Lewis Acid Catalyzed Regioselective Addition of 1,3

Jun 7, 2017 - College of Materials Science and Engineering, Fujian Normal University, 8 Shangsan Road, Fuzhou 350007 People's Republic of China ...
0 downloads 11 Views 947KB Size
Download PDF
Article pubs.acs.org/Organometallics

Rhodium/Lewis Acid Catalyzed Regioselective Addition of 1,3Dicarbonyl Compounds to Internal Alkynes Wei-Feng Zheng,†,‡ Qiu-Jing Xu,† and Qiang Kang*,‡ ‡

Key Laboratory of Coal to Ethylene Glycol and Its Related Technology, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, 155 Yangqiao Road West, Fuzhou 350002, People’s Republic of China † College of Materials Science and Engineering, Fujian Normal University, 8 Shangsan Road, Fuzhou 350007 People’s Republic of China S Supporting Information *

ABSTRACT: Herein we describe an efficient protocol for the regioselective addition of 1,3-dicarbonyl compounds to internal alkynes catalyzed by rhodium/Lewis acid catalysts. The corresponding branched/linear allylic alkylation products could be selectively obtained in good yields. Rh−H species were considered to be generated by direct C−H oxidative addition of 1,3-dicarbonyl compounds with rhodium catalyst with the assistance of Lewis acid. Moreover, a retro-allylic alkylation process was observed in this transformation.

■

INTRODUCTION Transition-metal-catalyzed allylic alkylation reactions have flourished in the past few decades, which provide an efficient and powerful tool for constructing allylic C−C bonds.1−6 With the growing attention toward environmental issues, atomeconomical approaches have been welcomed by the synthetic community. Transition-metal-catalyzed addition of pronucleophiles to allenes or alkynes to form allylic C−X bonds (X = N, O, S) represents one of the most atom-economical approaches for the synthesis of allylic-substituted compounds. Following the pioneering work by Trost2a,f,7 and Yamamoto8 with palladium catalysts, the seminal work on regioselective hydrocarboxylation of allene catalyzed by iridium was realized by Krische in 2008.9 Recently, Breit and co-workers10−12 developed a series of rhodium-catalyzed pronucleophile addition reactions to allenes and terminal alkynes toward branched allylic products. In comparison to the formation of allylic C−X bonds, the formation of allylic C−C bonds has been less explored.13,14 For instance, the Breit and Dong groups have independently reported Rh-catalyzed decarboxylative cross-coupling of β-keto acids and allenes13a or alkynes13d,e to access branched γ,δunsaturated ketones (Scheme 1a). In these transformations, a substoichiometric amount of carboxylic acid was required as a cocatalyst15 for the generation of Rh−H species via oxidative addition of O−H in β-keto acids with an Rh complex. Previous reported works indicated that the presence of a more acidic O− H functional group in the pronucleophile or cocatalyst is necessary for formation of Rh−H species, which might narrow the substrate scope. Therefore, realizing direct C−H oxidative addition of carbon pronucleophiles with an Rh complex to generate a Rh−H species is an important task, which might enable more possible carbon pronucleophiles in such transformations. © XXXX American Chemical Society

Scheme 1. Rhodium-Catalyzed Allylic Alkylation Reactions

We speculated that a Lewis acid might increase the acidity of C−H bond of 1,3-dicarbonyl compounds to assist the oxidative addition with a Rh complex for the generation of the key Rh− H intermediate. Herein, we report our recent findings with a combination of rhodium and Lewis acid as catalyst to promote the regioselective addition of 1,3-dicarbonyl compounds to internal alkynes, which allowed access to either the branched or linear allylic-substituted products (Scheme 1b).

■

RESULTS AND DISCUSSION At the outset, acetylacetone (1a) and 1-phenyl-1-propyne (2a) were chosen as the model substrates to verify our hypothesis. In the presence of 5 mol % of [Rh(COD)OH]2, 12 mol % of dppf, and 6 mol % of Yb(OTf)3 in DCE at 70 °C, the reaction of 1a and 2 equiv of 2a proceeded smoothly to afford the branched Received: April 13, 2017

A

DOI: 10.1021/acs.organomet.7b00284 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics product 3a in 75% yield without observation of linear product 4a (entry 1, Table 1). However, only a trace amount of 3a was

Scheme 2. Reaction Substrate Scope: Alkynes

Table 1. Optimization of Reaction Conditionsa

entry

Rh(I)

L

Lewis acid

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15c 16d 17e

[Rh(COD)OH]2 [Rh(COD)OH]2

dppf dppf dppf dppf dppf dppf DPEphos Xanphos BINAP DPEphos DPEphos DPEphos DPEphos DPEphos DPEphos DPEphos DPEphos

Yb(OTf)3

[Rh(COD)Cl]2 [Rh(NBD)Cl]2 Rh(COD)2BF4 [Rh(COD)Cl]2 [Rh(COD)Cl]2 [Rh(COD)Cl]2 [Rh(COD)Cl]2 [Rh(COD)Cl]2 [Rh(COD)Cl]2 [Rh(COD)Cl]2 [Rh(COD)Cl]2 [Rh(COD)Cl]2 [Rh(COD)Cl]2 [Rh(COD)Cl]2

Yb(OTf)3 Yb(OTf)3 Yb(OTf)3 Yb(OTf)3 Yb(OTf)3 Yb(OTf)3 Yb(OTf)3 AlCl3 Gd(OTf)3 Bi(OTf)3 Sc(OTf)3 La(OTf)3 Yb(OTf)3 Yb(OTf)3 Yb(OTf)3

yieldb (%) 75 trace trace 96 40 6 99 1 79 0 87 34 20 22 20 88 79

3a/4a >95/5

>95/5 >95/5 >95/5 >95/5 >95/5 >95/5 >95/5 >95/5 >95/5 >95/5 >95/5 >95/5 90/10f 72/28f

allene, were also examined. In general, branched products with a terminal alkene were obtained for all of the alkynes tested. Substrates with phenethyl and a long alkyl chain led to moderate yields (3e,f). Benzylated and benzoylated alcohols were tolerated very well to afford 3g,h in 95% and 90% yields, respectively. A silylated alcohol gave a slightly low yield (76%, 3i), probably due to the instability of TBS under acidic conditions. A substrate with leaving group (OTs) had no significant effect on the outcome of the desired product 3j (80%). Even a free alcohol (2k) could be employed in this transformation, although a moderate yield was obtained. Alkynes with other sensitive functionalities such as chloride, keto, protected amine, and amide also worked well to afford the branched products in moderate to good yields (3l−o, 47− 97%). However, an aldehyde functionality could not be tolerated in such a transformation (3p, 0%). This approach also could be suitable for a complex substrate with a chiral skeleton, resulting in the corresponding branched alkylated product 3q in 87% yield.16 Notably, 1-phenyl-1-butyne (2r) exhibited good reactivity but poor regioselectivity, resulting in alkylated products 3r,r′ in 88% overall yield with almost 1/1 β/ δ selectivity. Next, various 1,3-dicarbonyl compounds were employed to investigate the generality of the current methodology. By employment of the optimal reaction conditions (entry 7, Table 1, conditions A), the reaction of ethyl-substituted 1,3-diketone 1b with 1-phenyl-1-propyne (2a) gave the alkylated products in 99% yield with 91/9 regioselectivity in favor of branched product 5a. Increasing the size of the 1,3-diketone only slightly affected the reactivity of the reaction (5b/6b 91/9, 70% overall yield). However, the reaction of 1b with aliphatic alkyne 2g afforded only the branched product 5c in 77% yield without detection of a linear product. In addition to the 1,3-diketones, β-keto esters were also suitable substrates to furnish the branched products 5d,e in 93% and 98% yields, respectively, albeit with almost 1/1 diastereoselectivity. Interestingly, when the phenyl-substituted 1,3-diketone 1f was examined under the

a

Reaction conditions: 0.1 mmol of 1a, 0.2 mmol of 2a, 5 mol % of rhodium catalyst, 12 mol % of ligand, and 6 mol % Lewis acid in 1 mL of DCE at 70 °C for 24 h. bDetermined by GC with n-dodecane as internal standard. cAt 40 °C. d1a/2a = 1/1. e1a/2a = 2/1. f Determined by 1H NMR analysis of the crude reaction mixture.

