTS (50 mol%)
CN
CN
PCy2
PCy2
R‘
NC
CN
+
Fe
R
•
MeCN (0.25
50 °C, 16-18h
M)
R
R’
J003-1
5
2
6
CN
CN
CN
CN
CN
CN
Ph
Ph
=
Ph
Ph
Ph
X-Ray
6a
6b
6c
99 %
85.5:14.5 er
91 %
85.5:14.5 er
99 %
88:12 er
[a] Reaction Conditions: 1) 5 (0.2 mmol), 2 (0.4 mmol), [Rh(codCl)]2 (2.5
mol%), Josiphos J003-1 (7.5 mol%), PPTS (50 mol%), MeCN (0.8 ml), 50 °C,
16 h.
and
a
phthalimide (3v) were well tolerated and the
corresponding adducts obtained in excellent yields and high
enantioselectivities. Notably, even a sterically more challenging
symmetric internal allene proved to be a decent reaction partner
as adduct 3w was obtained in a Z/E ratio of 3:1 and excellent
95:5 er suggesting the prevalence of a kinetic resolution.[21]
In order to highlight the overall synthetic practicability of the
present method, a gram-scale reaction was carried out and
1.26 g of 3b were obtained with an enantiomeric ratio of 91:9
mirroring the results from the initial small-scale catalysis
(Scheme 3).
O
7
a)
Table 3. Oxidative cleavage of the malononitrile scaffold: Synthesis of β,ɣ-
CN
99%
1:1 dr
91:9 er
H2N
Ph
unsaturated methyl esters.
1) [Rh(cod)Cl]2, J003-1, PPTS
MeCN, 60 °C, 16 h
NC
CN
MeO
R
O
2.5 mol% [Rh(cod)Cl]2
7.5 mol% Josiphos J003-1
50 mol% PPTS
N
HN
NC
CN
1
NC
CN
+
R
8
quant.
93.5:6.5 er
•
NH2
b)
c)
H2N
Ph
+
2) Li2CO3, MMPP, MeOH
0 °C, 3h
Ph
MeCN, 60 °C, 16 h
1
2
4
Ph
·
3b
75 %
91:9 er
8.0 mmol scale
2b
HO
OH
N
N
9
95%
93.5:6.5 er
MeO
O
MeO
O
MeO
O
H2N
NH2
Ph
MeO2C
PhthN
Ph
Scheme 3. Gram-scale synthesis of malononitrile adduct 3b and assorted
transformations thereof. Reaction Conditions: a) PdCl2 (10 mol%), acetamide
(4.2 eq.),THF/H2O = 3:1, r.t., 48 h; b) N2H4·H2O (2.0 eq.), EtOH, 90 °C, 16 h;
c) NH2OH (50 % aq., 2.2 eq.), EtOH, 90 °C, 16 h, 95 %.
4a
89 %
92.5:7.5 er
4r
80 %
4v
73 %
92.5:7.5 er[b]
93:7 er[b]
[a] Reaction Conditions: 1) 1 (0.2 mmol), 2 (0.4 mmol), [Rh(codCl)]2 (2.5
mol%), Josiphos J003-1 (7.5 mol%), PPTS (50 mol%), MeCN (0.8 ml), 60 °C,
16 h. 2) Li2CO3 (1.5 eq.), MMPP (0.75 eq.), MeOH (1.3 ml), 0 °C, 3h. [b]
Enantiomeric ratio of the corresponding malononitrile adducts 3r and 3v.
Besides its potential as transient acyl cyanide precursor, the
malononitrile scaffold also allows for
a variety of other
transformations. Treating adduct 3b with acetamide and catalytic
amounts of PdCl2 selectively enables a monohydration and
gives rise to α-cyanoacetamides (7) in quantitative yields. A
condensation with hydrazine leads to 1,4-diaminopyrazoles (8),
which represent interesting scaffolds in medicinal chemistry.[23a]
The same holds for malonohydroxamamides (9),[23b,c] which can
be easily obtained by refluxing adduct 3b with an excess of
hydroxylamine in ethanol.
