Palladium-catalyzed enantioselective decarboxylative allylic alkylation of fully substituted <i>N</i>-acyl indole-derived enol carbonates

Alexy, Eric J.; Fulton, Tyler J.; Zhang, Haiming; Stoltz, Brian M.

doi:10.1039/c9sc01726g

Cited by 40 publications

(20 citation statements)

References 34 publications

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“…N-Acylpyrroles (A) [9], N-acylpyrazoles (B) [10], N-acylindoles (C) [11,9e], and N-acylindolines (D) [12,9g] (Scheme 1(b)), a class of heterocyclic tertiary amides, have been proved to be versatile building blocks in organic synthesis in general [9][10][11][12], and in asymmetric synthesis [9][10][11][12] in particular. It was envisioned that this class of amides are more reactive than common amides, and the catalytic transformation would be feasible [13].…”

Section: Introductionmentioning

confidence: 99%

Ni-catalyzed direct alcoholysis of N-acylpyrrole-type tertiary amides under mild conditions

Chen

Huang

2020

Sci. China Chem.

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N-Acylpyrrole-type amides are a class of versatile building blocks in asymmetric synthesis. We report that by employing Ni(COD) 2 /2,2′-bipyridine (5 mol%) catalytic system, the direct, catalytic alcoholysis of N-acylpyrrole-type aromatic and aliphatic amides with both primary and secondary alcohols can be achieved efficiently under very mild conditions (rt, 1 h) even at gram scale. By increasing the catalyst loading to 10 mol%, prolonging reaction time (18 h), and/or elevating reaction temperature to 50°C/80°C, the reaction could be extended to both complex and hindered N-acylpyrroles as well as to N-acylpyrazoles, Nacylindoles, and to other (functionalized) primary and secondary alcohols. In all cases, only 1.5 equiv. of alcohol were used. The value of the method has been demonstrated by the racemization-free, catalytic alcoholysis of chiral amides yielded from other asymmetric methodologies.

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Section: Introductionmentioning

confidence: 99%

Ni-catalyzed direct alcoholysis of N-acylpyrrole-type tertiary amides under mild conditions

Chen

Huang

2020

Sci. China Chem.

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“…Additionally, Stoltz and Zhang demonstrated these conditions can be applied to the selective enolization and trapping of a variety of acyclic a-aryl substituted carboxylic acid derivatives including a-ethyl-a-phenyl t-butyl, phenyl, and ethyl esters. 14 Enolization with LiHMDS (entry 2) and KHMDS (entry 3) without additives results in identical yields and diastereoselectivity. Notably, phthalimide protected amino acid 15a is obtained without column chromatography and the relative stereochemistry was confirmed unambiguously by X-ray crystallography, matching the computationally predicted outcome.…”

Section: Resultsmentioning

confidence: 93%

Global Diastereoconvergence in the Ireland–Claisen Rearrangement of Isomeric Enolates: Synthesis of Tetrasubstituted -Amino Acids

Fulton¹,

Cusumano²,

Alexy³

et al. 2020

Preprint

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<div><div><div><p>A dual experimental/theoretical investigation of the Ireland–Claisen rearrangement of tetrasubstituted a-phthalimido ester enolates to afford a-tetrasubstituted, b-trisubstituted a-amino acids (generally >20:1 dr) is described. For trans allylic olefins, the Z and E-enol ethers proceed through chair and boat transition states, respectively. For cis allylic olefins, the trend is reversed. As a result, the diastereochemical outcome of the reaction is preserved regardless of the geometry of the enolate or the accompanying allylic olefin. We term this unique convergence of all possible olefin isomers as global diastereoconvergence. This reaction manifold circumvents limitations in present-day technologies for the stereoselective enolization of a,a-disubstituted allyl esters. Density func- tional theory paired with state-of-the-art local coupled-cluster theory (DLPNO-CCSD(T)) was employed for the accurate determina- tion of quantum mechanical energies.</p></div></div></div>

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“…3, 46.4, 42.8, 28.3;IR (Neat Film, NaCl) 2978, 2926, 1694, 1450, 1414, 1393, 1367, 1329, 1246, 1152, 1042 To a 20 mL vial containing allyl ester 2c (320 mg, 0.740 mmol, 1.0 equiv) and NaH (60% dispersion in mineral oil, 32.5 mg, 0.814 mmol, 1.1 equiv) was added THF (7.4 mL, 0.1 M) at 23 °C. After stirring for 30 min, Selectfluor™ (315 mg, 0.889 mmol, 1.2 equiv) was added in a 4,155.0,131.3,130.8,126.1,119.8,113.9,95.7 (dd,14.6 Hz),81.5,67.3,55.5,47.5 (dd, J C-F = 109.0, 23.7 Hz), 47.2 (d, J C-F = 92.2 Hz), 43. 4, 28.3;IR (Neat Film, NaCl) 2976, 2936, 2844, 1759, 1698, 1603, 1578, 1512, 1449, 1414, 1367, 1327, 1258, 1168, 1151, 1076, 1030 6-allyl 1-(tert-butyl) 4-(4-methoxybenzoyl)-5-oxo-6-(prop-2-yn-1-yl)-1,4-diazepane-1,6-…”