detected in the absence of Lewis acid or RhI precursors (entries 2 and 3, Table 1). Encouraged by these results, further optimization of the reaction conditions was carried out. We tested other RhI precursors such as [Rh(COD)Cl]2, [Rh(NBD)Cl]2, and Rh(COD)2BF4 together with dppf and found that the catalyst derived from [Rh(COD)Cl]2 is the most efficient, affording 3a in 96% GC yield (entry 4, Table 1). Similarly, the screening of ligands revealed DPEphos to be the superior ligand for this transformation, resulting in the desired branched product 3a in an almost quantitative GC yield (entry 7, Table 1). Then, various Lewis acids such as AlCl3, Gd(OTf)3, Bi(OTf)3, Sc(OTf)3, and La(OTf)3 were examined (entries 10−14, Table 1). The reaction gave the desired product 3a in 87% yield (entry 11, Table 1), while other Lewis acids resulted in poor yield and no desired product formation was observed with AlCl3 (entry 10, Table 1). The reaction became sluggish on lowering of the reaction temperature to 40 °C, resulting in a 20% GC yield of 3a. Interestingly, by a change in the 1a/2a ratio of 1/1, both branched and linear product formations were observed with 90/10 3a/4a in 88% overall yield (entry 16, Table 1). When 2 equiv of acetylacetone (1a) was employed, the formation of 4a increased (entry 17, Table 1). With the optimal reaction conditions in hand (entry 7, Table 1), we explored the scope of the coupling reaction with a large number of alkynes 2 (Scheme 2). Alkynes with electron-rich pmethyl and electron-deficient p-ester or -keto phenyl rings worked smoothly to afford the allylic alkylated products 3b−d in 95−99% yields. Aliphatic alkynes, having more than one possible site for β-H elimination during the formation of the B

DOI: 10.1021/acs.organomet.7b00284 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics optimized reaction conditions (conditions A), a mixture of the branched and linear products (1/16 5f/6f) was obtained in 93% overall yield. In order to achieve high regioselectivity of these types of substrates, further optimization reactions were conducted. We found that in the presence of 5 mol % of [Rh(COD)Cl]2, 12 mol % of BINAP, and 6 mol % of Sc(OTf)3 in DCE at 70 °C for 48 h (conditions B, Scheme 3), the

Scheme 5. Control Experiments

Scheme 3. Reaction Substrate Scope: 1,3-Dicarbonyl Compounds

indicated toward a rapid retro-allylic alkylation under reaction conditions B. The formation of crossover product 3a revealed the involvement of an intermolecular allylic substitution.17 However, intramolecular allylic substitution might be faster, as evidenced by the higher yield of 6f (82% yield), in comparison to that of 3a (18% yield). To figure out the effect of the rhodium complex and Lewis acid in the process of retro-allylic alkylation, several experiments were conducted in the absence of rhodium complex or Lewis acid. These experiments revealed that either of them has an effect on the retro-allylic alkylation; however, the combination of a rhodium complex and Lewis acid can trigger a faster retro-allylic alkylation (see Figures S14S17 in the Supporting Information for more details). To get an intuitive understanding of the different regioselectivities between acetylacetone derivatives and dibenzoylmethane derivatives, the experiments were carried out and monitored by 1H NMR (see Figure S4, S6, S8, and S10 in the Supporting Information for more details). With an increase in the amount of acetylacetone 1a, the yield of linear product 4a was increased (Figures S4, S6 and S8). We speculated that the rhodium complex prefers to coordinate with alkyne 2a, thus hindering the subsequent retro-allylic alkylation. The reaction profile for the progress of the reaction of dibenzoylmethane derivative 1k with 2a showed that there was an initial buildup of the branched product (5k) to reach a peak at around 2 h followed by its decrease as the thermodynamically stable linear product (6k) began to form and exist as a major isomer in the reaction mixture (Figure S10). This observation confirmed that 6k was produced from 5k through a retro-allylic alkylation process. Due to the conjugation effect, dibenzoylmethane derivatives might trigger a faster retro-allylic alkylation in comparison to acetylacetone derivatives. On the basis of these observations, a catalytic cycle was proposed as depicted in Scheme 6. Lewis acid activated substrate 1 would undergo oxidative addition of C−H to the Rh(I) center, resulting in intermediate A (step I). Then, Markovnikov-selective hydrometalation delivers the σ-vinylrhodium intermediate B (step II), which may undergo βhydride elimination to generate an allene and intermediate A′ (step III). A subsequent Markovnikov-selective hydrometalation of this allene would afford the σ-allylrhodium intermediate

reaction of 1 equiv of 1f with 1 equiv of 1a could afford the linear product 6f in 90% yield, exclusively. Under reaction conditions B, various substrates containing either electronwithdrawing (F, Cl, Br) or electron-donating (Me, OMe) groups on the phenyl rings afforded the linear products 6g−k in 63−90% yields. Likewise, 2-naphthyl-substituted 1,3diketone 1l was also amenable to alkylation with 2a to afford 6l in 80% yield. To evaluate the practicality of this catalytic process, a gramscale reaction was carried out. As shown in Scheme 4, the branched allylic alkylation product 3a could be obtained in 92% yield under reaction conditions A. Scheme 4. Gram-Scale Reaction

To gain mechanistic insights into the reaction, the following control experiments were performed (Scheme 5). First, the reaction of 1a with 1-phenylallene 7 under the optimal reaction conditions was performed, affording the corresponding product 3a in 91% yield (eq a, Scheme 5). This experiment demonstrated the formation of an allene intermediate from the alkyne during the course of the reaction. A labeling experiment was also performed with the deuterated 1-phenyl-1propyne 2a-d3 and 1a under the optimal reaction conditions. The deuterium incorporation was observed at the α, β, and γ positions of the carbonyl group (eq b, Scheme 5). Next, the reaction of 1a with mixture of branched/linear products (5f/6f 73/27) was conducted under conditions B (eq c, Scheme 5). After 48 h, the reaction afforded 6f in 82% yield and 3a in 18% yield with full conversion of 5f. This crossover experiment C

DOI: 10.1021/acs.organomet.7b00284 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics

data were obtained on a Bruker Impact II UHR-TOF system. Melting points were measured on an SGW X-4 apparatus. General Procedured for the Addition of 1,3-Dicarbonyl Compound to Internal Alkynes. General Procedure A. In a 10 mL flame-dried Schlenk tube fitted with a rubber septum and magnetic bar, [Rh(COD)Cl]2 (2.5 mg, 0.005 mmol or 5.0 mg, 0.01 mmol), DPEphos (6.5 mg, 0.012 mmol or 13.0 mg, 0.024 mmol), Yb(OTf)3 (3.8 mg, 0.006 mmol or 7.6 mg, 0.012 mmol) were added in the glovebox and then 1,3-dicarbonyl 1a (0.1 or 0.2 mmol) and internal alkyne 2a (0.2 or 0.4 mmol) were added by syringe with 1 or 2 mL of anhydrous dichloroethane (DCE). The tube was sealed and heated to 70 °C for 24−48 h. After the reaction was complete (monitored by TLC), the reaction mixture was directly purified by flash chromatography on silica gel. General Procedure B. In a 10 mL flame-dried Schlenk tube fitted with a rubber septum and magnetic bar, [Rh(COD)Cl]2 (2.5 mg, 0.005 mmol or 5.0 mg, 0.01 mmol), BINAP (7.5 mg, 0.012 mmol or 15.0 mg, 0.024 mmol), and Sc(OTf)3 (3.0 mg, 0.006 mmol or 6.0 mg, 0.012 mmol) were added in the glovebox and then 1,3-dicarbonyl 1a (0.1 or 0.2 mmol) and internal alkyne 2a (0.1 or 0.2 mmol) were added by syringe with 1 or 2 mL of anhydrous dichloroethane (DCE). The tube was sealed and heated to 70 °C for 48−72 h. After the reaction was complete (monitored by TLC), the reaction mixture was directly purified by flash chromatography on silica gel. 3-(1-Phenylallyl)pentane-2,4-dione (3a). This compound was prepared according to the general procedure A to provide 3a as a colorless oil (42.8 mg, 99% yield) after purification by silica gel column chromatography, with 2−5% EtOAc in PE as eluent (elution gradient). The analytical data of 3a were in agreement with those reported.10b 1H NMR (400 MHz, CDCl3): δ 7.32−7.27 (m, 2H), 7.23−7.17 (m, 3H), 5.91−5.82 (m, 1H), 5.10−5.05 (m, 2H), 4.26 (d, J = 11.7 Hz, 1H), 4.19 (dd, J = 11.7, 7.7 Hz, 1H), 2.25 (s, 3H), 1.88 (s, 3H). 3-(1-(p-Tolyl)allyl)pentane-2,4-dione (3b). This compound was prepared according to the general procedure A to provide 3b as a yellow oil (45.5 mg, 99% yield) after purification by silica gel column chromatography, with 5−7% EtOAc in PE as eluent (elution gradient). 1 H NMR (400 MHz, CDCl3): δ 7.11−7.05 (m, 4H), 5.85 (ddd, J = 17.3, 10.2, 7.7 Hz, 1H), 5.08 (m, 2H), 4.24 (d, J = 11.7 Hz, 1H), 4.13 (dd, J = 11.7, 7.8 Hz, 1H), 2.29 (s, 3H), 2.24 (s, 3H), 1.89 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 202.9, 202.8, 138.2, 136.8, 136.7, 129.5, 127.7, 116.1, 74.2, 49.4, 29.9, 29.5, 20.9. IR (KBr): 525, 819, 923, 1154, 1356, 1513, 1699, 2364, 2924, 3005. HRMS (ESI+): calcd for [C15H18O2 + Na]+, 253.1199; found, 253.1201. Ethyl 4-(4-Acetyl-5-oxohex-1-en-3-yl)benzoate (3c). This compound was prepared according to the general procedure A to provide 3c as a yellow oil (57.0 mg, 99% yield) after purification by silica gel column chromatography, with 5−7% EtOAc in PE as eluent (elution gradient). 1H NMR (400 MHz, CDCl3): δ 7.99 (d, J = 8.4 Hz, 2H), 7.29 (d, J = 8.3 Hz, 2H), 5.90−5.81 (m, 1H), 5.12 (dd, J = 13.8, 3.3 Hz, 2H), 4.36 (q, J = 7.1 Hz, 2H), 4.32−4.23 (m, 2H), 2.25 (s, 3H), 1.91 (s, 3H), 1.39 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 202.2, 202.0, 166.1, 149.9, 137.1, 130.0, 129.4, 127.9, 117.1, 73.9, 60.8, 49.4, 29.9, 29.4, 14.2. IR (KBr): 768, 857, 927, 1020, 1106, 1182, 1278, 1359, 1609, 1716, 2366, 2982. HRMS (ESI+): calcd for [C17H20O4 + Na]+, 311.1254; found, 311.1255. 3-(1-(4-Pentanoylphenyl)allyl)pentane-2,4-dione (3d). This compound was prepared according to the general procedure A to provide 3d as a yellow oil (57.1 mg, 95% yield) after purification by silica gel column chromatography, with 5−7% EtOAc in PE as eluent (elution gradient). 1H NMR (400 MHz, CDCl3): δ 7.91 (d, J = 8.4 Hz, 2H), 7.30 (d, J = 8.4 Hz, 2H), 5.89−5.81 (m, 1H), 5.12−5.08 (m, 2H), 4.31−4.23 (m, 2H), 2.94 (t, J = 7.4 Hz, 2H), 2.25 (s, 3H), 1.92 (s, 3H), 1.74 (p, J = 7.6 Hz, 2H), 1.45 (td, J = 15.0, 7.5 Hz, 2H), 0.96 (t, J = 7.4 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 202.2, 202.1, 199.9, 145.1, 137.1, 136.0, 128.6, 128.1, 117.3, 73.9, 49.4, 38.23, 30.0, 29.4, 26.4, 22.4, 13.8. IR (KBr): 926, 1010, 1183, 1267, 1358, 1605, 1699, 2366, 2958. HRMS (ESI+): calcd for [C19H24O3 + Na]+, 323.1618; found, 323.1617. 3-(5-Phenylpent-1-en-3-yl)pentane-2,4-dione (3e). This compound was prepared according to the general procedure A to provide

