Enantioselective Synthesis of trans-Vicinal Diamines via Rhodium-Catalyzed [2+2] Cycloaddition of Allenamides

Article abstract of DOI:10.1002/adsc.201800021

An efficient protocol for the enantioselective Rh-catalyzed intermolecular head-to-head [2+2] cycloaddition of allenamides was developed. A variety of enantio-enriched cyclobutane-1,2-diamine derivatives were achieved in good yields with good to excellent enantioselectivities. (Figure presented.).

Full text of DOI:10.1002/adsc.201800021

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DOI: 10.1002/adsc.201800021
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Enantioselective Synthesis of trans-Vicinal Diamines via
Rhodium-Catalyzed [2+2] Cycloaddition of Allenamides
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Wei-Feng Zheng,a Gui-Jun Sun,a Liang Chen,a and Qiang Kanga,*
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Key Laboratory of Coal to Ethylene Glycol and Its Related Technology, Fujian Institute of Research on the Structure of
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Matter, Chinese Academy of Sciences, 155 Yangqiao Road West, Fuzhou, 350002
E-mail: kangq@fjirsm.ac.cn
Received: January 5, 2018; Revised: March 11, 2018; Published online: &&&, &&&&
Supporting information for this article is available on the WWW under https://doi.org/10.1002/adsc.201800021
transition-metal catalyzed asymmetric protocols still
remained challenge, due to the native ability of
diamines as effective bidentate ligands to transition
Abstract: An efficient protocol for the enantiose-
lective Rh-catalyzed intermolecular head-to-head
[2+2] cycloaddition of allenamides was developed.
metal catalysts. Although these elegant methods have
A variety of enantio-enriched cyclobutane-1,2-dia-
been successfully achieved for access to chiral vicinal
mine derivatives were achieved in good yields with
diamines, the development of direct and efficient
good to excellent enantioselectivities.
enantioselective approach for synthesis of chiral 1,2-
diamines is still highly demanded.
Keywords: rhodium; diamine; allenamide; enantio-
selective
Recently we disclosed a rhodium-catalyzed inter-
molecular head-to-head [2+2] cycloaddition[11] of
allenamides[12] to generate vicinal diamines. This
method is useful for the direct preparation of a variety
30 Chiral vicinal diamines and their derivatives are of differentially protected cyclobutane-1,2-diamines
31 important components found in nature products, drugs with high regioselectivity.[13] Herein, we report an
32 with notable biological properties[1] and in ligands for enantioselective version of this transformation to
33 asymmetric metal catalysis and organocatalysis.[2] achieve enantio-enriched vicinal diamines along with
34 Therefore, the development of efficient strategies for the results of mechanistic experiments that shed light
35 the synthesis of chiral 1,2-diamines is of longstanding on the origin of the enantioselectivity in this asym-
36 interest in organic synthesis.[3,4] In recent years, several metric catalyst system.
37 possible strategies have been demonstrated, including
The development of an enantioselective [2+2]
38 inter-[5] or intra-[6] diamination of alkenes, diaza-Cope cycloaddition reaction began with the investigation of
39 rearrangement,[7] ring opening of aziridines,[8] reduc- the chiral ligands by using allenamide 1a as model
40 tive coupling of imines or N-sulfinylimines,[9] and substrate (Scheme 2). In the presence of 5 mol% of
41 nitro-Mannich reaction (Scheme 1).[10] Among them, [Rh(COD)Cl]2 in 1,2-dichlorobenzene (ODCB) at
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808C, no reaction was observed when employing
chiral ligands such as JosiPHOS, (R,R)-DACH-
Naphthyl Trost Ligand and spiro-diphosphine ligand
(L1–L3). Pleasingly, ligands with central chirality L4–
L6 exhibited catalytic activity for this asymmetric
transformation, albeit with poor yields (15–49%) and
moderate ee values (37–57%). Fortunately, diphos-
phine ligands with axial chirality is superior for the
title reaction: (S)-BINAP (L7) was found to be
optimal in terms of reactivity and enantioselectivity,
providing the desired [2+2] cycloaddition product 2a
in 60% yield with 80% ee. Inferior results were
obtained while L8 and L9 were employed, in which
bearing 4-methyl and 3,5-dimethyl substituents on the
phenyl ring, respectively. The examination of L10 and
L11 showed that lower enantioselectivities were
Scheme 1. Enantioselective approaches toward chiral vicinal
diamines.
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observed compared with (S)-BINAP (L7). Further conditions, affording the desired chiral vicinal diamine
screening of reaction temperature, concentration, 2r in 93% yield with 96% ee.
solvents, additives and loading of catalyst revealed
that the optimal reaction conditions for enantioselec-
tive Rh-catalyzed intermolecular head-to-head [2+2]
cycloaddition of allenamides as the following: 5 mol%
of [Rh(COD)Cl]2, 12 mol% (S)-BIANP in 1,2-dichlor-
obenzene (0.05 M) at 608C. Under the optimal
reaction conditions, chiral vicinal diamines 2a was
10 obtained in 73% yield with 92% ee (for details, see
11 Table S1–S5 in the Supporting Information).
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Scheme 3. Substrate scope of Ts-protected allenamides.
Furthermore, allenamides with different sulfonyl
protected groups were conducted to investigate the
generality of current protocol (Scheme 4). The cyclo-
addition of mesyl-derived N-benzylallenamide 1s
afforded the corresponding product 2s in 60% yield
with 92% ee. N-arylsulfonyl-substituted substrates 1t–
Scheme 2. Initial screening for asymmetric [2+2] cycloaddi-
tion reaction.
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Under the optimized reaction conditions, a variety
39 of tosyl-protected allenamides were investigated and
40 the results are summarized in Scheme 3. N-Benzyl
