Article Cite This: J. Am. Chem. Soc. 2018, 140, 3299−3305
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Chiral Nickel(II) Complex Catalyzed Enantioselective Doyle−Kirmse Reaction of α‑Diazo Pyrazoleamides Xiaobin Lin,† Yu Tang,† Wei Yang,† Fei Tan,† Lili Lin,† Xiaohua Liu,*,† and Xiaoming Feng*,†,‡ †
Key Laboratory of Green Chemistry & Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, China ‡ Collaborative Innovation Center of Chemical Science and Engineering, Tianjin 300072, China S Supporting Information *
ABSTRACT: Although high enantioselectivity of [2,3]-sigmatropic rearrangement of sulfonium ylides (Doyle−Kirmse reaction) has proven surprisingly elusive using classic chiral Rh(II) and Cu(I) catalysts, in principle it is due to the difficulty in fine discrimination of the heterotopic lone pairs of sulfur and chirality inversion at sulfur of sulfonium ylides. Here, we show that the synergistic merger of new α-diazo pyrazoleamides and a chiral N,N′-dioxide-nickel(II) complex catalyst enables a highly enantioselective Doyle−Kirmse reaction. The pyrazoleamide substituent serves as both an activating and a directing group for the ready formation of a metal-carbene- and Lewis-acid-bonded ylide intermediate in the assistance of a dual-tasking nickel(II) complex. An alternative chiral Lewis-acid-bonded ylide pathway greatly improves the product enantiopurity even for the reaction of a symmetric diallylsulfane. The majority of transformations over a series of aryl- or vinyl-substituted α-diazo pyrazoleamindes and sulfides proceed rapidly (within 5−20 min in most cases) with excellent results (up to 99% yield and 96% ee), providing a breakthrough in enantioselective Doyle−Kirmse reaction.
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INTRODUCTION The [2,3]-sigmatropic rearrangement of sulfonium ylides (known as the Doyle−Kirmse reaction) was discovered by Kirmse in 19681 and modified by Doyle in 1981.2 The reaction involving allylic or propargylic sulfides and diazo reagents represents an important method to construct new C−C and C(sp3)−S bonds with an allyl- or allenyl-substituted stereogenic center.3 The asymmetric catalytic version has attracted considerable attention since the initial attempt by Uemura and co-workers in 1995,4 but remains particularly challenging at present. In previous reports, the metal-carbenes are typically generated in situ from diazo precursors with various transition metal salts, such as Cu(I), Rh(II), Co(III), and Fe(II) (Scheme 1a).3−8 For instance, chiral bisoxazoline-Cu(I) catalysts and the Doyle catalysts have been optimized to promote the enantioselective rearrangement of allylic arylsulfides by several research groups,6a−e but moderate enantioselectivity (78% ee) is the highest result.6c Likewise, a chiral salen-Co(III) complex5 and the myoglobin variant Mb(L29S,H64V,V68F) were identified with average enantioselection.8 Recently, the Wang group made a breakthrough in asymmetric trifluoromethylthiolation through chiral Rh(II) and Cu(I) catalyst-promoted rearrangement of SCF3-containing sulfonium ylides.7 In principle, the chiral transition metal complex catalyzed asymmetric Doyle−Kirmse reaction can follow two possible routes (Scheme 1a).3 Initially, a metal-carbene complex is generated by decomposition of a diazo compound with a chiral transition metal catalyst, which then reacts with allylic sulfide via discrimination of its heterotopic lone pairs to form sulfonium ylides selectively. If the chiral catalyst is bonded © 2018 American Chemical Society