Scheme 6. Proposed Catalytic Cycle

C (step IV), which may be attacked by 1 to furnish the desired branched product 3.

■

CONCLUSIONS In conclusion, we have developed an efficient approach toward the regioselective addition of 1,3-dicarbonyl compounds to internal alkynes to produce allylic alkylated products. The branched and linear allylic products were selectively obtained in good to excellent yields by employing 1,3-dicarbonyl compounds with different substituents. The branched allylic alkylated products were obtained from 1,3-dicarbonyl compounds with aliphatic substituents, whereas linear allylic alkylated products were achieved from those aromatic substituents. Furthermore, a retro-allylic alkylation process was observed in this protocol. The use of a catalytic amount of Lewis acid in combination with the rhodium(I) complex was crucial for success in achieving this transformation. Assisted by a Lewis acid, direct C−H oxidative addition toward the rhodium(I) complex might be involved in this transformation. By alteriation of the reaction conditions, branched and linear allylic products were selectively obtained. Further exploration of the rhodium(I)/Lewis acid catalytic system is currently underway in our laboratory.

■

EXPERIMENTAL SECTION

All nonaqueous reactions were performed in oven-dried glassware and standard Schlenk tubes under an atmosphere of nitrogen. 1,2Dichloroethane (DCE), 1,2-dichlorobenzene (ODCB), and acetonitrile (CH3CN) were distilled from CaH2 under an inert atmosphere. Tetrahydrofuran (THF), dioxane, and toluene (PhMe) were distilled from sodium and benzophenone under an inert atmosphere. All other solvents and reagents were used as received unless otherwise noted. Thin-layer chromatography was performed using silica gel 60 F-254 precoated plates (0.2−0.3 mm) and visualized by short-wave UV (254 nm) irradiation, potassium permanganate, CAM, or iodine stain. The 1 H and 13C NMR spectra were obtained in CDCl3 using a Bruker Avance III spectrometer at 400 and 100 MHz for 1H and 13C NMR, respectively. Chemical shifts (δ) for 1H NMR spectra are recorded in parts per million from tetramethylsilane with the solvent resonance as the internal standard (chloroform, δ 7.26 ppm). Data are reported as follows: chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, qn = quintet, m = multiplet, and br = broad), coupling constant in Hz, and integration. Chemical shifts for 13C NMR spectra are recorded in parts per million from tetramethylsilane using the central peak of deuteriochloroform (δ 77.00 ppm) as the internal standard. The infrared spectra were recorded on a VERTEX 70 IR spectrometer as KBr pellets, with absorption reported in cm−1. HRMS D

DOI: 10.1021/acs.organomet.7b00284 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics

C NMR (100 MHz, CDCl3): δ 203.0, 202.9, 144.7, 136.9, 132.9, 129.8, 127.8, 118.5, 74.2, 69.9, 43.6, 30.2, 29.4, 28.1, 26.3, 21.5. IR (KBr): 555, 664, 816, 927, 1176, 1358, 1699, 2366, 2926. HRMS (ESI+): calcd for [C18H24O5S + Na]+, 375.1237; found, 375.1237. 3-(6-Hydroxyhex-1-en-3-yl)pentane-2,4-dione (3k). This compound was prepared according to the general procedure A to provide 3k as a colorless oil (22.6 mg, 57% yield) after purification by silica gel column chromatography, with 33−35% EtOAc in PE as eluent (elution gradient). 1H NMR (400 MHz, CDCl3): δ 5.53−5.43 (m, 1H), 5.12−5.08 (m, 2H), 3.70 (d, J = 10.4 Hz, 1H), 3.64 (t, J = 6.0 Hz, 2H), 2.93 (qd, J = 10.3, 2.8 Hz, 1H), 2.21 (s, 3H), 2.11 (s, 3H), 1.72 (s, 1H), 1.65−1.58 (m, 1H), 1.51−1.38 (m, 2H), 1.24−1.18 (m, 1H). 13 C NMR (100 MHz, CDCl3): δ 203.7, 203.4, 137.5, 118.1, 74.6, 62.2, 43.8, 30.3, 29.7, 29.4, 28.6. IR (KBr): 923, 1153, 1359, 1419, 1541, 1697, 2363, 2934. HRMS (ESI+): calcd for [C11H18O3 + Na]+, 221.1154; found, 221.1149. 3-(6-Chlorohex-1-en-3-yl)pentane-2,4-dione (3l). This compound was prepared according to the general procedure A to provide 3l as a yellow oil (42.2 mg, 97% yield) after purification by silica gel column chromatography, with 5−7% EtOAc in PE as eluent (elution gradient). 1 H NMR (400 MHz, CDCl3): δ 5.53−5.42 (m, 1H), 5.13−5.09 (m, 2H), 3.70 (d, J = 10.5 Hz, 1H), 3.56−3.45 (m, 2H), 2. 93 (qd, J = 10.4, 3.1 Hz, 1H), 2.21 (s, 3H), 2.11 (s, 3H), 1.84−1.76 (m, 1H), 1.73−1.66 (m, 1H), 1.52−1.44 (m, 1H), 1.30−1.25 (m, 1H). 13C NMR (100 MHz, CDCl3): δ 203.3, 203.1, 137.2, 118.3, 74.5, 44.5, 43.6, 30.0, 29.8, 29.5. IR (KBr): 925, 1147, 1358, 1420, 1699, 2367, 2929. HRMS (ESI+): calcd for [C11H17O2Cl + Na]+, 239.0809; found, 239.0810. 5-Acetyl-2,2-dimethyl-1-phenyl-4-vinylheptane-1,6-dione (3m). This compound was prepared according to the general procedure A to provide 3m as a colorless oil (28.3 mg, 47% yield) after purification by silica gel column chromatography, with 5−7% EtOAc in PE as eluent (elution gradient). 1H NMR (400 MHz, CDCl3): δ 7.60−7.58 (m, 2H), 7.47−7.43(m, 1H), 7.38 (t, J = 7.6 Hz, 2H), 5.40−5.30 (m, 1H), 5.02−4.92 (m, 2H), 3.69 (d, J = 10.0 Hz, 1H), 3.10 (qd, J = 10.4, 2.7 Hz, 1H), 2.19 (s, 3H), 2.16 (dd, J = 12.0, 3.0 Hz, 1H), 2.06 (s, 3H), 1.51 (dd, J = 13.8, 2.6 Hz, 1H) 1.34 (d, J = 2.7 Hz, 6H). 13C NMR (100 MHz, CDCl3): δ 208.6, 203.4, 203.2, 138.9, 138.2, 130.8, 128.0, 127.9, 118.2, 74.8, 47.0, 42.6, 42.1, 30.2, 29.9, 28.9, 25.4. IR (KBr): 1361, 1419, 1473, 1558, 1698, 1733, 2365.98, 2971. HRMS (ESI+): calcd for [C19H24O3 + Na]+, 323.1618; found, 323.1621. N-(3-Acetyl-4-oxo-2-vinylpentyl)-N-benzyl-4-methylbenzenesulfonamide (3n). This compound was prepared according to the general procedure A to provide 3n as a colorless oil (50.4 mg, 61% yield) after purification by silica gel column chromatography, with 9−12% EtOAc in PE as eluent (elution gradient). 1H NMR (400 MHz, CDCl3): δ 7.67 (d, J = 8.6 Hz, 2H), 7.33−7.28 (m, 7H), 5.68 (dt, J = 17.2, 9.9 Hz, 1H), 4.95 (dd, J = 10.2, 1.2 Hz, 1H), 4.76 (d, J = 17.2 Hz, 1H), 4.50 (d, J = 14.6 Hz, 1H), 4.10 (d, J = 14.6 Hz, 1H), 3.86 (d, J = 7.0 Hz, 1H), 3.31 (dd, J = 14.2, 7.7 Hz, 1H), 2.94 (dd, J = 14.2, 6.8 Hz, 1H), 2.72 (m, 1H), 2.44 (s, 3H), 2.06 (s, 3H), 1.94 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 203.9, 203.5, 143.5, 136.2, 136.0, 135.3, 129.7, 128.9, 128.6, 128.1, 127.2, 118.9, 68.6, 54.0, 51.7, 43.3, 30.2, 29.4, 21.4. IR (KBr): 549, 656, 699, 928, 1159, 1339, 1496, 1699, 2364, 2925. HRMS (ESI+): calcd for [C23H27NO4S + H]+, 414.1734; found, 414.1731. N-(5-Acetyl-6-oxo-4-vinylheptyl)-2,2,2-trifluoroacetamide (3o). This compound was prepared according to the general procedure A to provide 3o as a colorless oil (45.2 mg, 77% yield) after purification by silica gel column chromatography, with 17−20% EtOAc in PE as eluent (elution gradient). 1H NMR (400 MHz, CDCl3): δ 6.72 (s, 1H), 5.52−5.42 (m, 1H), 5.15−5.08 (m, 2H), 3.71 (d, J = 10.8 Hz, 1H), 3.47 (td, J = 13.4, 6.3 Hz, 1H), 3.36 (td, J = 12.4, 5.5 Hz,1H), 2.90 (qd, J = 10.4, 2.9 Hz, 1H), 2.20 (s, 3H), 2.11 (s, 3H), 1.68−1.59 (m, 1H), 1.57−1.45 (m, 1H), 1.39−1.32 (m, 1H), 1.26−1.15 (m, 1H). 13 C NMR (100 MHz, CDCl3): δ 203.6, 203.0, 157.2 (q, J = 36.6 Hz), 137.0, 118.6, 115.8 (q, J = 286.3 Hz), 74.1, 43.0, 39.1, 30.5, 29.4, 29.1, 25.8. 19F NMR (376 MHz, CDCl3): δ −75.93. IR (KBr): 1156, 1361, 1419, 1457, 1508, 1699, 2365, 2940. HRMS (ESI+): calcd for [C13H18NO3F3 + Na]+, 316.1131; found, 316.1133. 13

