10.1002/chem.201804099
Chemistry - A European Journal
COMMUNICATION
Based on single crystal X-ray diffraction and NMR studies
providing evidence of complex formation between AgOAc and
N,P-ligand 1b,[8b] we performed a computational analysis of
competing transition structures (TSs) (Figure 2). Since N-DPP
Keywords: Mannich reaction • isocyanides • addition to
ketimines • silver • homogeneous catalysis
[1]
[2]
[3]
[4]
Chiral Amine Synthesis: Methods, Developments and Applications (Ed.:
T. C. Nugent), Wiley, Weinheim, 2010.
ketimines exist as
a mixture of E- and Z-configurated
stereoisomers rapidly interconverting at room temperature,[19] we
examined both configurations computationally. In the most
stable TSs the imine adopts an E-configuration, which is favored
sterically. In addition to N,P-coordination of silver, the ligand
plays a role in substrate activation during C-C bond formation:
the phosphinoyl oxygen was found to coordinate to the amide N-
H proton in addition to Ag in each of the most stable TSs (Fig. 2).
The major TS is perfectly staggered about the forming C-C bond,
whereas steric interactions between the quinuclidine region of
the ligand and the ketimine phenyl group result in a less-stable,
eclipsed, TS forming the minor enantiomer (G‡ 2.3 kcal/mol).
S. France, D. J. Guerin, S. J. Miller, T. Lectka, Chem. Rev. 2003, 103,
2985–3012.
A. K. Mailyan, J. A. Eickhoff, A. S. Minakova, Z. Gu, P. Lu, A. Zakarian,
Chem. Rev. 2016, 116, 4441–4557.
For reviews on catalytic enantioselective additions to C=N bonds, see
(a) A. Cordova, Acc. Chem. Res. 2004, 37, 102–112; (b) G. K. Friestad,
A. K. Mathies, Tetrahedron 2007, 63, 2541–2569; (c) D. Ferraris,
Tetrahedron 2007, 63, 9581–9597; (d) O. Riant, J. Hannedouche, Org.
Biomol. Chem. 2007, 5, 873–888; (e) M. Shibasaki, M. Kanai, Chem.
Rev. 2008, 108, 2853–2873; (f) K. Yamada, K. Tomioka, Chem. Rev.
2008, 108, 2874–2886; (g) S. Kobayashi, Y. Mori, J. S. Fossey, M. W.
Salter, Chem. Rev. 2011, 111, 2626–2704; (h) M. Yus, J. C. González-
Gómez, F. Foubelo, Chem. Rev. 2011, 111, 7774–7854; (i) Science of
Synthesis: Stereoselective Synthesis 2: Stereoselective Reactions of
Carbonyl and Imino Groups, (Vol. Ed.: G. A. Molander), Thieme,
Stuttgart, 2011; (j) T. Akiyama, in Comprehensive Organic Synthesis,
(Ed.: P. Knochel and G. A. Molander), Elsevier, Oxford, 2nd edn, 2014,
vol. 2, p. 629; (k) N. Kumagai, M. Shibasaki, Bull. Chem. Soc. Jpn.
2015, 88, 503–517.
[5]
For selected examples of catalytic enantioselective additions to
ketimines, see: (a) P. Vachal, E. N. Jacobsen, J. Am. Chem. Soc. 2002,
124, 10012–10014; (b) W. Zhuang, S. Saaby, K. A. Jørgensen, Angew.
Chem. Int. Ed. 2004, 43, 4476–4478; Angew. Chem. 2004, 116, 4576–
4578; (c) Y. Suto, M. Kanai, M. Shibasaki, J. Am. Chem. Soc. 2007,
129, 500–501; (d) C. Tan, X. Liu, L. Wang, J. Wang, X. Feng, Org. Lett.
2008, 10, 5305–5308; (e) T. Kano, S. Song, Y. Kubota, K. Maruoka,
Angew. Chem. Int. Ed. 2012, 51, 1191–1194; Angew. Chem. 2012, 124,
1217–1220; (f) T. Nishimura, A. Noishiki, G. C. Tsui, T. Hayashi, J. Am.
Chem. Soc. 2012, 134, 5056–5059; (g) S. Nakamura, S. Takahashi, D.
