A facile Pd(0)-catalyzed regie- and stereoselective diamination of conjugated dienes and trienes

Article abstract of DOI:10.1021/ja0680562

This paper describes a novel diamination process using di-t-butyldiaziridinone as the nitrogen source and Pd(PPh₃)₄ as catalyst. A wide variety of conjugated dienes and trienes can be effectively diaminated in good yields with high r

Full text of DOI:10.1021/ja0680562

Published on Web 01/04/2007
A Facile Pd(0)-Catalyzed Regio- and Stereoselective Diamination of
Conjugated Dienes and Trienes
Haifeng Du, Baoguo Zhao, and Yian Shi*
Department of Chemistry, Colorado State UniVersity, Fort Collins, Colorado 80523
Received November 10, 2006; E-mail: yian@lamar.colostate.edu
Table 1. Catalytic Diamination of Dienes and Trienesa
Vicinal diamines are very important functional moieties which
are present in various biologically active compounds and have also
been widely used as chiral control elements in asymmetric
synthesis.1 Diamination of olefins presents an attractive strategy
for the synthesis of vicinal diamines. Various metal-free1,2 or metal-
mediated1,3,4 processes have been developed. Metal-catalyzed
diaminations have also been reported.5,6 Very recently, it has been
shown that both intermolecular diamination of conjugated dienes6a
and intramolecular6b diamination of terminal olefins with ureas can
be achieved using Pd(II) as catalyst. For the intermolecular process,
the diamination occurred regioselectively at less-substituted double
bonds of dienes. In these cases, the amination is likely to proceed
via a Pd(II)-promoted aza-Wacker-type process (trans-amino-
palladation),3g,6,7 followed by the replacement of the C-Pd bond
with a C-N bond.3g,6,7
As part of our general interest in synthetic transformations of
dioxirane8 and its nitrogen analogues, we have been exploring a
possible metal-catalyzed diamination of olefins via an oxidative
addition to the N-N bond of diaziridine 1 to form diamido species
2, followed by a migratory insertion to a double bond to form 39
and a subsequent reductive elimination to form 4 (Scheme 1).
Herein we wish to report our preliminary efforts on this subject.
The diamination was examined with olefins and di-t-butyldi-
aziridinone (6)10,11 using Pd(PPh3)4 as catalyst. Among the olefins
tested, conjugated dienes were found to be very effective substrates
(Scheme 2). For example, subjecting trans-1,3-pentadiene (5a) to
the reaction conditions (Scheme 2) for 30 min led to a clean
diamination product (7a) in 94% yield (Table 1, entry 1). The
reaction occurred highly regioselectively at the internal double bond
and highly stereoselectively as well.12 As shown in Table 1, this
diamination can be extended to a variety of dienes including both
electron-rich (Table 1, entries 8 and 9) and electron-deficient dienes
(Table 1, entry 10). Trisubstituted double bonds can also be
diaminated (Table 1, entries 11-13). When a conjugated triene was
used, the diamination occurred cleanly at the middle double bond
(Table 1, entries 14-15). In all these cases (Table 1, entries 1-15),
essentially only one regio- and stereoisomer was obtained.12 It
appears that only trans- and trisubstituted double bonds react under
the reaction conditions. For example, no diamination was observed
when cis-1,3-pentadiene was used. Therefore, when a mixture of
a All reactions were carried out with di-t-butyldiaziridinone (6) (0.2
E and Z dienes were used (Table 1, entries 2, 7, and 11), only the
mmol), diene or triene (0.24 mmol, 1.2 equiv), and Pd(PPh3)4 (0.02 mmol)
in benzene-d6 (0.6 mL) in an NMR tube at 65 °C under argon unless
E isomer reacted and the Z isomer was enriched after the reaction.
otherwise stated. b A mixture of E and Z isomers was used. For entry 2,
diene (0.53 mmol, E/Z ) 1/1.2, E isomer: 0.24 mmol); for entry 7, diene
(0.48 mmol, E/Z ) 1/1, E isomer: 0.24 mmol); for entry 11, diene (0.34
mmol, E/Z ) 2.5/1, E isomer: 0.24 mmol). c Containing <10% Z isomer.
d Compounds are acid sensitive and were purified on less acidic silica gel
(Iatrobeads 6RS-8060, Mitsubishi Kagaku Iatron, Inc. Japan). e Isolated yield
based on 6.
The diamination also occurred for the dienes containing geminal
disubstituted double bonds (Table 1, entries 16 and 17). In these
two cases, the reaction occurred also regioselectively and stereo-
selectively.13 The stereochemistry of the diamination products (7)
was tentatively assigned by comparing the NOE of compounds 7b,
g, h, and p (Table 1, entries 2, 7, 8, and 16) with 7q (Table 1,
entry 17) (see Supporting Information). The X-ray structure of
compound 7n (Table 1, entry 14) further supports the assigned
stereochemistry (Scheme 3).
The deprotection of compound 7b (Table 1, entry 2) was
investigated. Treating 7b with CF3CO2H (TFA) at 75-80 °C for 2
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10.1021/ja0680562 CCC: $37.00 © 2007 American Chemical Society