3e as a colorless oil (30.7 mg, 63% yield) after purification by silica gel column chromatography, with 9−12% DCM in PE as eluent (elution gradient). 1H NMR (400 MHz, CDCl3): δ 7.29−7.25 (m, 2H), 7.18 (d, J = 7.2 Hz, 1H), 7.14 (d, J = 7.2 Hz, 2H), 5.60−5.50 (m, 1H), 5.19−5.12 (m, 2H), 3.70 (d, J = 10.4 Hz, 1H), 2.91 (qd, J = 10.4, 3.0 Hz, 1H), 2.73−2.64 (m, 1H), 2.52−2.44 (m, 1H), 2.11 (s, 3H), 2.09 (s, 3H), 1.67−1.58 (m, 1H), 1.53−1.44 (m, 1H). 13C NMR (100 MHz, CDCl3): δ 203.5, 203.3, 141.5, 137.5, 128.4, 128.3, 125.9, 118.4, 74.6, 43.9, 34.2, 33.0, 29.9, 29.6. IR (KBr): 700, 47, 923, 1149, 1357, 1455, 1698, 2367, 2928. HRMS (ESI+): calcd for [C16H20O2 + Na]+, 267.1356; found, 267.1357. 3-(Non-1-en-3-yl)pentane-2,4-dione (3f). This compound was prepared according to the general procedure A to provide 3f as a colorless oil (18.4 mg, 82% yield) after purification by silica gel column chromatography, with 33−35% DCM in PE as eluent (elution gradient). 1H NMR (400 MHz, CDCl3): δ 5.51−5.42 (m, 1H), 5.09− 5.05 (m, 2H), 3.68 (d, J = 10.6 Hz, 1H), 2.86 (dd, J = 19.4, 9.6 Hz, 1H), 2.20 (s, 3H), 2.10 (s, 3H), 1.28−1.18 (m, 10H), 0.87 (t, J = 6.4 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 203.7, 203.6, 137.9, 117.6, 74.8, 44.8, 32.5, 31.6, 30.2, 29.5, 28.9, 26.7, 22.5, 14.0. IR (KBr): 1360, 1457, 1541, 1558, 1699, 2364, 2857, 2928. HRMS (ESI+): calcd for [C14H24O2 + Na]+, 247.1669; found, 247.1670. 3-(6-(Benzyloxy)hex-1-en-3-yl)pentane-2,4-dione (3g). This compound was prepared according to the general procedure A to provide 3g as a colorless oil (55.1 mg, 95% yield) after purification by silica gel column chromatography, with 5−7% EtOAc in PE as eluent (elution gradient). 1H NMR (400 MHz, CDCl3): δ 7.36−7.26 (m, 5H), 5.51− 5.42 (m, 1H), 5.09−5.05 (m, 2H), 4.47 (s, 2H), 3.69 (t, J = 10.6 Hz, 1H), 3.47−3.38 (m, 2H), 2.92 (qd, J = 10.4, 3.4 Hz, 1H), 2.18 (s, 3H), 2.09 (s, 3H), 1.72−1.61 (m, 1H), 1.54−1.48 (m, 1H), 1.43−1.37 (m, 1H), 1.29−1.22 (m, 1H). 13C NMR (100 MHz, CDCl3): δ 203.5, 203.4, 138.4, 137.6, 128.3, 127.5, 127.5 117.9, 74.6, 72.8, 69.7, 44.1, 30.1, 29.5, 28.9, 26.9. IR (KBr): 698, 739, 923, 1102, 1274, 1358, 1698, 2365, 2858, 2930. HRMS (ESI+): calcd for [C18H24O3 + Na]+, 311.1618; found, 311.1620. 5-Acetyl-6-oxo-4-vinylheptyl Benzoate (3h). This compound was prepared according to the general procedure A to provide 3h as a colorless oil (54.4 mg, 90% yield) after purification by silica gel column chromatography, with 5−7% EtOAc in PE as eluent (elution gradient). 1 H NMR (400 MHz, CDCl3): δ 8.03−8.00 (m, 2H), 7.58−7.54 (m, 1H), 7.46 (t, J = 7.6 Hz, 2H), 5.55−5.46 (m, 1H), 5.15−5.11 (m, 2H), 4.32−4.24 (m, 2H), 3.72 (t, J = 10.4 Hz, 1H), 2.98 (qd, J = 10.3, 3.1 Hz, 1H), 2.19 (s, 3H), 2.11 (s, 3H), 1.88−1.78 (m, 1H), 1.73−1.62 (m, 1H), 1.54−1.45 (m, 1H), 1.31−1.25 (m, 1H). 13C NMR (100 MHz, CDCl3): δ 203.3, 203.2, 166.5, 137.3, 132.9, 130.2, 129.5, 128.3, 118.3, 74.5, 64.4, 43.9, 30.1, 29.4, 28.8, 26.1. IR (KBr): 714, 925, 1070, 1116, 1275, 1358, 1452, 1717, 2368, 2929. HRMS (ESI+): calcd for [C18H22O4 + Na]+, 325.1410; found, 325.1411. 3-(6-((tert-Butyldimethylsilyl)oxy)hex-1-en-3-yl)pentane-2,4dione (3i). This compound was prepared according to the general procedure A to provide 3i as a colorless oil (47.4 mg, 76% yield) after purification by silica gel column chromatography, with 2−5% EtOAc in PE as eluent (elution gradient). 1H NMR (400 MHz, CDCl3): δ 5.47 (ddd, J = 18.3, 13.5, 9.4 Hz, 1H), 5.07−5.03 (m, 2H), 3.66 (d, J = 10.6 Hz, 1H), 3.55 (t, J = 6.0 Hz, 2H), 2.89 (qd, J = 10.4, 2.7 Hz, 1H), 2.16 (s, 3H), 2.07 (s, 3H), 1.55−1.48 (m, 1H), 1.42−1.32 (m, 2H), 1.23−1.15 (m, 1H), 0.85 (s, 9H), 0.03 (s, 6H). 13C NMR (100 MHz, CDCl3): δ 203.6, 203.5, 137.8, 117.8, 74.7, 62.6, 44.2, 30.0, 29.9, 29.6, 28.7, 25.9, 18.2, −5.3. IR (KBr): 775, 835, 1099, 1255, 1358, 1472, 1700, 2366, 2857, 2930. HRMS (ESI+): calcd for [C17H32O3Si + Na]+, 335.2013; found, 335.2014. 5-Acetyl-6-oxo-4-vinylheptyl 4-Methylbenzenesulfonate (3j). This compound was prepared according to the general procedure A to provide 3j as a colorless oil (56.3 mg, 80% yield) after purification by silica gel column chromatography, with 17−20% EtOAc in PE as eluent (elution gradient). 1H NMR (400 MHz, CDCl3): δ 7.77 (d, J = 8.2 Hz, 2H), 7.35 (d, J = 8.0 Hz, 2H), 5.46−5.36 (m, 1H), 5.09−5.02 (m, 2H), 4.00−3.96 (m, 2H), 3.65 (d, J = 10.4 Hz, 1H), 2.84 (qd, J = 10.3, 2.9 Hz, 1H), 2.45 (s, 3H), 2.17 (s, 3H), 2.08 (s, 3H), 1.73−1.67 (m, 1H), 1.57−1.49 (m, 1H), 1.38−1.30 (m, 1H), 1.23−1.16 (m, 1H). E

