Diversity‐Oriented Synthesis of Chlorinated Arenes by One‐Pot Cyclizations of 4‐Chloro‐1,3‐bis(trimethylsilyloxy)buta‐1,3‐dienes

Abstract

A variety of 3‐chlorosalicylates were prepared by one‐potcyclizations of the first reported 4‐chloro‐1,3‐bis(trimethylsilyloxy)buta‐1,3‐dienes with various 1,3‐dielectrophiles. These include cyclizations with 3‐silyloxy‐2‐en‐1‐ones, 3‐aryl‐3‐silyloxy‐2‐en‐1‐ones, 1‐methoxy‐1‐en‐3‐ones, 1,1‐bis(methylthio)‐1‐en‐3‐ones, 3‐oxo orthoesters, 1,1,3,3‐tetraethoxypropanes, 1,1‐diacetylcyclopropane, and 3‐formylchromones. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Synthesis of Chlorinated Arenes and Hetarenes by One-Pot Cyclizations of 1,3-Bis-silyl Enol Ethers

“…36 The reaction of 4-chloro-1,3-bis(trimethylsilyloxy)buta-1,3-diene 15b with 3-oxoorthoesters 18a-j, following our previously established methodology, 37 furnished 3-chloro-4-methoxysalicylates 19a-j in 36-67% yield (Scheme 9). 36 The desired products, containing a chlorine atom and a methoxy group located at the meta and para position of the ester group, respectively, were regioselectively formed.…”

“…4-Chloro-1-methoxy-1,3-bis(silyloxy)-1,3butadienes 15a,b were obtained by deprotonation of 3-silyloxy-2-en-1-ones 14a,b with LDA at -78 °C and subsequent addition of trimethylchlorosilane (Scheme 6). 35,36 The resulting chlorinated dienes 15a , b are stable enough to be stored for several weeks under inert atmosphere and can be used as building blocks.…”

“…The reaction of chlorinated 1,3-bis(silyloxy)-1,3-dienes 15a,b with various 1,3-dielectrophiles as reaction partners resulted in formation of various chlorosalicylate derivatives through one-pot cyclizations. 36 For example, the TiCl 4 -mediated [3+3] cyclization of 4-chloro-1,3-bis(silyloxy)-1,3-di-ene 15a with 3-silyloxy-2-en-1-ones 16a-g, prepared by silylation of the corresponding 1,3-diketones, afforded 3chlorosalicylates 17a-g (Scheme 7). The product formation can be rationalized by conjugate addition of the terminal carbon atom of 15 onto 16 and subsequent cyclization.…”

Ethyl 4-chloro-2′-fluoro-3-hydroxy-5-methylbiphenyl-2-carboxylate

“…Functionalized chloroarenes are of considerable pharmacological relevance. 3-Chlorosalicylates and related compounds are employed as pharmacological agents (Wolf et al, 2009).…”

“…Experimental: The title compound was prepared according to a previously published procedure (Wolf et al 2009). To a CH 2 Cl 2 (6 ml) solution of 1-(2-fluoro-phenyl)-3-trimethylsilanyloxy-but-2-en-1-one (720 mg, 2.8 mmol) and 4-chloro-1ethoxy-1,3-bis-trimethylsilanyloxy-buta-1,3-diene (970 mg, 3.1 mmol) was added TiCl 4 (0.34 ml, 3.1 mmol) at 195 K under argon atmosphere.…”