Novel Building Blocks: 1‐Aryl‐2‐chloro‐1‐ethoxyethenes – Preparations and Transformations

Abstract

We described here a simple method for the preparation of 1‐aryl‐2‐chloro‐1‐ethoxyethenes 2a–u, which are prodrugs for Alzheimer's disease, by the reaction of dichloroacetaldehyde diethyl acetal with various aryl and alkenyllithium compounds in high yields. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Catalytic Friedel–Crafts Acylation and Benzoylation of Aromatic Compounds Using Activated Hematite as a Novel Heterogeneous Catalyst

“…2‐Chloro‐1‐(4‐methoxyphenyl)ethanone 41 (2b′): Compound 2b′ was obtained as a white solid in 91% yield; mp 96–97 °C; IR (KBr): ν=1693 (CO), 1599, 1513, 1266–1224 (CH 2 Cl), 1173, 1021 (C‐O), 845–820–781 (phenyl), 590 cm −1 ; 1 H NMR (250 MHz, CDCl 3 ): δ =3.89 (s, 3 H, 1 H), 4.66 (s, 2 H, 1 H), 6.97 (dd, 2 H, J 1 =7.0 Hz and J 2 = 2.0 Hz), 7.96 (dd, 2 H, J 1 =7.0 Hz and J 2 = 2.0 Hz); 13 C NMR (62.9 MHz, CDCl 3 ): δ =40.5, 45.6, 51.1, 55.5, 111.6, 114.1, 121.1, 130.9, 131.3, 134.8, 164.2, 172.2, 189.9.…”

Au‐Catalyzed Addition of Nucleophiles to Chloroalkynes: A Regio‐ and Stereoselective Synthesis of (Z)‐Alkenyl Chlorides

“…[5] The 2-chloroalkenyl ethers would be expected to be novel precursors for aryl chloromethyl ketones and a prodrug in the treatment of Alzheimer's disease by hydration. [2] In addition, alkenyl chlorides are commomly found in biologically active natural products. [6] So developing efficient synthetic approaches to construct functionalized alkenyl chlorides is one of the most exciting topics in organic synthesis.…”

“…Functionalized olefins are ubiquitous structures in organic chemistry because of its presence in natural and biologically active compounds and are very frequently encountered structural motifs in organic synthesis In this respect, multisubstituted alkenyl chlorides are valuable intermediates in organic synthesis because of their ability to serve as convenient substrates in hydration, amination and transition metal‐catalyzed cross‐coupling reactions, such as Buchwald–Hartwig aminations, Sonogashira couplings, Suzuki couplings, Stille couplings and so on. For example, the 2‐chloroalkenyl sulfides smoothly couple with aryl/alkylboronic acid with high chemoselectivity and efficience .…”

A Convenient Preparative Method for New 1,3‐Bis(hetaryl)‐2‐chloropropen‐1‐ones Using β‐Alkoxy‐α‐chloroalkenyllithium Compounds

“…We first prepared six kinds of 1-aryl-2-chloro-1-ethoxyethenes, 1-6, according to our original method as shown in Scheme 1. [10] Next, we performed the lithiation of 2-(2chloro-1-ethoxyethenyl)thiophene (1) and reaction with a variety of aldehydes and ketones. The lithiation of 1 with nBuLi proceeded at -78°C, and the successive reaction with benzaldehyde gave (Z)-2-(2-chloro-1-ethoxy-3-hydroxy-3phenylprop-1-enyl)thiophene (7a) in 85 % yield.…”

“…-1-ethoxy-3-hydroxy-3-(p-methoxyphenyl)prop-1enyl]furan(10): IR (KBr): ν = 3443 (OH),2932, 1612, 1511 (furyl), 1248, 1172, 1068, 1032 (C-O), 830, 748 (C-Cl) cm -1 1. H NMR (500 MHz, CDCl 3 ): δ = 1.31 (t, J = 7 Hz, 3 H, Me), 2.84 (d, J = 7 Hz, 1 H, OH), 3.77 (s, 3 H, OMe), 3.79-3.89 (m, 2 H, OCH 2 ), 6.15 (d, J = 7 Hz, 1 H CHOH), 6.46 (dd, J = 2, 3 Hz, 1 H, ArH), 6.86-6.88 (m, 3 H, ArH), 7.38 (d, J = 8 Hz, 2 H, ArH), 7.47 (d, J = 2 Hz, 1 H, ArH) ppm.…”