DOI: 10.1021/acs.organomet.7b00284 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics 3-(5-(((8R,9S,13S,14S)-13-Methyl-17-oxo7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-3-yl)oxy)pent-1-en-3-yl)pentane-2,4-dione (3q). This compound was prepared according to the general procedure A to provide 3q as a yellow oil (76.1 mg, 87% yield) after purification by silica gel column chromatography, with 9−12% EtOAc in PE as eluent (elution gradient). 1H NMR (400 MHz, CDCl3): δ 7.19 (d, J = 8.6 Hz, 1H), 6.69 (dd, J = 8.6, 2.6 Hz, 1H), 6.61 (d, J = 2.5 Hz, 1H), 5.63− 5.52 (m, 1H), 5.14−5.10 (m, 2H), 3.97−3.83 (m, 2H), 3.81 (d, J = 10.4 Hz, 1H), 3.22 (qd, J = 10.0, 3.3 Hz, 1H), 2.90−2.87 (m, 2H), 2.53 (dd, J = 18.7, 8.6 Hz, 1H), 2.41−2.37 (m, 1H), 2.23 (s, 3H), 2.20−2.15 (m, 1H), 2.13 (s, 3H), 2.12−1.93 (m, 4H), 1.87−1.79 (m, 1H), 1.69−1.52 (m, 4H), 1.47−1.38 (m, 2H), 1.25 (s, 1H), 0.91 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 220.9, 203.4, 203.4, 156.6, 137.7, 136.9, 132.1, 126.2, 118.5, 114.4, 112.0, 73.9, 64.7, 50.3, 47.9, 43.9, 41.0, 38.3, 35.8, 31.8, 31.5, 29.8, 29.7, 29.6, 26.5, 25.8, 21.5, 13.8. IR (KBr): 1055, 1159, 1253, 1358, 1499, 1698, 1737, 2366, 2928. HRMS (ESI+): calcd for [C28H36O4 + Na]+, 459.2506; found, 459.2504. (E)-3-(1-Phenylbut-2-en-1-yl)pentane-2,4-dione (3r). This compound was prepared according to the general procedure A to provide 3r as a colorless oil (39.6 mg, 43% yield) after purification by silica gel column chromatography, with 1−3% EtOAc in PE as eluent (elution gradient). 1H NMR (400 MHz, CDCl3): δ 7.29 (t, J = 7.3 Hz, 2H), 7.19 (t, J = 9.6 Hz, 3H), 5.55−5.44 (m, 2H), 4.23 (d, J = 11.7 Hz, 1H), 4.12(dd, J = 11.6, 7.1 Hz, 1H), 2.23 (s, 3H), 1.87 (s, 3H), 1.61 (d, J = 5.2 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 203.0, 202.9, 140.73, 130.7, 128.8, 127.7, 127.4, 126.9, 74.6, 49.1, 30.0, 29.5, 17.8. IR (KBr): 700, 755, 967, 1153, 1356, 1453, 1699, 2363, 2919, 3029. HRMS (ESI+): calcd for [C15H18O2 + Na]+, 253.1199; found, 253.1200. (E)-3-(4-Phenylbut-3-en-2-yl)pentane-2,4-dione (3r′). This compound was prepared according to the general procedure A to provide 3r′ as a colorless oil (41.4 mg, 45% yield) after purification by silica gel column chromatography, with 1−3% EtOAc in PE as eluent (elution gradient). 1H NMR (400 MHz, CDCl3): δ 7.33−7.26 (m, 4H), 7.24− 7.19 (m, 1H), 6.44 (d, J = 15.9 Hz, 1H), 5.99 (dd, J = 15.9, 8.5 Hz, 1H), 3.70 (d, J = 10.3 Hz, 1H), 3.27−3.15 (m, 1H), 2.22 (s, 3H), 2.13 (s, 3H), 1.08 (d, J = 6.7 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 203.5, 203.4, 136.7, 130.9, 130.9, 128.5, 127.5, 126.2, 75.5, 37.8, 29.9, 29.6, 18.8. IR (KBr): 694, 749, 969, 1155, 1357, 1492, 1698, 2362, 2926, 2966, 3026. HRMS (ESI+): calcd for [C15H18O2 + Na]+, 253.1199; found, 253.1201. 4-(1-Phenylallyl)heptane-3,5-dione (5a). This compound was prepared according to the general procedure A to provide 5a as a colorless oil (24.1 mg, 99% yield) after purification by silica gel column chromatography, with 17−20% DCM in PE as eluent (elution gradient). 1H NMR (400 MHz, CDCl3) of 5a: δ 7.28 (d, J = 7.4 Hz, 2H), 7.22−7.16 (m, 3H), 5.86 (ddd, J = 17.1, 10.5, 7.2 Hz, 1H), 5.07− 5.03 (m, 2H), 4.27−4.18 (m, 2H), 2.61 (qd, J = 7.5, 1.9 Hz, 2H), 2.26 (dq, J = 18.4, 7.4 Hz, 1H), 2.08 (dq, J = 18.4, 7.2 Hz, 1H), 1.03 (t, J = 7.1 Hz, 3H), 0.72 (t, J = 7.2 Hz, 3H). 1H NMR (400 MHz, CDCl3) of 6a: δ 7.30 (m, 5H), 6.45 (d, J = 15.6 Hz, 1H), 6.09−6.01 (m, 1H), 3.84 (t, J = 7.0 Hz, 1H), 2.76 (m, 2H), 2.53−2.42 (m, 4H), 1.05 (t, J = 6.8 Hz, 6H). 13C NMR (100 MHz, CDCl3) of 5a: δ 205.3, 140.1, 138.2, 128.8, 127.9, 127.1, 116.4, 72.9, 49.8, 36.3, 35.6, 7.3, 7.1. IR (KBr): 702, 922, 1101, 1347, 1456, 1699, 1733, 2939, 2979. HRMS (ESI+): calcd for [C16H20O2 + Na]+, 267.1356; found, 267.1359. 2,6-Dimethyl-4-(1-phenylallyl)heptane-3,5-dione (5b). This compound was prepared according to the general procedure A to provide 5b as a colorless oil (19.1 mg, 70% yield) after purification by silica gel column chromatography, with 17−20% DCM in PE as eluent (elution gradient). 1H NMR (400 MHz, CDCl3) of 5b: δ 7.29 (m, 2H), 7.20 (m, 3H), 5.89 (ddd, J = 17.2, 10.2, 8.2 Hz, 1H), 5.08 (m, 2H), 4.46 (d, J = 11.8 Hz, 1H), 4.29 (dd, J = 11.2, 8.2 Hz, 1H), 2.90−2.83 (m, 1H), 2.51−2.42 (m, 1H), 1.09 (dd, J = 15.8, 6.8 Hz, 6H), 0.73 (d, J = 6.8 Hz, 3H), 0.63 (d, J = 6.9 Hz, 3H). 1H NMR (400 MHz, CDCl3) of 6b: δ 7.29 (m, 5H), 6.45 (d, J = 15.8 Hz, 1H), 6.09 (m, 1H), 4.11 (t, J = 7.0 Hz, 1H), 2.79−2.71 (m, 4H), 1.12 (dd, J = 15.6, 6.8 Hz, 12H). 13C NMR (100 MHz, CDCl3) of 5b: δ 208.4, 208.3, 140.4, 138.4, 128.7, 128.3, 127.0, 116.7, 71.5, 50.2, 40.6, 40.3, 18.8, 18.2, 18.1, 17.7. IR