To demonstrate the utility of this newly developed protocol,
the adducts 3 were subjected to an oxidative cleavage of the
malononitrile scaffold following the above mentioned procedure
first reported by Helmchen et al. assisted by magnesium
monoperoxyphthalate (MMPP) under gently basic condtions
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10.1002/chem.201804150
Chemistry - A European Journal
COMMUNICATION
5072-5074; e) M. Seemann, M. Schöller, S. Kudis, G. Helmchen, Eur.
J. Org. Chem. 2003, 2122-2127.
To conclude, we have accomplished the selective allylation of
malononitrile as masked acyl cyanide starting from terminal and
internal allenes as atom economic π-allyl precursors. The
present method enables the construction of tertiary and
quaternary all- carbon stereocenters under mild conditions in
good to excellent yields, perfect regioselectivities and good to
high enantiose- lectivities. By combining this strategy with
Helmchen’s method for the oxidative degradation of the
malononitrile scaffold, β,ɣ-unsaturated carbonyl compounds
were easily accessed. Furthermore, underscoring the utility of
the obtained adducts, one-step transformations to 3,5-
diaminopyrazoles and malonohydroxamamides, systems of
biological and medicinal interest, were conducted.
[7]
[8]
J. C. Hethcox, S. E. Shockley, B. M. Stoltz, Org. Lett. 2017, 19, 1527–
1529.
a) H. Nemoto, Y. Kubota, Y. Yamamoto, J. Org. Chem. 1990, 55,
4515−4516; b) H. Nemoto, X. Li, R. Ma, I. Suzuki, M. Shibuya,
Tetrahedron Lett. 2003, 44, 73−75; c) H. Nemoto, T. Kawamura, N.
Miyoshi, J. Am. Chem. Soc. 2005, 127, 14546−14547; d) H. Nemoto, R.
Ma, T. Kawamura, M. Kamiya, M. Shibuya, J. Org. Chem. 2006, 71,
6038−6043; e) H. Nemoto, T. Kawamura, K. Kitasaki, K. Yatsuzuka, M.
Kamiya, Y. Yoshioka, Synthesis 2009, 1694− 1702.
[9]
S. Förster, O. Tverskoy, G. Helmchen, Synlett 2008, 18, 2803–2806.
[10] B. M. Trost, Science 1991, 254, 1471–1477.
[11] For a recent review, see: P. Koschker, B. Breit, Acc. Chem. Res. 2016,
49, 1524-1536.
[12] For examples of C−C bond formation, see: a) C. Li, B. Breit, J. Am.
Chem. Soc. 2014, 136, 862-865; b) T. M. Beck, B. Breit, Angew. Chem.
2017, 129, 1929-1933; Angew. Chem., Int. Ed. 2017, 56, 1903-1907; c)
C. P. Grugel, B. Breit, Org. Lett. 2018, 20, 1066–1069; d) P. P. Bora,
G.-J. Sun, W.-F. Zheng, Q. Kang, Chin. J. Chem. 2018, 36, 20–24.
[13] For a recent review, see: A. Haydl, B. Breit, T. Liang, M. J. Krische,
Angew. Chem. 2017, 129, 11466-11480; Angew. Chem., Int. Ed. 2017,
56, 11312-11325.
Conflict of interest
The authors declare no conflict of interest.
[14] For examples of C−C bond formation, see: a) T. M. Beck, B. Breit, Org.
Lett. 2016, 18, 124-127; b) F. A. Cruz, Z. Chen, S. I. Kurtoic, V. M.
Dong, Chem. Commun. 2016, 52, 5836-5839; c) C. Li, C. P. Grugel, B.
Breit, Chem. Commun. 2016, 52, 5840-5843; d) T. M. Beck, B. Breit,
Eur. J. Org. Chem. 2016, 5839-5844; e) F. A. Cruz, V. M. Dong, J. Am.