C O M M U N I C A T I O N S
Scheme 1
Scheme 2
diamination products in good yields with high regio- and stereo-
selectivities. This Pd(0)-catalyzed diamination is mechanistically
distinct from the Pd(II)-catalyzed process, thus resulting in different
regioselectivity.6 Further studies of the reaction mechanism,
development of a more effective catalytic process with different
nitrogen sources and metal catalysts, and expansion of the substrate
scope as well as the asymmetric process are currently underway.
Acknowledgment. We are grateful to the generous financial
support from the Monfort Foundation (CSU).
Supporting Information Available: The diamination and depro-
tection procedures, the characterization of diamination products, and
the X-ray data of compounds 7n and 9a. This material is available
free of charge via the Internet at http://pubs.acs.org.
Scheme 3. The X-ray Structures of Compounds 7n and 9a
References
(1) For leading reviews, see: (a) Lucet, D.; Gall, T. L.; Mioskowski, C. Angew.
Chem., Int. Ed. 1998, 37, 2580. (b) Mortensen, M. S.; O’Doherty, G. A.
Chemtracts: Org. Chem. 2005, 18, 555. (c) Kotti, S. R. S. S.; Timmons,
C.; Li, G. Chem. Biol. Drug Des. 2006, 67, 101.
(2) For leading references on recent Ritter-type diamination see: (a) Li, G.;
Kim, S. H.; Wei, H-X. Tetrahedron Lett. 2000, 41, 8699. (b) Booker-
Milbum, K. I.; Guly, D. J.; Cox, B.; Procopiou, P. A. Org. Lett. 2003, 5,
3313.
Scheme 4
(3) For examples of metal-mediated diaminations, see the following. Co: (a)
Becker, P. N.; White, M. A.; Bergman, R. G. J. Am. Chem. Soc. 1980,
102, 5676. Hg: (b) Barluenga, J.; Alonso-Cires, L.; Asensio, G. Synthesis
1979, 962. Mn: (c) Fristad, W. E.; Brandvold, T. A.; Peterson, J. R.;
Thompson, S. R. J. Org. Chem. 1985, 50, 3647. Os: (d) Chong, A. O.;
Oshima, K.; Sharpless, K. B. J. Am. Chem. Soc. 1977, 99, 3420. (e) Mun˜iz,
K.; Nieger, M. Synlett 2003, 211. (f) Mun˜iz, K.; Nieger, M. Chem.
Commun. 2005, 2729. Pd: (g) Ba¨ckvall, J.-E. Tetrahedron Lett. 1978,
163. Tl: (h) Aranda, V. G.; Barluenga, J.; Aznar, F. Synthesis 1974, 504.
(4) For a recent Cu(II)-mediated intramolecular diamination, see: Zabawa,
T. P.; Kasi, D.; Chemler, S. R. J. Am. Chem. Soc. 2005, 127, 11250.
(5) For Rh(II) and Fe(III)-catalyzed diamination with TsNCl2 see: (a) Li,
G.; Wei, H.-X.; Kim, S. H.; Carducci, M. D. Angew. Chem., Int. Ed. 2001,
40, 4277. (b) Wei, H.-X.; Kim, S. H.; Li, G. J. Org. Chem. 2002, 67,
4777.
Scheme 5. A Proposed Catalytic Cycle for Diamination
(6) (a) Bar, G. L. J.; Lloyd-Jones, G. C.; Booker-Milbun, K. I. J. Am. Chem.
Soc. 2005, 127, 7308. (b) Streuff, J.; Ho¨velmann, C. H.; Nieger, M.;
Mun˜iz, K. J. Am. Chem. Soc. 2005, 127, 14586.
(7) For leading reviews, see: (a) Hegedus, L. S. Tetrahedron 1984, 40, 2415.