(KBr): 701, 758, 921, 1058, 1465, 1696, 1728, 2934, 2973. HRMS (ESI+): calcd for [C18H24O2 + Na]+, 295.1669; found, 295.1667. 4-(6-(Benzyloxy)hex-1-en-3-yl)heptane-3,5-dione (5c). This compound was prepared according to the general procedure A to provide 5c as a colorless oil (49.6 mg, 77% yield) after purification by silica gel column chromatography, with 5−7% EtOAc in PE as eluent (elution gradient). 1H NMR (400 MHz, CDCl3): δ 7.36−7.29 (m, 4H), 7.29− 7.25 (m, 1H), 5.49−5.40 (m, 1H), 5.09−5.01 (m, 2H), 4.47 (s, 2H), 3.70 (d, J = 10.9 Hz, 1H), 3.49−3.37 (m, 2H), 2.95 (qd, J = 10.4, 3.1 Hz, 1H), 2.51−2.38 (m, 4H), 1.70−1.61 (m, 1H), 1.54−1.44 (m, 1H), 1.41−1.33 (m, 1H), 1.24−1.19 (m, 1H), 1.01 (t, J = 7.4 Hz, 3H), 0.97 (t, J = 7.4 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 206.0, 205.9, 138.4, 137.8, 128.2, 127.5, 127.4, 117.7, 73.1, 72.8, 69.7, 44.3, 36.1, 35.7, 29.0, 26.9, 7.4, 7.2. IR (KBr): 698, 737, 921, 1102, 1352, 1456, 1698, 2857, 2938. HRMS (ESI+): calcd for [C20H28O3 + Na]+, 339.1931; found, 339.1930. Methyl 2-Acetyl-3-phenylpent-4-enoate (5d). This compound was prepared according to the general procedure A to provide 5d as a colorless oil (21.6 mg, 93% yield) after purification by silica gel column chromatography, with 33−35% DCM in PE as eluent (elution gradient). Major diastereomer: 1H NMR (400 MHz, CDCl3): δ 7.31− 7.28 (m, 2H), 7.23−7.19 (m, 3H), 6.00−5.86 (m, 1H), 5.12−5.05 (m, 2H), 4.15−4.10 (m, 1H), 4.05−3.98 (m, 1H), 3.73 (s, 3H), 1.98 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 201.4, 168.4, 139.8, 138.1, 128.8, 127.9, 127.2, 116.3, 64.8, 52.5, 49.5, 29.7. Minor diastereomer: 1 H NMR (400 MHz, CDCl3): δ 7.31−7.28 (m, 2H), 7.23−7.19 (m, 3H), 6.00−5.86 (m, 1H), 5.12−5.05 (m, 2H), 4.15−4.10 (m, 1H), 4.05−3.98 (m, 1H), 3.46 (s, 3H), 2.29 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 201.6, 168.1, 140.1, 137.8, 128.6, 127.8, 127.1, 116.7, 65.2, 52.3, 49.4, 30.1. IR (KBr): 700, 1157, 1419, 1490, 1541, 1717, 2367, 2953. HRMS (ESI+): calcd for [C14H16O3 + Na]+, 255.0992; found, 255.0992. 3-Acetyl-3-(1-phenylallyl)dihydrofuran-2(3H)-one (5e). This compound was prepared according to the general procedure A to provide 5e as a colorless oil (24.2 mg, 98% yield) after purification by silica gel column chromatography, with 33−35% DCM in PE as eluent (elution gradient). Data for the major diastereomer are as follows. 1H NMR (400 MHz, CDCl3): δ 7.32−7.26 (m, 3H), 7.15 (d, J = 7.6 Hz, 2H), 6.05−5.91 (m, 1H), 5.28−5.19 (m, 1H), 5.02 (dd, J = 16.9, 0.6 Hz, 1H), 4.42 (d, J = 7.0 Hz, 1H), 4.17−4.07 (m, 2H), 3. 07−2.99 (m, 1H), 2.56−2.49 (m, 1H), 2.22 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 201.1, 174.7, 137.9, 136.1, 128.9, 128.5, 127.6, 119.4, 66.2, 53.0, 26.5, 24.3. Data for the minor diastereomer are as follows. 1H NMR (400 MHz, CDCl3): δ 7.32−7.26 (m, 5H), 6.05−5.91 (m, 1H), 5.28−5.19 (m, 2H), 4.49 (d, J = 8.8 Hz, 1H), 4.00 (q, J = 8.0 Hz, 1H), 3.54 (td, J = 8.6, 4.8 Hz, 0.1H), 3.07−2.99 (m, 1H), 2.45 (s, 3H), 2.24−2.16 (m, 1H). 13C NMR (100 MHz, CDCl3): δ 201.4, 174.4, 137.5, 134.7, 129.1, 128.7, 127.7, 119.0, 66.4, 51.8, 26.2, 25.7. IR (KBr): 703, 931, 1028, 1162, 1375, 1491, 1712, 1760, 2363, 2920. HRMS (ESI+): calcd for [C15H16O3 + Na]+, 267.0997; found, 267.0992. 2-Cinnamyl-1,3-diphenylpropane-1,3-dione (6f). This compound was prepared according to the general procedure B to provide 6f as a colorless oil (29.2 mg, 90% yield) after purification by silica gel column chromatography, with 2−5% EtOAc in PE as eluent (elution gradient). 1 H NMR (400 MHz, CDCl3): δ 7.98 (d, J = 7.8 Hz, 4H), 7.58 (t, J = 7.2 Hz, 2H), 7.47 (t, J = 7.2 Hz, 4H), 7.26 (d, J = 3.6 Hz, 4H), 7.19− 7.18 (m, 1H), 6.48 (d, J = 15.8 Hz, 1H), 6.28−6.20 (m, 1H), 5.37 (t, J = 6.6 Hz, 1H), 3.04 (t, J = 6.9 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 195.5, 136.9, 135.9, 133.5, 132.5, 128.9, 128.6, 128.4, 127.3, 126.7, 126.1, 57.2, 32.9. IR (KBr): 692, 746, 966, 1263, 1448, 1559, 1696, 2345, 2926, 3026, 3059. HRMS (ESI+): calcd for [C24H20O2 + Na]+, 363.1356; found, 363.1357. 2-Cinnamyl-1,3-bis(4-fluorophenyl)propane-1,3-dione (6g). This compound was prepared according to the general procedure B to provide 6g as a colorless oil (23.7 mg, 63% yield) after purification by silica gel column chromatography, with 2−5% EtOAc in PE as eluent (elution gradient). 1H NMR (400 MHz, CDCl3): δ 8.00−7.96 (m, 2H), 7.90 (d, J = 8.6 Hz, 2H), 7.44 (d, J = 8.5 Hz, 2H), 7.26 (d, J = 4.2 Hz, 4H), 7.23−7.17 (m, 1H), 7.15 (t, J = 8.5 Hz, 2H), 6.47 (d, J = 15.8 Hz, 1H), 6.24−6.16 (m, 1H), 5.23 (t, J = 6.7 Hz, 1H), 3.01 (t, J = 6.6 F