with an ylide during the rearrangement, the chiral catalyst may further direct the enantioselective allyl shift. Otherwise, if the chiral catalyst is released, the free nonracemic ylide may retain the chirality during the rearrangement due to the fact that the rearrangement occurs by a concerted mechanism via an envelope transition state.3−5,6a,b,7 The latter was evidenced by the experiment of Trost and Hammen in which a chiral sulfonium ylide generated from deprotonation of an optically pure sulfonium salt could undergo [2,3]-sigmatropic rearrangement to yield a product with 94% ee (Scheme 1b).9 Nevertheless, in fact three issues will affect the stereochemistry of this type of rearrangement. One is that it is difficult to finely discriminate the heterotopic lone pairs of sulfur with a chiral metal complex. Second, the chiral metal-bonded ylide is in equilibrium with the free ylide and the free ylide is more likely to undergo the following rearrangement.3c−i,10 Solid evidence of these is that a nearly racemic product was generated from chiral Rh(II)- and Cu(I)-catalyzed reaction of diallylsulfane (Scheme 1c).6c,7 In addition, if the inversion at sulfur of the free nonracemic ylide is much faster than sigmatropic rearrangement, enantioselectivity of the reaction is thus poor. For all these reasons, further development of novel approaches to achieving a highly enantioselective Doyle−Kirmse reaction is highly desirable and challenging. Our strategy toward enantioselective Doyle−Kirmse reaction stems from development of new α-diazo carbonyl compounds and employment of a novel dual-tasking chiral metal complex Received: November 26, 2017 Published: February 14, 2018 3299
DOI: 10.1021/jacs.7b12486 J. Am. Chem. Soc. 2018, 140, 3299−3305
Journal of the American Chemical Society
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Scheme 1. Strategy for the Catalytic Asymmetric Doyle− Kirmse Reaction
Article
RESULTS AND DISCUSSION
As a suitable substrate for our purpose, we opted for the use of donor−acceptor diazo compound 1a bearing a 3,5-dimethyl1H-pyrazolyl substituent with allyl(phenyl)sulfane 2a to identify an appropriate chiral catalyst (Table 1; see Supporting Information for details). Initially, chiral N,N′-dioxide L3-PiPr2 synthesized from L-pipecolic acid and 2,6-diisopropylaniline was used to recognize the metal salts. Rare-earth metal salts, such as Sc(OTf)3 and Yb(OTf)3, which showed excellent performance with chiral N,N′-dioxide ligands in several asymmetric catalytic reactions of α,β-unsaturated pyrazoleamides, were ineffective in this case (entry 1).11e−g,12,13 Thus, thermal- and Lewis acidactivated decomposition of the α-diazo pyrazoleamide into a carbene at this condition was excluded. We next evaluated metal salts used for both metallocarbene formation and Lewis acid activation (entries 2−8). We examined Rh(II), Ag(I), Cu(I), Fe(II), and Ni(II) as the metal ions, and one exception was Rh2(OAc)4, which led to the gradual decomposition of the diazo substrate but none of the desired product (entry 2), with a completely different capability for the reaction of the αdiazoester.13 The same result was observed with the AgOTf system (entry 3). With copper salts, the rearrangement product 3a was detected with varied yields along with the counterions, but the enantioselectivities were poor (entries 4−6). Interestingly, the use of Fe(OTf)2 and Ni(OTf)2 led to the formation of 3a with increased results (entries 7 and 8). In the instance of Ni(OTf)2, the yield and ee were slightly higher compared to when Fe(OTf)2 was adopted (88% yield and 64% ee within 1 h compared to 66% yield and 56% ee within 10 h). This is particularly noteworthy since nickel catalysts capable of forming carbenes are rare,14,15 much less a catalytic asymmetric version. With regard to the choice of chiral ligands, to maximize the interaction of the α-diazo compound 1a with the Ni(II) species, we chose to optimize N,N′-dioxides with varied amino acid backbones (entries 9 and 10), carbon linkers (entry 11), and amide units (entry 12). The N,N′-dioxide L2-PiPr2-Ni(OTf)2 catalyst favored the asymmetric Doyle−Kirmse reaction of 1a with high activity and enantioselectivity over others, forming the product 3a in 86% yield and 87% ee within 15 min (entry 11). Additionally, there is an obvious ligand-accelerating effect because only a trace amount of the product was detected without the chiral L2-PiPr2 ligand (entry 13). Subsequently, we studied the effect of solvent and temperature (entries 14−17). The