Chem. Soc. 2017, 139, 1029-1032; f) F. A. Cruz, Y. Zhu, Q. D.
Tercenio, Z. Shen, V. M. Dong, J. Am. Chem. Soc. 2017, 139, 10641-
10644..
Acknowledgements
This work was supported by the DFG and the Fonds der
Chemischen Industrie. We thank Umicore, BASF, and Wacker
for generous gifts of chemicals. C.P.G. is grateful for a Ph.D.
fellowship from the Fonds der Chemischen Industrie. Dr. Daniel
Kratzert (University of Freiburg) is acknowledged for providing
highly qualified X-Ray analyses. Technical support by Gamze
Ciplak and Joshua Emmerich (both University of Freiburg) for
laboratory assistance and HPLC separations is acknowledged.
[15] For details, see Supporting Information.
[16] For an exemplified ligand synthesis procedure, refer to the Supporting
Information.
[17] For details concerning the effect of different additives and solvent
systems, see Supporting Information.
Keywords: malononitrile • MAC reagent • asymmetric catalysis
[18] The absolute configuration was assigned as (R) by comparison with the
optical rotation of known compound 3b. For details, see the Supporting
Information.
• allylation • quaternary carbon centers
[19] A formation of diallylmalononitriles stemming from an over-reaction of
the formed products 3 was not observed in any case.
[1]
a) E. J. Corey, D. Seebach, Angew. Chem. Int. Ed. 1965, 4, 1075-1077;
b) D. Seebach, Angew. Chem. 1969, 81, 690-700; Angew. Chem. Int.
Ed. 1969, 8, 639-649; c) D. Seebach, Angew. Chem 1979, 91, 259-278;
Angew. Chem. Int. Ed. 1979, 18, 239-258.
[20] For details on substrate synthesis, see the Supporting Information.
[21] For an example of
a kinetic resolution, see: A. B. Pritzius, B.
Breit, Angew. Chem. 2015, 127, 16044–16048; Angew. Chem. Int.
Ed. 2015, 54, 15818–15822.
[2]
[3]
a) Umpoled Synthons (Ed.: T. A. Hase), Wiley: New York, 1987; b) A. B.
Smith, C. M. Adams, Acc. Chem. Res. 2004, 37, 365-377; c) A. T. Biju,
N. Kuhl, F. Glorius, Acc. Chem. Res. 2011, 44, 1182-1195.
[22] For selected examples on transformations of the malononitrile scaffold,
see: a) R. Fuks, Tetrahedron 1973, 29, 2147–2151; b) V. G. Granik, A.
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10.1002/chem.201804150
Chemistry - A European Journal
COMMUNICATION
Entry for the Table of Contents
COMMUNICATION
1) RhI / Josiphos J003-1
Christian P. Grugel, Bernhard Breit*
PPTS
PCy2
PCy2
O
MeCN, 60 °C, 16 h
Fe
NC
CN
+
R‘
R’’
*
·
MeO
Page No. – Page No.
2) oxidative methanolysis
R’
R’’
J003-1
Rhodium-catalyzed
Asymmetric
• enantioselective C-C bond formation
• “inverse” polarity nucleophile
• with terminal and internal allenes
23 examples
up to 99% yield
up to 95:5 er
Allylation
of
Malononitriles as
Masked Acyl Cyanide with Allenes:
Efficient Access to β,ɣ-unsaturated
Carbonyls
Reactivity overturned:
A
rhodium-catalyzed regio- and enantioselective
intermolecular allylation of malononitrile as masked acyl cyanide (MAC) with
allenes is reported. A Rh(I)/Josiphos catalytic system combined with a subsequent
oxidative degradation of the primary adducts enables a straightforward access to α-
branched, β,ɣ-unsaturated carbonyl compounds – products of formal methyl
formiate addition.
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