DOI: 10.1021/acs.organomet.7b00284 Organometallics XXXX, XXX, XXX−XXX

Organometallics

■

Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 194.2, 193.8, 167.3 (d, J = 255.8 Hz), 140.3, 136.8, 134.2, 132.8, 132.2 (d, J = 2.8 Hz), 131.4 (d, J = 9.4 Hz), 129.9, 129.3, 128.5, 127.5, 126.2, 126.1, 116.3 (d, J = 22.0 Hz), 57.6, 32.9. 19F NMR (376 MHz, CDCl3): δ −103.63 (tt, J = 8.2, 5.3 Hz). IR (KBr): 741, 847, 965, 1156, 1234, 1399, 1507, 1595, 1697, 2364, 2926. HRMS (ESI+): calcd for [C24H18O2F2 + Na]+, 399.1167; found, 399.1161. 1,3-Bis(4-chlorophenyl)-2-cinnamylpropane-1,3-dione (6h). This compound was prepared according to the general procedure B to provide 6h as a colorless oil (30.7 mg, 75% yield) after purification by silica gel column chromatography, with 2−5% EtOAc in PE as eluent (elution gradient). 1H NMR (400 MHz, CDCl3): δ 7.89 (d, J = 8.6 Hz, 4H), 7.42 (d, J = 8.6 Hz, 4H), 7.26−7.25 (m, 4H), 7.23−7.17 (m, 1H), 6.46 (d, J = 15.8 Hz, 1H), 6.23−6.16 (m, 1H), 5.21 (t, J = 6.4 Hz, 1H), 3.00 (t, J = 6.7 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 194.2, 140.3, 136.7, 134.2, 132.8, 129.9, 129.3, 128.5, 127.5, 126.1, 126.1, 57.5, 32.9. IR (KBr): 741, 1093, 1263, 1399, 1588, 1697, 2362, 3026. HRMS (ESI+): calcd for [C24H18O2Cl2 + Na]+, 431.0576; found, 431.0573. 1,3-Bis(4-bromophenyl)-2-cinnamylpropane-1,3-dione (6i). This compound was prepared according to the general procedure B to provide 6i as a colorless oil (32.9 mg, 66% yield) after purification by silica gel column chromatography, with 2−5% EtOAc in PE as eluent (elution gradient). 1H NMR (400 MHz, CDCl3): δ 7.80 (d, J = 8.6 Hz, 4H), 7.60 (d, J = 8.6 Hz, 4H), 7.28−7.25 (m, 4H), 7.22−7.17 (m, 1H), 6.46 (d, J = 15.6 Hz, 1H), 6.23−6.15 (m, 1H), 5.21 (t, J = 6.7 Hz, 1H), 3.00 (t, J = 6.6 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 194.4, 136.7, 134.6, 132.9, 132.3, 130.0, 129.1, 128.5, 127.5, 126.2, 126.0, 57.5, 32.8. IR (KBr): 737, 840, 1008, 1071, 1262, 1396, 1583, 1697, 2363, 3026. HRMS (ESI+): calcd for [C24H18O2Br2 + Na]+, 518.9566; found, 518.9564. 2-Cinnamyl-1,3-di-p-tolylpropane-1,3-dione (6j). This compound was prepared according to the general procedure B to provide 6j as a colorless oil (27.9 mg, 76% yield) after purification by silica gel column chromatography, with 2−5% EtOAc in PE as eluent (elution gradient). 1 H NMR (400 MHz, CDCl3): δ 7.88 (d, J = 8.2 Hz, 4H), 7.26−7.22 (m, 8H), 7.19−7.16 (m, 1H), 6.47 (d, J = 15.8 Hz, 1H), 6.28−6.20 (m, 1H), 5.30 (t, J = 6.8 Hz, 1H), 3.00 (t, J = 6.8 Hz, 2H), 2.38 (s, 6H). 13C NMR (100 MHz, CDCl3): δ 195.2, 144.4, 137.1, 133.5, 132.2, 129.6, 128.7, 128.4, 127.2, 127.0, 126.1, 57.2, 33.0, 21.6. IR (KBr): 741, 818, 964, 1179, 1265, 1559, 1691, 2365, 2920, 3028. HRMS (ESI+): calcd for [C26H24O2 + Na]+, 391.1669; found, 391.1670. 2-Cinnamyl-1,3-bis(4-methoxyphenyl)propane-1,3-dione (6k). This compound was prepared according to the general procedure B to provide 6k as a colorless oil (36.0 mg, 90% yield) after purification by silica gel column chromatography, with 9−12% EtOAc in PE as eluent (elution gradient). 1H NMR (400 MHz, CDCl3): δ 7.97 (d, J = 8.9 Hz, 4H), 7.27−7.22 (m, 4H), 7.19−7.16 (m, 1H), 6.91 (d, J = 8.9 Hz, 4H), 6.47 (d, J = 15.8 Hz, 1H), 6.28−6.20 (m, 1H), 5.23 (t, J = 6.5 Hz, 1H), 3.83 (s, 6H), 3.00 (t, J = 6.8 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 194.1, 163.8, 137.1, 132.2, 130.9, 129.0, 128.4, 127.2, 127.1, 126.1, 114.0, 57.2, 55.5, 33.1. IR (KBr): 745, 842, 1027, 1168, 1261, 1599, 1685, 2365, 2839, 2935. HRMS (ESI+): calcd for [C26H24O4 + Na]+, 423.1567; found, 423.1568. 2-Cinnamyl-1,3-bis(naphthalen-2-yl)propane-1,3-dione (6l). This compound was prepared according to the general procedure B to provide 6l as a colorless oil (35.3 mg, 80% yield) after purification by silica gel column chromatography, with 5−7% EtOAc in PE as eluent (elution gradient). 1H NMR (400 MHz, CDCl3): δ 8.55 (s, 2H), 8.06 (dd, J = 8.6, 1.4 Hz, 2H), 7.88−7.80 (m, 6H), 7.60 (t, J = 7.6 Hz, 2H), 7.52 (t, J = 7.6 Hz, 2H), 7.24 (dt, J = 14.8, 6.7 Hz, 4H), 7.18−7.14 (m, 1H), 6.54 (d, J = 15.8 Hz, 1H), 6.38−6.30 (m, 1H), 5.66 (t, J = 6.7 Hz, 1H), 3.18 (t, J = 6.8 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 195.5, 136.9, 135.7, 133.4, 132.5, 132.4, 130.5, 129.7, 128.9, 128.8, 128.4, 127.7, 127.3, 126.9, 126.8, 126.1, 124.1, 57.7, 33.2. IR (KBr): 745, 820, 1123, 1176, 1278, 1466, 1689, 2366, 3057. HRMS (ESI+): calcd for [C32H24O2 + Na]+, 463.1669; found, 463.1665.

Article

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.organomet.7b00284. Optimization conditions, synthesis of the substrates, 1H NMR monitoring experiments, mechanistic experiments, control experiments, characterization data, and 1H NMR and 13C NMR spectra of the compounds (PDF)

■

AUTHOR INFORMATION

Corresponding Author

*E-mail for Q.K.: [email protected]. ORCID

Qiang Kang: 0000-0002-9939-0875 Notes

The authors declare no competing financial interest.

■

ACKNOWLEDGMENTS This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences, Grant No. XDB20000000, and the 100 Talents Programme of the Chinese Academy of Sciences.

■

REFERENCES

(1) For selected reviews on transition-metal-catalyzed allylic substitutions, see: (a) Trost, B. M.; van Vranken, D. L. Chem. Rev. 1996, 96, 395−422. (b) Trost, B. M.; Crawley, M. L. Chem. Rev. 2003, 103, 2921−2944. (c) Helmchen, G.; Dahnz, A.; Dübon, P.; Schelwies, M.; Weihofen, R. Chem. Commun. 2007, 675−691. (d) Lu, Z.; Ma, S. Angew. Chem., Int. Ed. 2008, 47, 258−297. (e) Sundararaju, B.; Achard, M.; Bruneau, C. Chem. Soc. Rev. 2012, 41, 4467−4483. (f) Zhuo, C.X.; Zheng, C.; You, S.-L. Acc. Chem. Res. 2014, 47, 2558−2573. (g) Koschker, P.; Breit, B. Acc. Chem. Res. 2016, 49, 1524−1536. (2) For selected recent examples of palladium-catalyzed allylic alkylation to give selectively the branched products, see: (a) Trost, B. M.; Jäkel, C.; Plietker, B. J. Am. Chem. Soc. 2003, 125, 4438−4439. (b) Zhang, P.; Brozek, L. A.; Morken, J. P. J. Am. Chem. Soc. 2010, 132, 10686−10688. (c) Chen, J.-P.; Ding, C.-H.; Liu, W.; Hou, X.-L.; Dai, L.−X. J. Am. Chem. Soc. 2010, 132, 15493−15495. (d) Trost, B. M.; Malhotra, S.; Chan, W. H. J. Am. Chem. Soc. 2011, 133, 7328−7331. (e) Chen, J.−P.; Peng, Q.; Lei, B.−L.; Hou, X.−L.; Wu, Y.−D. J. Am. Chem. Soc. 2011, 133, 14180−14183. (f) Trost, B. M.; Xie, J.; Sieber, J. D. J. Am. Chem. Soc. 2011, 133, 20611−20622. (3) For selected examples of rhodium-catalyzed allylic alkylation to give selectively the branched products, see: (a) Evans, P. A.; Nelson, J. D. J. Am. Chem. Soc. 1998, 120, 5581−5582. (b) Evans, P. A.; Uraguchi, D. J. Am. Chem. Soc. 2003, 125, 7158−7159. (c) Hayashi, T.; Okada, A.; Suzuka, T.; Kawatsura, M. Org. Lett. 2003, 5, 1713−1715. (d) Ashfeld, B. L.; Miller, K. A.; Martin, S. F. Org. Lett. 2004, 6, 1321− 1324. (e) Evans, P. A.; Lawler, M. J. J. Am. Chem. Soc. 2004, 126, 8642−8643. (f) Kazmaier, U.; Stolz, D. Angew. Chem., Int. Ed. 2006, 45, 3072−3075. (g) Evans, P. A.; Oliver, S.; Chae, J. J. Am. Chem. Soc. 2012, 134, 19314−19317. (4) For selected examples of iridium-catalyzed regioselective allylic alkylation, see: (a) Lipowsky, G.; Miller, N.; Helmchen, G. Angew. Chem., Int. Ed. 2004, 43, 4595−4597. (b) Obora, Y.; Hatanaka, S.; Ishii, Y. Org. Lett. 2009, 11, 3510−3513. (c) Ye, K.−Y.; He, H.; Liu, W.−B.; Dai, L.−X.; Helmchen, G.; You, S.−L. J. Am. Chem. Soc. 2011, 133, 19006−19014. (d) Liu, W.−B.; Zheng, C.; Zhuo, C.−X.; Dai, L.− X.; You, S.−L. J. Am. Chem. Soc. 2012, 134, 4812−4821. (e) Hamilton, J. Y.; Sarlah, D.; Carreira, E. M. Angew. Chem., Int. Ed. 2013, 52, 7532− 7535. (f) Liu, W.−B.; Reeves, C. M.; Virgil, S. C.; Stoltz, B. M. J. Am. Chem. Soc. 2013, 135, 10626−10629. (g) Chen, W.; Hartwig, J. F. J. Am. Chem. Soc. 2013, 135, 2068−2071. (h) Krautwald, S.; Sarlah, D.; G

