Conversion of 1,4-Diketones into para-Disubstituted Benzenes

Abstract

Reaction of acetylides with aldehydes to form but-2-yne-1,4-diols, followed by triple bond reduction and oxidation of the hydroxyl groups, gives 1,4-diketones; these react with vinyllithium, and the resulting diols undergo ring-closing metathesis to form 2-cyclohexene-1,4-diols. Dehydration, usually by acid treatment, then gives benzenes carrying substituents in a 1,4 relationship. Use of substituted vinyllithiums provides further substitution on the final benzene rings. The method can be applied to the synthesis of C5-aryl carbohydrates.

Facile Regio- and Stereoselective Hydrometalation of Alkynes with a Combination of Carboxylic Acids and Group 10 Transition Metal Complexes: Selective Hydrogenation of Alkynes with Formic Acid

“…1,4-diphenethylbenzene (6n) 18 1 H NMR (400 MHz, CDCl 3 ): 7.33-7.21 (m, 10H), 7.14 (s, 4H), 2.94 (s, 8H). 13…”

Nitroalkenes as Latent 1,2-Biselectrophiles – A Multicatalytic Approach for the Synthesis of 1,4-Diketones and Their Application in a Four-Step One-Pot Reaction to Polysubstituted Pyrroles

“… Alternative nucleophilic acylations are reported with in situ generated acyl radicals or via Pd-mediated carbonylative 1,4-additions. , The reverse approach (route B ) using homoenolate equivalent synthons together with electrophilic acyl derivatives has also been established. Coupling of two C2 subunits according to pathway C requires the reactivity reversal of the carbonyl’s α-position, while functionalization of a 1,2-dianion (route E ) can be achieved with alkynes or as recently shown by the group of Bertus by a titanium mediated formal insertion of 1,2-dianions into acyl cyanohydrins . However, the need for elaborate precursors, harsh reaction conditions as well as limitation to nonfunctionalized or only symmetrical 1,4-diketones are among the drawbacks of the current methodologies.…”

“…Apart from their abundant occurrence in natural products and their significance as synthetic precursors for 1,4-diols, they have witnessed great interest especially for the construction of heteroaryl subunits, which are privileged motifs in medicinal as well as material chemistry. 1 Following classical Paal−Knorr conditions, 2 a wide range of five-membered heterocycles, 3 such as furans, pyrroles, and thiophenes, can be conveniently accessed as other routes allow for the synthesis of cyclopentenones, benzenes, 4 and biphenols. 5 Due to this prevalence and to exploit the great versatility of this precursor, numerous competent synthetic protocols have been developed, 6,7 albeit all of them with specific limitations.…”

Expedient Synthesis of C‐Aryl Carbohydrates by Consecutive Biocatalytic Benzoin and Aldol Reactions

“…The synthesis of C ‐aryl carbohydrate derivatives is a complex task that requires a number of cumbersome protection and deprotection steps 3a. 5 The stereoselective aldol addition reaction constitutes a straightforward and efficient bottom‐up approach for the de novo construction of carbohydrate‐like scaffolds 1b. 6 In that respect, biocatalytic carboligation reactions have been recognized as a powerful methodology for such transformations due to their high selectivity, their catalytic efficiency, and the often uncompromised stereoselectivity 7.…”