Nakane, H. Masuda, Org. Lett. 2015, 17, 106–109; (h) H. Jang, F.
Romiti, S. Torker, A. H. Hoveyda, Nat. Chem. 2017, 9, 1269–1275; (i) P.
Ortiz, J. F. Collados, R. P. Jumde, E. Otten, S. R. Harutyunyan, Angew.
Chem. Int. Ed. 2017, 56, 3041–3044; Angew. Chem. 2017, 129, 3087–
3090.
Figure 2. Competing C-C forming TSs for major and minor enantiomers for
the reaction between acetophenone-derived N-DPP ketimine and TosMIC
(SMD-M06/6-311++G(d,p)//ONIOM(M06/def2-SVP:UFF).
In summary, we have developed the first enantioselective
addition of the versatile, commercially available p-
toluenesulfonylmethyl isocyanide to ketimines, by using a
Ag(I)/amino phosphine catalytic system. The reaction afforded 2-
imidazolines with high yields and excellent diastereo- and
enantiocontrol, which could be elaborated to vicinal diamines,
precursors to NHC ligands and heterocyclic scaffolds such as
2,5-dihydropyrazines. The transformation was broad in scope,
encompassing several (hetero)aromatic and aliphatic ketimines,
operationally simple and scalable. Computations reveal a
bifunctional catalyst with Ag and N-H groups activating the
electrophile, and rationalize the experimental stereoselectivity.
[6]
[7]
[8]
F. Sladojevich, A. Trabocchi, A. Guarna and D. J. Dixon, J. Am. Chem.
Soc. 2011, 133, 1710–1713.
R. de la Campa, I. Ortín, D. J. Dixon, Angew. Chem. Int. Ed. 2015, 54,
4895; Angew. Chem. 2015, 127, 4977–4980.
a) I. Ortín, D. J. Dixon, Angew. Chem. Int. Ed. 2014, 53, 3462–3465;
Angew. Chem. 2014, 126, 3530–3533; b) R. de la Campa, A. D.
Gammack Yamagata, I. Ortín, A. Franchino, A. L. Thompson, B. Odell,
D. J. Dixon, Chem. Commun. 2016, 52, 10632–10635.
[9]
M. Giustiniano, A. Basso, V. Mercalli, A. Massarotti, E. Novellino, G. C.
Tron, J. Zhu, Chem. Soc. Rev. 2017, 46, 1295–1357.
[10] a) D. Van Leusen, A. M. van Leusen, Org. React. 2001, 57, 417–666;
b) T. Kaur, P. Wadhwa, A. Sharma, RSC Adv. 2015, 5, 52769–52787.
[11] a) M. Sawamura, H. Hamashima, Y. Ito, J. Org. Chem. 1990, 55, 5935–
5936; b) Y. Motoyama, H. Kawakami, K. Shimozono, K. Aoki, H.
Nishiyama, Organometallics 2002, 21, 3408–3416; c) A. R. Keeri, A.
Gualandi, A. Mazzanti, J. Lewinski, P. G. Cozzi, Chem. Eur. J. 2015, 21,
18949–18952.
Acknowledgements
The authors thank the European Union for funding (PhD
fellowship to A.F., FP7/2007–2013, 316955) and Severo Ochoa
(predoctoral training fellowship to I. F.-A., SVP-2014- 0686662).
We thank Dr Adam D. Gammack Yamagata for useful
discussion, Heyao Shi and Dr. Angel Fuentes de Arriba for X-ray
analysis and the Oxford Chemical Crystallography Service for
use of their instrumentation. This work used the RMACC Summit
cluster (NSF ACI-1532235 and ACI-1532236), supported by the
University of Colorado Boulder and Colorado State University.
[12] Cyclodimerization of TosMIC under basic conditions was already
observed: O. H. Oldenziel, D. Van Leusen, A. M. van Leusen, J. Org.
Chem. 1977, 42, 3114–3118.
[13] TosMIC analogues possessing a methyl, ethyl or phenyl group in the α
position were not competent pronucleophiles due to a competitive and
dominant cyclodimerization reaction (see SI). Ketimines possessing an
aldehyde or ketone functional group on the aromatic ring are expected
to undergo competitive oxazoline formation (see references 6, 7 and
11). A nitro group on the aromatic ring of the ketimine may also
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