DOI: 10.1021/acs.organomet.7b00284 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics Schafroth, M. A.; Carreira, E. M. Science 2013, 340, 1065−1068. (i) Obora, Y.; Sawaguchi, T.; Tsubakimoto, K.; Yoshida, H.; Ogawa, S.; Hatanaka, S. Synthesis 2013, 45, 2115−2119. (j) Liang, T.; Zhang, W.; Krische, M. J. J. Am. Chem. Soc. 2015, 137, 16024−16027. (5) For selected examples of ruthenium-catalyzed regioselective allylic alkylation, see: (a) Mbaye, M. D.; Demerseman, B.; Renaud, J. L.; Toupet, L.; Bruneau, C. Angew. Chem., Int. Ed. 2003, 42, 5066− 5068. (b) Bruneau, C.; Renaud, J. L.; Demerseman, B. Chem. - Eur. J. 2006, 12, 5178−5187. (c) Sundararaju, B.; Achard, M.; Demerseman, B.; Toupet, L.; Sharma, G. V. M; Bruneau, C. Angew. Chem., Int. Ed. 2010, 49, 2782−2785. (d) Park, B. Y.; Nguyen, K. D.; Chaulagain, M. R.; Komanduri, V.; Krische, M. J. J. Am. Chem. Soc. 2014, 136, 11902− 11905. (e) Chen, Q. A.; Cruz, F. A.; Dong, V. M. J. Am. Chem. Soc. 2015, 137, 3157−3160. (f) Liang, T.; Nguyen, K. D.; Zhang, W.; Krische, M. J. J. Am. Chem. Soc. 2015, 137, 3161−3164. (g) Liang, T.; Zhang, W.; Chen, T.-Y.; Nguyen, K. D.; Krische, M. J. J. Am. Chem. Soc. 2015, 137, 13066−13071. (6) For selected examples of other metal catalyzed branch selective allylic alkylations, see the following. For Co, see: (a) Bhatia, B.; Reddy, M. M.; Iqbal, J. Tetrahedron Lett. 1993, 34, 6301−6034. For W, see: (b) Lloyd-Jones, G. C.; Pfalz, A. Angew. Chem., Int. Ed. Engl. 1995, 34, 462−464. For Fe, see: (c) Plietker, B. Angew. Chem., Int. Ed. 2006, 45, 1469−1473. For Mo, see: (d) Trost, B. M.; Miller, J. R.; Hoffman, C. M. J. Am. Chem. Soc. 2011, 133, 8165−8167. (7) Trost, B. M.; Brieden, W.; Baringhaus, K. H. Angew. Chem., Int. Ed. Engl. 1992, 31, 1335−1336. (8) (a) Yamamoto, Y.; Al-Masum, M.; Asao, N. J. Am. Chem. Soc. 1994, 116, 6019−6020. (b) Kadota, I.; Shibuya, A.; Gyoung, Y. S.; Yamamoto, Y. J. Am. Chem. Soc. 1998, 120, 10262−10263. (c) Lutete, L. M.; Kadota, I.; Yamamoto, Y. J. Am. Chem. Soc. 2004, 126, 1622− 1623. (d) Patil, N. T.; Kadota, I.; Shibuya, A.; Gyoung, Y. S.; Yamamoto, Y. Adv. Synth. Catal. 2004, 346, 800−804. (e) Patil, N. T.; Yamamoto, Y. J. Org. Chem. 2004, 69, 6478−6481. (f) Patil, N. T.; Khan, F. N.; Yamamoto, Y. Tetrahedron Lett. 2004, 45, 8497−8499. (g) Patil, N. T.; Song, D.; Yamamoto, Y. Eur. J. Org. Chem. 2006, 2006, 4211−4213. (9) Kim, I. S.; Krische, M. J. Org. Lett. 2008, 10, 513−515. (10) For addition of O-nucleophiles, see: (a) Lumbroso, A.; Koschker, P.; Vautravers, N. R.; Breit, B. J. Am. Chem. Soc. 2011, 133, 2386−2389. (b) Koschker, P.; Lumbroso, A.; Breit, B. J. Am. Chem. Soc. 2011, 133, 20746−20749. (c) Gellrich, U.; Meißner, A.; Steffani, A.; Kahny, M.; Drexler, H. J.; Heller, D.; Plattner, D. A.; Breit, B. J. Am. Chem. Soc. 2014, 136, 1097−1104. (d) Koschker, P.; Kähny, M.; Breit, B. J. Am. Chem. Soc. 2015, 137, 3131−3137. (11) For addition of S-nucleophiles, see: (a) Xu, K.; Khakyzadeh, V.; Bury, T.; Breit, B. J. Am. Chem. Soc. 2014, 136, 16124−16127. (b) Pritzius, A. B.; Breit, B. Angew. Chem., Int. Ed. 2015, 54, 3121− 3125. (c) Pritzius, A. B.; Breit, B. Angew. Chem., Int. Ed. 2015, 54, 15818−15822. (12) For addition of N-nucleophiles, see: (a) Cooke, M. L.; Xu, K.; Breit, B. Angew. Chem., Int. Ed. 2012, 51, 10876−10879. (b) Xu, K.; Thieme, N.; Breit, B. Angew. Chem., Int. Ed. 2014, 53, 2162−2165. (c) Xu, K.; Thieme, N.; Breit, B. Angew. Chem., Int. Ed. 2014, 53, 7268−7271. (d) Li, C.; Kahny, M.; Breit, B. Angew. Chem., Int. Ed. 2014, 53, 13780−13784. (e) Xu, K.; Gilles, T.; Breit, B. Nat. Commun. 2015, 6, 7616−7623. (f) Xu, K.; Raimondi, W.; Bury, T.; Breit, B. Chem. Commun. 2015, 51, 10861−10863. (g) Haydl, A. M.; Xu, K.; Breit, B. Angew. Chem., Int. Ed. 2015, 54, 7149−7153. (13) (a) Li, C.; Breit, B. J. Am. Chem. Soc. 2014, 136, 862−865. (b) Beck, T. M.; Breit, B. Org. Lett. 2016, 18, 124−127. (c) Beck, T. M.; Breit, B. Eur. J. Org. Chem. 2016, 2016, 5839−5844. (d) Cruz, F. A.; Chen, Z.; Kurtoic, S. I.; Dong, V. M. Chem. Commun. 2016, 52, 5836−5839. (e) Li, C.; Grugel, C. P.; Breit, B. Chem. Commun. 2016, 52, 5840−5843. (f) Cruz, F. A.; Dong, V. M. J. Am. Chem. Soc. 2017, 139, 1029−1032. (g) Beck, T. M.; Breit, B. Angew. Chem., Int. Ed. 2017, 56, 1903−1907. (14) (a) Gao, S.; Wu, Z.; Fang, X.; Lin, A.; Yao, H. Org. Lett. 2016, 18, 3906−3909. (b) Yang, C.; Zhang, K.; Wu, Z.; Yao, H.; Lin, A. Org.

Lett. 2016, 18, 5332−5335. (c) Gao, S.; Liu, H.; Wu, Z.; Yao, H.; Lin, A. Green Chem. 2017, 19, 1861−1865. (15) For selected examples of a carboxylic acid as cocatalyst, see: (a) Lumbroso, A.; Abermil, N.; Breit, B. Chem. Sci. 2012, 3, 789−793. (b) Chen, Q. A.; Chen, Z.; Dong, V. M. J. Am. Chem. Soc. 2015, 137, 8392−8395. (16) It should be noted that only one diastereomer was isolated and characterized. We could not rule out the formation of another diastereomer in this reaction. (17) (a) Watson, I. D. G.; Yudin, A. K. J. Am. Chem. Soc. 2005, 127, 17516−17529. (b) Ohshima, T.; Miyamoto, Y.; Ipposhi, J.; Nakahara, Y.; Utsunomiya, M.; Mashima, K. J. Am. Chem. Soc. 2009, 131, 14317− 14328. (c) Dubovyk, I.; Watson, I. D. G.; Yudin, A. K. J. Org. Chem. 2013, 78, 1559−1575.

H

DOI: 10.1021/acs.organomet.7b00284 Organometallics XXXX, XXX, XXX−XXX