Letter pubs.acs.org/OrgLett
Cite This: Org. Lett. 2018, 20, 2485−2489
Pd(II)-Catalyzed Asymmetric Oxidative 1,2-Diamination of Conjugated Dienes with Ureas Min-Song Wu,† Tao Fan,† Shu-Sen Chen,† Zhi-Yong Han,*,† and Liu-Zhu Gong*,†,‡ †
Hefei National Laboratory for Physical Sciences at the Microscale and Department of Chemistry, University of Science and Technology of China, Hefei 230026, China ‡ Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, China S Supporting Information *
ABSTRACT: A palladium(II)-catalyzed asymmetric 1,2-diamination of 1,3-dienes with readily available dialkylureas was established by using a chiral pyridine−oxazoline ligand. The diamination reaction exclusively occurs at the terminal C−C double bond of the 1,3-dienes to give 4-vinylimidazolidin-2-ones in high yields and with excellent levels of enantioselectivity (up to 99% yield, 97% ee). The reaction could feasibly be applied for gram-scale synthesis with a 1:1 ratio of the diene and the urea.
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the diamination reagents require multistep synthesis and are limited to N-tert-butyl compounds. Muñiz established a Ticatalyzed, asymmetric intermolecular diamination of alkenes by using stoichiometric amounts of osmium reagents.7 Very recently, an iodine(I/III)-catalyzed enantioselective intramolecular diamination of styrenes using ditosylamide as the amination source was described by Muñiz and co-workers.8 An appealing alternative is Pd(II)-catalyzed Wacker-type oxidative diamination of conjugated dienes using readily available diamination sources, such as ureas.9 The reaction was believed to proceed starting with a Pd(II)-catalyzed azaWacker-type process and followed by an intramolecular allylation.10,11 The racemic reaction was realized with Pd(MeCN)2Cl2 as the catalyst without an extra ligand to remain the activity of the catalyst in the aza-Wacker step by LloydJones and Booker-Milburn. 12 To render the reaction enantioselective, the chiral Pd(II) should act as a “dual-role” catalyst, being efficient in both the aza-Wacker-type process and the asymmetric allylation step. These two roles are somewhat contradictory since the existence of ligands usually renders the palladium catalyst less nucleophilic and, thus, makes the azaWacker step sluggish. As such, although the racemic reaction based on this concept has long been reported,12 an asymmetric variant has remained unestablished in the past decade. As a continuation of our research in “dual-role” chiral palladium(II) catalysis,13 we will present our efforts to accomplish the Pd(II)catalyzed asymmetric 1,2-diamination reaction of 1,3-dienes with ureas (Figure 1b). Our investigation was initially focused on seeking suitable chiral ligands for the Pd(II)-catalyzed diamination reaction of (E)-1-phenylbutadiene (1a) and 1,3-diethylurea (2a) (Table
icinal diamines are not only important structural motifs frequently encountered in a number of natural products and bioactive compounds but also for privileged chiral elements in asymmetric catalysis.1 Transition-metal-catalyzed 1,2-diamination of alkenes represents one of the most straightforward and convenient approaches toward these structures.2 While metal-catalyzed, nonasymmetric 1,2-diamination has been intensively explored in recent decades,2,3 the asymmetric variants have remained largely limited to intramolecular reactions4 with very few exceptions. While Sharpless asymmetric dihydroxylation and aminohydroxylation could be performed in a catalytic manner, the related asymmetric diamination requires stoichmetric usage of the osmium metal. Notable examples for metal-catalyzed intermolecular asymmetric diamination include Shi’s works on chiral Pd(0)-catalyzed asymmetric 1,2-diamination of 1,3-dienes using di-tert-butyldiaziridinone or di-tert-butylthiadiaziridine 1,1-dioxide as the nitrogen source, basically leading to 3,4-diamination products with high enantioselectivities (Figure 1a).5,6 Although these methods are very useful and tolerate a large array of substrates,
Figure 1. Pd-catalyzed intermolecular asymmetric diamination of 1,3dienes. © 2018 American Chemical Society
Received: March 17, 2018 Published: April 3, 2018 2485
DOI: 10.1021/acs.orglett.8b00870 Org. Lett. 2018, 20, 2485−2489
Letter