Section: -Allyl 1-(tert-butyl) 6-benzyl-4-(4-methoxybenzoyl)-5-oxo-1mentioning

confidence: 99%

Palladium-Catalyzed Decarboxylative Asymmetric Allylic Alkylation of 1,4-Diazepan-5-ones

2019

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Materials and Methods Unless otherwise stated, reactions were performed in flame-dried glassware under an argon or nitrogen atmosphere using dry, deoxygenated solvents. Solvents were dried by passage through an activated alumina column under argon. 1 Reaction progress was monitored by thinlayer chromatography (TLC) or Agilent 1290 UHPLC-MS. TLC was performed using E. Merck silica gel 60 F254 precoated glass plates (0.25 mm) and visualized by UV fluorescence quenching or KMnO 4 staining. Silicycle SiliaFlash® P60 Academic Silica gel (particle size 40-63 nm) was used for flash chromatography. 1 H NMR spectra were recorded on Varian Inova 500 MHz, Varian 400 MHz, and Bruker 400 MHz spectrometers and are reported relative to residual CHCl 3 (δ 7.26 ppm). 13 C NMR spectra were recorded on a Varian Inova 500 MHz spectrometer (125 MHz), a Varian 400 MHz spectrometer (100 MHz), and Bruker 400 MHz spectrometers (100 MHz) and are reported relative to CHCl 3 (δ 77.16 ppm). Data for 1 H NMR are reported as follows: chemical shift (δ ppm) (multiplicity, coupling constant (Hz), integration). Multiplicities are reported as follows: s = singlet, d = doublet, t = triplet, q = quartet, p = pentet, sept = septuplet, m = multiplet, br s = broad singlet, br d = broad doublet. Data for 13 C NMR are reported in terms of chemical shifts (δ ppm) Some reported spectra include minor solvent impurities of water (δ 1.56ppm), ethyl acetate (δ 4.12, 2.05, 1.26 ppm), methylene chloride (δ 5.30 ppm), acetone (δ 2.17 ppm), grease (δ 1.26, 0.86 ppm), and/or silicon grease (δ 0.07 ppm), which do not impact product assignments. Most NMR spectra are complicated by rotational isomerism about amide bonds. This behavior is illustrated by variabletemperature NMR spectra of compound 4e in DMSO (p. S102). IR spectra were obtained by use of a Perkin Elmer Spectrum BXII spectrometer or Nicolet 6700 FTIR spectrometer using thin films deposited on NaCl plates and reported in frequency of absorption (cm-1). Optical rotations were measured with a Jasco P-2000 polarimeter operating on the sodium D-line (589 nm), using a 100 mm path-length cell. Analytical SFC was performed with a Mettler SFC supercritical CO 2 analytical chromatography system utilizing Chiralpak (AD-H, ASH or IC) or Chiralcel (OD-H, OJ-H, or OB-H) columns (4.6 mm x 25 cm) obtained from Daicel Chemical Industries, Ltd. High resolution mass spectra (HRMS) were obtained from Agilent 6200 Series TOF with an Agilent G1978A Multimode source in electrospray ionization (ESI+), atmospheric pressure chemical ionization (APCI+), or mixed ionization mode (MM: ESI-APCI+). Absolute stereochemistry is assigned by analogy to previous results by our group. 2 Supporting Information for Sercel, ‡ Sun, ‡ and Stoltz S3 Reagents were purchased from commercial sources and used as received unless otherwise stated. Ligands (S)-(CF 3) 3-t-BuPHOX and (S)-Ty-PHOX were prepared according to literature procedures. 3,4

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Palladium-catalyzed enantioselective decarboxylative allylic alkylation of fully substituted N-acyl indole-derived enol carbonates

Cited by 40 publications

References 34 publications

Ni-catalyzed direct alcoholysis of N-acylpyrrole-type tertiary amides under mild conditions

Ni-catalyzed direct alcoholysis of N-acylpyrrole-type tertiary amides under mild conditions

Global Diastereoconvergence in the Ireland–Claisen Rearrangement of Isomeric Enolates: Synthesis of Tetrasubstituted -Amino Acids

Palladium-Catalyzed Decarboxylative Asymmetric Allylic Alkylation of 1,4-Diazepan-5-ones

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