41 allenamides with different substituents on the phenyl
42 rings such as electron-rich para-methyl, methoxy or
43 dimethylamino and electron-deficient para-fluoro,
44 bromo or trifluoromethyl benzyl worked smoothly to
45 afford chiral 1,2-diamine derivatives 2a–2i in 61–95%
46 yields with 81–99% ee. Allenamides containing heter-
47 ocyclic moiety were well tolerated to furnish the
48 corresponding products (2j–2k) with good to excellent
49 enantioselectivities. N-phenylethyl and 3,3-diphenyl-
50 propyl allenamides (1l, 1m) also delivered the
51 expected products with 99% and 97% ee, respectively.
52 Introduction of aliphatic chain or ring group into
53 substrates (1n–1q) resulted in the desired [2+2]
54 dimerization products with a slight decrease in
55 enantioselectivities. Allenamide with silyl ether (1r)
56 was suitable substrate under the optimal reaction
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Scheme 4. Scope of allenamides with different sulfonyl
protected groups.
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1v consistently produced the desired cyclobutane-1,2-
diamines in 73–83% yields with 87–90% ee values.
Para-substitution of N-sulfonyl phenyl rings with
electron-donating (OMe) or electron-withdrawing
(NO2) groups had no significant influence on the
outcome of the title reaction. However, substrate 1w
with 2,4,6-trimethyl groups at the N-sulfonyl phenyl
ring, exhibited sluggish reactivity and poor enantiose-
lective control. Further increasing the steric hindrance
10 on N-sulfonyl phenyl ring (1x) completely suspended
11 conversion of title reaction, probably due to preven-
12 tion of coordination between Rh complex and sub-
13 strate with the sterically bulky group. The absolute
14 configuration of product 2u was confirmed by a
15 single-crystal X-ray analysis (Figure 1, for details, see
Figure 2. Hammett-plot of para-substituted N-benzyl allena-
mides.
16 the Supporting Information).[14]
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A proposed mechanism for the [2+2] cycloaddi-
tion of allenamides based on the Hammett-plot study
is depicted in Scheme 6. The reaction of allenamide 1
with Rh catalyst would regioselectively produce the
rhodium-acyclopentane (intermediate I), which would
undergo enantioselective controlled reductive elimina-
tion to afford optically active cyclobutane-1,2-diamine
2 as final product. The observed high regioselectivity
of the reaction is attributed the regioselective forma-
tion of metallacycle I, which might be controlled by
the electronic and steric effects of the substituent of
allenamide 1. On the basis of the results of our
previous mechanistic work[13] and the scope of differ-
Figure 1. X-ray derived ORTEP of 2u with thermal ellipsoids
shown at the 35% probability level (Symmetry transforma-
tions used to generate equivalent atoms: #1 Àx+1,Ày+1,z)
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To demonstrate the practicality of this protocol, a ent sulfonyl substituents allenamides (Scheme 4), the
33 gram-scale enantioselective [2+2] cycloaddition reac- sulfonyl group is crucial for the successful head-to-
34 tion of allenamide 1u (0.991 g/3 mmol) was conducted head [2+2] cycloaddition.
35 in the presence of 3 mol% of [Rh(COD)Cl]2 and
36 6 mol% of (R)-BINAP in ODCB at 408C. Gratify-
37 ingly, the reaction proceeded smoothly to afford 2u in
38 88% yield with 92% ee (Scheme 5).
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Scheme 5. Gram-scale reaction.
Scheme 6. Proposed mechanism.
To gain a better understanding of the mechanistic
51 details of this reaction, the Hammett-plot study was
In conclusion, we have developed an efficient
52 performed with various para-substituted N-benzyl rhodium catalyzed enantioselective head-to-head [2+
53 allenamides (1= +0.24, R2 =0.97, Figure 2), in which 2] cycloaddition of allenamides for synthesize various
54 electron-deficient substrates led to a higher initial optically active vicinal diamine derivatives. The enan-
55 rate. The Hammett-plot experiments indicate that the tio-enriched vicinal diamine derivatives were obtained
56 positive charge might be less likely formed in the in moderate to good yields with good to excellent
57 transition state of the catalytic cycle.
enantioselectivities. This method features high regio-
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and enantioselectivity, mild reaction conditions and
toleration of different functional groups. Mechanistic
studies show that metallacycle transition state might
be involved in catalytic cycle and the sulfonyl group is
crucial for this transformation.
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Experimental Section
General procedure for Rh-catalyzed enantioselective [2+2]
cycloaddition of allenamide. In a Schlenk tube, [Rh(COD)
Cl]2 (7.4 mg, 0.015 mmol), (S)-BINAP (22.4 mg, 0.036 mmol)
and allenamide 1 (0.3 mmol) were dissolved in anhydrous
1,2-dichlorobenzene (6 mL) under a nitrogen atmosphere
and stirred at 608C or 408C. After completion of the reaction
(monitored by TLC), the reaction mixture was quenched
with H2O and extracted with CH2Cl2 (10 mL3 3). The
organic layer was washed with brine, dried over Na2SO4,
filtrated, concentrated and purified by silica gel column
chromatography to afford the corresponding product 2.
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Acknowledgements
This work was supported by the Strategic Priority Research
Program of the Chinese Academy of Sciences, Grant
No. XDB20000000 and 100 Talents Programme of the
Chinese Academy of Sciences. We thank Prof. Daqiang Yuan
(Fujian Institute of Research on the Structure of Matter,
Chinese Academy of Sciences) for his kind help in an X-ray
analysis.
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Enantioselective Synthesis of trans-Vicinal Diamines via
Rhodium-Catalyzed [2+2] Cycloaddition of Allena-
mides
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