Organic Letters 1). In the presence of 10 mol % of Pd(OTs)2(MeCN)214 with 2,5-dimethyl-1,4-benzoquinone as the oxidant, the diamination
substantially slow reaction (entry 10). Then, we tended to pay attention to pyridine oxazoline (pyrox) ligands bearing electron-withdrawing groups, inspired by their successful applications in palladium(II)-catalyzed transformations.17 Gratifyingly, while tert-butyl-substituted pyrox L10 provided low yield and enantioselectivity, the use of phenyl-substituted ligand L11 resulted in a highly active catalyst and gave the product with 81% yield and 73% ee (entry 12). Switching the CF3 group in L11 to other electron-withdrawing groups, e.g., a nitro group, led to a diminished yield and enantioselectivity (entry 13). A widespread evaluation of solvents discerned that tetrahydrofuran was the optimal media for the reaction (see the Supporting Information (SI) for details). We next examined the effect of the oxidant on the diamination reaction. It turned out that the oxidant had considerable influence on both the yield and enantioselectivity. In the presence of quinone-type oxidants (entries 14 and 15), though the yields varied dramatically, similar levels of enantioselectivity compared to DMBQ were observed. Interestingly, when oxygen was used as the oxidant, the optical selectivity dropped drastically (entry 16). This observation implied that the quinone or the corresponding hydroquinone should be involved in the asymmetric allylation step. Next, we found that the addition of of 5 Å molecular sieves could considerably improve the yield and enantioselectivity (entry 17). This effect might be attributed to an improved catalyst stability in the presence of molecular sieves17f,18 and the suppression of the Wacker reaction of the alkene and water.12 Increasing the loading of 1a and the ligand was found to be beneficial for the reaction (entries 18−20). Finally, prolonging the reaction time provided the product 3a with 99% yield and 89% ee (entry 21). Lowering the amount of 1a led to slight drop of the yield (entries 22−23). The optimal conditions were first applied to the reactions of a variety of dialkylureas with 1,3-diene 1a (Scheme 1, 3b−g). Most of the ureas reacted smoothly to give the corresponding diamination products in good yields and high levels of enantioselectivity (87−93% ee), a general trend could be observed that the bulkier alkyl substituent led to a higher enantioselectivity but lower reactivity (3d, 3g vs 3b, 3c). Dibenzylurea provided a product 3f with surprisingly low yield, presumably due to the decomposition of the substrate by benzylic oxidation. Diisopropylurea was found to be the best diamination reagent in terms of yield and enantioselectivity. It is worth noting that, in all these cases, the diamination proceeded at the terminal C−C double bond, without observation of other regioisomers. As such, the current method is highly complementary to Shi’s asymmetric diamination process, which usually occurs at the internal double bond.5a,d Next, various arylbutadienes were examined in reactions with diisopropylurea (3h−s). The presence of either an electrondonating or -withdrawing substituent at the para position was nicely tolerated and highly regioselectively generated the corresponding 3,4-diamination products with high enantioselectivity (3h−l, 87−92% ee). Arylbutadienes bearing strong electron-withdrawing groups, i.e., fluoro and trifluoromethyl groups, had low reactivity and, thus, required prolonged reaction time to reach satisfying yields (3i and 3l). Meta- and ortho-substituted arylbutadienes, including both electron-rich (3m, 3o and 3p) and electron-deficient ones (3n, 3q, and 3r), all underwent the reaction cleanly, giving the diamination products in good yields and excellent enantioselectivities (90− 97% ee). Moreover, the 2-naphthyl substrate was also tolerated,
Table 1. Optimization of Reaction Conditionsa
entry
L*
1 2 3 4 5 6 7 8 9 10 11 12 13 14d 15e 16f 17 18 19g 20h 21h 22h 23h
L1 L2 L3 L4 L5 L6 L7 L8 L9 L10 L11 L12 L11 L11 L11 L11 L11 L11 L11 L11 L11 L11
additive
1a/2a
time (h)
yieldb (%)
5 5 5 5 5 5 5
1/1.5 1/1.5 1/1.5 1/1.5 1/1.5 1/1.5 1/1.5 1/1.5 1/1.5 1/1.5 1/1.5 1/1.5 1/1.5 1/1.5 1/1.5 1/1.5 3/1 3/1 3/1 3/1 3/1 1.5/1 1/1
15 15 15 15 15 15 15 15 15 15 15 15 15 15 15 15 15 15 15 15 40 40 40
74 35 20 57 57 trace