(b) Mu¨ller, T. E.; Beller, M. Chem. ReV. 1998, 98, 675.
(8) Shi, Y. Acc. Chem. Res. 2004, 37, 488.
(9) For examples of less common cis-aminopalladation, see: (a) Isomura,
K.; Okada, N.; Saruwatari, M.; Yamasaki, H.; Taniguchi, H.; Chem. Lett.
1985, 385. (b) Ney, J. E.; Wolfe, J. P. Angew. Chem. Int. Ed. 2004, 43,
3605. (c) Brice, J. L.; Harang, J. E.; Timokhin, V. I.; Anastasi, N. R.;
Stahl, S. S. J. Am. Chem. Soc. 2005, 127, 2868. (d) Liu, G.; Stahl, S. S.
J. Am. Chem. Soc. 2006, 128, 7179.
h gave a clean deprotection product 8 in 98% yield (Scheme 4).
Interestingly, monodeprotection was also possible when the reaction
was carried out at room temperature, giving 9a as major product
(Scheme 4). The structure of 9a was determined by X-ray (Scheme
3). The selective monodeprotection provides opportunities to
introduce different groups on the two nitrogens if it is desired.
While a precise reaction mechanism awaits further study, a
plausible catalytic cycle is shown in Scheme 5. The Pd(0) first
inserts into the N-N bond of diaziridinone 6 to form a four-
membered Pd(II) species (10).14 Upon complexing with diene 5
and a migratory insertion, compound 10 is then converted into
π-allyl Pd complex 12,15 which then undergoes a reductive
elimination to form product 7 and regenerate the Pd(0) catalyst.16
In summary, a diamination for a variety of conjugated dienes
and trienes has been effectively achieved using di-t-butyldiaziri-
dinone as the nitrogen source and Pd(PPh3)4 as catalyst, giving the
(10) Prepared on the basis of the reported method: Greene, F. D.; Stowell, J.
C.; Bergmark, W. R. J. Org. Chem. 1969, 34, 2254.
(11) For a leading review on diaziridinones, see: Heine, H. W. In The
Chemistry of Heterocyclic Compounds; Hassner, A., Ed.; John Wiley &
Sons, Inc: New York, 1983; pp 547.
(12) Other regio- and stereoisomers were barely detectable by 1H NMR of the
crude reaction mixture if there was any.
(13) When isoprene was used, however, a mixture of two regioisomers (2.3:
1) was formed in 90% yield after 1 h reaction. The diamination slightly
preferred the more substituted double bond in this case.
(14) The insertion of Ni and Pd to the N-N bond of diaziridinone has been
reported, see: Komatsu, M.; Tamabuchi, S.; Minakata, S.; Ohshiro, Y.
Heterocycles 1999, 50, 67. However, to the best our knowledge, the
reaction of the resulting complex 10 with an olefin has not been reported.
(15) For a recent leading review on π-allyl Pd chemistry, see: Trost, B. M. J.
Org. Chem. 2004, 69, 5813.
(16) For a recent book, see: Tsuji, J. Palladium Reagents and Catalysts: New
PerspectiVe for the 21st Century; John Wiley & Sons Ltd: New York,
2004.
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