Palladium(0)‐Catalyzed Regioselective Synthesis of Macrocycles from Allenes with a Nucleophilic Functionality and Organic Iodides

Abstract

A highly regioselective synthesis of 15–20‐membered macrocycles via Pd(0)‐catalyzed coupling cyclization of allenes bearing a carbon or nitrogen nucleophilic functionality and organic iodides is reported. After oxidative addition and carbopalladation, anti‐π‐allyl palladium intermediates were formed, which was followed by the exclusive intramolecular nucleophilic attack at the terminal carbon atom of the allene moiety to afford products with yields ranging from 44–92% and E/Z ratios of up to 97/3.magnified image

Palladium-Catalyzed Cascade Annulation/Allylation of Alkynyl Oxime Ethers with Allyl Halides: Rapid Access to Fully Substituted Isoxazoles

“…R f = 0.30 (PE/EA = 60:1); it is obtained in 95% yield and as white solid, 124 mg, mp 100−101 °C; 1 H NMR (400 MHz, CDCl 3 ): δ 7.78 (d, J = 6.8 Hz, 2H), 7.70 (dd, J = 6.4, 3.0 Hz, 2H), 7.47 (dd, J = 6.4 Hz, 6H), 6.15−6.04 (m, 1H), 5.25 (d, J = 10.4 Hz, 1H), 5.09 (d, J = 17.2 Hz, 1H), 3.46−3.39 (m, 2H); 13 C{ 1 H} NMR (100 MHz, CDCl 3 ): δ 166. 8,164.0,135.4,129.8,129.6,129.4,128.9,128.7,128.4,128.2,126.9,117.1,110.1,27.1;IR (KBr) ν max /cm −1 : 3066, 2916, 2845, 1963, 1891, 1815, 1624, 1422, 1261, 1167, 1071, 922, 838, 757, 694, 583, 484 NO, 262.1226;found, 262.1229. 4-Allyl-5-phenyl-3-(p-tolyl)isoxazole (3ab). Following Typical Procedure II, the reaction of Pd(OAc) 2 (3 mol %, 3.375 mg), n-Bu 4 NBr (1.0 equiv, 161 mg), DMF (1.0 mL), 1ab (125.4 mg, 0.5 mmol), and 2a (72 mg, 0.6 mmol) afforded 3ab.…”

“…As an important chemical transformation type, nucleopalladation of unsaturated hydrocarbons, such as halopalladation, aminopalladation, and oxypalladation, has been established in recent years, which can undergo different quenching manners to break the carbon–palladium bond and generate diverse useful frameworks. In particular, the nucleopalladation of alkynes affords a highly reactive and crucial alkenylpalladium intermediate, which can be captured by the activated alkenes, carbon monoxide, allenes, enols, and other participants, providing the corresponding alkyl–Pd intermediates. Classically, there are three main approaches applied to quench the alkyl–Pd species: (i) β–H elimination to give an alkene; (ii) β-heteroatom elimination also to afford an alkene; (iii) reductive elimination to generate a saturated C–X bond.…”

Palladium-catalysed formation of vicinal all-carbon quaternary centres via propargylation

“…(2) The 1,6-allenyne derivative 3ja and ( S )- 3ga could go through a thermal [2+2] reaction 34 35 to construct the tricyclic product 13ja containing two highly strained four-membered rings and bicyclic product ( S )- 13ga containing one highly strained four-membered ring in very high yields. (3) In addition, the hydrogenation or semi-hydrogenation of the carbon–carbon triple bond in ( S )- 3gj afforded saturated ( S )- 14 under 15 mol% of Pd/C catalyst or ( S,Z )- 15 with a Z -double bond under 10 mol% of the Lindlar catalyst, respectively 36 37 .…”

Heck Macrocyclization in Forging Non-Natural Large Rings including Macrocyclic Drugs

“…Intrigued by this finding, the authors performed a follow-up study to show the opportunity of creating C 2v -symmetric macrocycles 71 and 72 through a fourfold Heck reaction with p-diiodobenzene and m-diiodobenzene, respectively [115]. More recently, this methodology was upgraded to embrace intermolecular cyclization between organoiodides and allenes (Figure 10 top), where the allene coupling partner A was equipped distally with an extra nucleophile X so as to self-trap the transient allylpalladium species B generated from initial addition of Ar-Pd-I, resulting in C with high regio-and E/Z stereoselectivity, finally yielding the saturated ring D via Pd/C hydrogenation [103,104]. A variety of unprecedented 9-20-membered rings were prepared via this strategy, as showcased in Figure 10 (bottom).…”