Palladium-catalyzed carbocyclization of 1,6-enynes leading to six-membered rings or oxidized five-membered trifluoroacetates

Abstract

We describe palladium-catalyzed carbocyclization of 1,6-enynes leading to six-membered rings by water-originated hydride addition. Mechanistic features of this anomalous carbocyclization and isolation of a chiral five-membered C-Pd intermediate as an oxidized form of trifluoroacetate are also reported.T ransition metal-catalyzed carbocyclizations of 1,6-enynes A (1-4), such as cycloisomerization (5-11), metathesis (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22), skeletal reorganization (23-26), and ene reactions (27)(28)(29), are useful synthetic methods leading to five-membered rings (Scheme 1). By contrast, we challenged six-membered cyclization of 1,6-enynes of type B by alkyne-metal-or carbonyl (Y ϭ CAO)-Lewis acid complexation by 6-(2, 4) ene-type cyclization (30) (after [1,5]-hydrogen shift numbering) (Oppolzer's type II) (31) (Scheme 2). A six-membered ring was obtained, however, not as the expected (Z)-olefin C. Herein, we report that dicationic palladium-catalyzed carbocyclization of 1,6-enynes (32, 33), unlike ruthenium-, rhodium-, and platinum-catalyzed metathesis, leads to the (E)-six-membered rings (D), wherein water-derived hydride is involved to fix the (E)-olefin geometry. We also present the mechanistic features of this anomalous carbocyclization and isolation of a chiral five-membered C-Pd intermediate (E) as an oxidized trif luoroacetate. MethodsGeneral. 1 H, 13 C, and 31 P NMR spectra were measured on Varian Gemini 300 (300 MHz) and Varian Gemini 400 (400 MHz) spectrometers. IR spectra were measured on a FT͞IR-5000 spectrometer (Jasco, Tokyo). Optical rotations were measured on a Jasco DIP-370. Liquid chromatographic analyses (HPLC) were conducted on a Jasco PU-980, LG-980 -02, DG-980 -50, AS-950, and CO-966 instrument equipped with model UV-975 spectrometers as an ultraviolet light. Peak areas were calculated by JASCO-BORWIN (WINDOWS NT) as an automatic integrator. Capillary GC analyses were conducted on a Shimadzu GC-14B instrument by using N 2 (75 kPa) as a carrier gas. Peak areas were calculated by a Shimadzu C-R6A as an automatic integrator; chiral columns were CPCyclodextrin-␤-2,3,6-M-19 (i.d. 0.25 mm ϫ 25 m; Chrompack, GL Sciences, Tokyo) and CP-Chirasil-Dex CB (i.d. 0.32 mm ϫ 25 m; Chrompack, GL Sciences). The split ratio was 100:1. Analytical TLC was performed on glass plates (Merck Kieselgal 60 F 254 ; layer thickness, 0.25 and 0.2 mm). Visualization was accomplished by UV light (254 nm), anisaldehyde, KMnO 4 , and phosphomolybdic acid. Column chromatography was performed on Kanto Silica Gel 60N (spherical, neutral; Kanto Kagaku, Tokyo). All experiments were carried out under an argon atmosphere unless otherwise noted. 5,5Ј-diylbis(diphenylphosphine) [(S)-SEGPHOS] were provided by Takasago International (Tokyo).Typical Procedure for Pd-Catalyzed Ene-Type Cyclization. To a Pyrex test tube well degassed DMSO (2.0 ml) was injected, and argon was charged. [(MeCN) 4 Pd](BF 4 ) 2 (11.1 mg, 0.025 mmol) and (R)-BINAP (17.1 mg, 0.050 mmol) were added under an argon atmosphere, and the suspensi...

Asymmetric Au-catalyzed cycloisomerization of 1,6-enynes: An entry to bicyclo[4.1.0]heptene

“…( E )-1-Bromo-3-(3-(2-methyl-3-phenylallyloxy)prop-1-ynyl)benzene (2h): Following the same procedure as for the synthesis of 2f , in the presence of CuI (62 mg, 0.1 equiv) and PdCl 2 (PPh 3 ) 2 (115 mg, 0.05 equiv), 1-bromo-3-iodobenzene (0.53 mL, 1.3 equiv) in distilled diisopropylamine (6.8 mL), ( E )-(2-methyl-3-(prop-2-ynyloxy)prop-1-enyl)benzene [77] (611 mg, 1 equiv) was transformed to 2h (851 mg) in 76% yield. TLC (cyclohexane/ethyl acetate 90:10) R f 0.63; 1 H NMR (300 MHz, CDCl 3 ) δ 2.08 (d, J = 1.3 Hz, 3H), 4.31 (d, J = 0.8 Hz, 2H), 4.53 (s, 2H), 6.71 (d, J = 1.0 Hz, 1H), 7.30 (t, J = 7.8 Hz, 1H), 7.36–7.56 (m, 6H), 7.58 (dt, J = 8.0, 0.8 Hz, 1H), 7.75 (t, J = 1.6 Hz, 1H); 13 C NMR (75 MHz, CDCl 3 ) δ 16.0, 58.0 (2C), 85.1, 87.1, 122.5, 125.1, 127.0, 128.3, 128.5 (2C), 129.3 (2C), 130.1, 130.7, 132.0, 134.7, 134.9, 137.7.…”

Cycloisomerization of 1,n‐Enynes: Challenging Metal‐Catalyzed Rearrangements and Mechanistic Insights

“…In the presence of a Pd 0 precursor, such as [Pd 2 (dba) 3 ], substrate 72 was converted into cyclohexadiene 73 in 69 % yield in benzene at reflux [Eq. (25)]. On the basis of the regioselectivity of the reaction, a mechanism relying on the oxidative dimerization of the triple bonds to form a palladacyclopentadiene intermediate of type 74 has been proposed.…”

“…[25] For example, Hatano and Mikami described the synthesis of dihydropyran 35 from allylpropargyl ether 34 in the presence of a dicationic palladium/biphosphane system in DMSO as the solvent for 18 h at 100 8C [Eq. (13)].…”

Catalytic Conia-ene and related reactions

“…Studies with deuterium-labeled substrates revealed that the addition occurs in a trans fashion, thus the only suitable activation modes are either a pure alkyne activation or a dual activation by two metals. There is precedence on the formation of Pd-enolates and the coordination of Pd(II) to alkynes, however, based on previous studies, [71][72][73] the authors have ruled out the possibility that Pd(II) acts as soft-Lewis acids. Nonetheless, Balme and co-workers demonstrated that alkali metal enolates add to Pd(II)-activated alkynes.…”