Synthetic Applications of o- and p-Halobenzyl Sulfones as Zwitterionic Synthons:  Preparation of Ortho-Substituted Cinnamates and Biarylacetic Acids

Abstract

The synthetic applications of o-halobenzyl and p-halobenzyl sulfones as precursors of 1,3- and 1,5-zwitterionic synthons, respectively, are described. Their alpha-sulfonyl carbanions, generated by means of the phosphazene base P2-Et or BuLi or K2CO3 under PTC conditions, reacted with different electrophiles such as alkyl halides, aldehydes, and electrophilic olefins. Palladium-catalyzed cross-coupling processes such as Heck, Suzuki, and Sonogashira reactions can be efficiently performed at the halogen atom. These two sequential functionalization processes are applied to the synthesis of ortho-substituted cinnamates and pharmaceuticals belonging to the family of p-biarylacetic acids such as 4-biphenylacetic acid, namoxyrate, xenyhexenic acid, and biphenylpropionic acid.

False‐negative core needle biopsies of the breast

“…Complex 4g was a very useful catalyst for the preparation of biphenylmethyl p ‐tolyl sulfone via the Suzuki–Miyaura reaction of the corresponding aryl bromide in organic solvents,36 which represents a very practical precursor of functionalized 4‐biarylacetic acids.…”

Synthesis of Xenbucin using Suzuki reaction catalyzed by Pd/C in water

“…When the reaction was completed, sat. NH 4 Cl was added. The reaction mixture was poured in water and extracted with ether (3 x 20 mL).…”

“…The combined ether fractions were washed with water (20 mL) and brine (20 mL). The organic phase was dried over MgSO 4 , and solvents were removed under reduced pressure. The product was purified with column chromatography (Hex/ EtOAc7:1).…”

“…After reaction was completed, the mixture was acidified using 3 M HCl. Product was extracted with ethylacetate and the combined EtOAc fractions were washed with brine and dried over MgSO 4 …”

“…Cavallini et al, on the other hand, reported the preparation from commercially available 4-biphenylylactonitrile [3]. Recently, 1 was also prepared using a zwitterionic technique, where the biaryl moiety was prepared using a Suzuki reaction [4]. Total yields in these reactions were low overall (20 -35%).…”