yields and enantioselectivities decreased obviously when the reactions were performed in tetrahydrofuran (THF) or EtOAc, as well as with a reaction temperature at 20 °C. To our delight, the [2,3]-sigmatropic rearrangement reaction was conducted efficiently in 10 min at 40 °C with maintained results (entry 17). Meanwhile, when the diazo compound 1b, bearing a 3,4,5-trimethyl-1H-pyrazolyl group, was applied instead of 1a, and the corresponding product 3b was given in 84% yield with 90% ee (entry 18). Examination of coordinating counterions of the nickel(II) salt led to a slight increase in enantioselectivity but a decrease in yield if the mixture of NiCl2 and AgNTf2 was used instead of Ni(NTf2)2 and Ni(OTf)2 (entries 19 and 20). It was observed that AgNTf2 as an additive could improve the enantioselectivity of this reaction to some extent. Fortunately, the yield was fully compensated after the amount of diazo pyrazoleamide 1b increased to 1.15 equivalents, and a yield of 95% with 94% ee was given within 5 min (entry 21). Further reduction of catalyst loading resulted in a longer reaction time (10 min for 5 mol % and 3.5 h for 2.5
catalyst (Scheme 1d). We obtain a new donor−acceptor αdiazo compound 1 by introducing a pyrazoleamide group instead of an ester group in view of two points. The reactivity of the α-diazo compound could be defined by this electronwithdrawing substituent that adorns the related carbene intermediate. The pyrazoleamide group is an excellent functional unit that accepts a strong bidentate coordination to a Lewis acid.11 On the other hand, the choice of chiral catalyst must enable both the formation of a metal carbene and the stereocontrol in the sigmatropic rearrangement of sulfonium ylides via tight coordination. Therefore, the difficulties that lie in the asymmetric Doyle−Kirmse reaction will be addressed by a novel chiral Lewis-acid-bonded ylide process, regardless of the chirality of the sulfonium ylide and equilibrium of metal-bonded ylide. Encouraged by the applications of privileged N,N′-dioxide-metal complexes in asymmetric catalysis, which has been well studied in our group,11e−g,12 we envision that this kind of catalyst alone might govern the reaction between α-diazo pyrazoleamides and allyl arylsulfides, to a certain extent similar to the double asymmetric induction approach of Wang’s work by exploring a diazo substrate bearing a chiral auxiliary.6f Herein, we discover that the chiral N,N′-dioxide-Ni(II) complex shows great advantage in the asymmetric Doyle−Kirmse reaction of α-diazo pyrazoleamides. High yields and excellent enantioselectivities are achieved for a wide range of aryl- or vinyl-substituted αdiazo compounds and allylic sulfides within 5−20 min. The reaction of diallylsulfane is also highly enantioselective, which illustrates an unprecedented process in this instance. These results supported a dual-tasking chiral Ni(II) complex promoted asymmetric Doyle−Kirmse reaction via a new and useful Lewis-acid-bonded ylide route. 3300
DOI: 10.1021/jacs.7b12486 J. Am. Chem. Soc. 2018, 140, 3299−3305
Article
Journal of the American Chemical Society Table 1. Optimization of the Reaction Conditionsa
entry
1
metal salt(s)
ligand
T (°C)
time
solvent
yield (%)b
1 2d 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20e 21e,f 22f,g 23f,h 24e,i
1a 1a 1a 1a 1a 1a 1a 1a 1a 1a 1a 1a 1a 1a 1a 1a 1a 1b 1b 1b 1b 1b 1b 4a
Sc(OTf)3 or Yb(OTf)3 Rh2(OAc)4 AgOTf CuOTf·(C6H6)1/2 Cu(CH3CN)4PF6 CuCl Fe(OTf)2 Ni(OTf)2 Ni(OTf)2 Ni(OTf)2 Ni(OTf)2 Ni(OTf)2 Ni(OTf)2 Ni(OTf)2 Ni(OTf)2 Ni(OTf)2 Ni(OTf)2 Ni(OTf)2 Ni(NTf2)2 NiCl2 + AgNTf2 NiCl2 + AgNTf2 NiCl2 + AgNTf2 NiCl2 + AgNTf2 NiCl2 + AgNTf2
L3-PiPr2 L3-PiPr2 L3-PiPr2 L3-PiPr2 L3-PiPr2 L3-PiPr2 L3-PiPr2 L3-PiPr2 L3-PrPr2 L3-RaPr2 L2-PiPr2 L2-PiEt2 none L2-PiPr2 L2-PiPr2 L2-PiPr2 L2-PiPr2 L2-PiPr2 L2-PiPr2 L2-PiPr2 L2-PiPr2 L2-PiPr2 L2-PiPr2 L2-PiPr2
35 35 35 35 35 35 35 35 35 35 35 35 35 35 35 20 40 40 40 40 40 40 40 40
10 h 7h 10 h 0.5 h 0.5 h 2h 10 h 1h 1h 10 h 15 min 15 min 10 h 10 h 10 h 2h 10 min 10 min 5 min
