Regiochemistry of the reaction of chromium-carbene complexes with acetylenes

Abstract

The decidedly interesting observation of the reaction of the chromium-carbene complex 1 with diphenylacetylene appeared in the literature in 1975.' This cyclization reaction occurs with incorporation of the acetylene and a carbon monoxide ligand to give the (naphthol)chromium tricarbonyl complex 2. We anticipate that this reaction will be synthetically valuable and are currently utilizing it in the synthesis of anthracyclines. We report here our results concerning the regiochemistry of this reaction and its extension to several carbene complexes bearing certain aryl substituents.1 2

Total synthesis of (±)-naphthacemycin A9, possessing both antibacterial activity against methicillin-resistant Staphylococcus aureus and circumventing effect of β-lactam resistance

“…The Dötz reaction between terminal alkynes and a chromium-carbene complex typically gives a single regioisomer; however, unsymmetrically substituted internal alkynes give mixtures of the two possible regioisomers. [29][30][31][32] On the other hand, incorporation of a boron unit into an unsymmetrically substituted internal alkyne is a rapid and efficient approach for the reliable and predictable synthesis of hydroquinone and quinone boronate esters, with excellent regioselectivity due to the Lewis acid/base interaction [CO → B(OR) 2 ] in the metallohexatriene intermediate, as shown in Scheme 1. [33][34][35] The substrate of the Dötz reaction can be prepared by Suzuki-Miyaura coupling between the corresponding D and E-ring units (16 and 17).…”

“…In addition, attempted Suzuki-Miyaura coupling of 20 with dimethoxybenzyl bromide under several conditions was also unsuccessful. Friedel-Crafts cyclization of 28 under acidic conditions identical to those used for the preparation of 22 as shown in Scheme 2 gave the cyclized compound (29) in 83% yield. Cyclized compound (29) contained an undesired spiro[4.5] frame and exhibited demethylation of the p-methoxy position of the A-ring.…”

“…Friedel-Crafts cyclization of 28 under acidic conditions identical to those used for the preparation of 22 as shown in Scheme 2 gave the cyclized compound (29) in 83% yield. Cyclized compound (29) contained an undesired spiro[4.5] frame and exhibited demethylation of the p-methoxy position of the A-ring. As compound 29 was selectively generated in our system, the formation of such a spirocyclic frame would be more preferable under Brønsted acid-mediated Friedel-Crafts cyclization, although Kende and co-worker reported an example of ring expansion in a spirocyclic frame via dienone-phenol rearrangements in several spirocyclic dienone derivatives in the presence of CF 3 CO 2 H in CH 2 Cl 2 .…”

Zirconacycle-mediated synthesis of carbocycles

“…Consequently, there is significant interest in the development of new synthetic methodologies to access higher para-quinones. Although a number of synthetic methods affording these molecules have been reported [77][78][79][80][81], the most attractive one seems to be the direct cycloaddition of metallacyclopentadienes to quinones. Reaction of zirconacyclopentadienes with quinones 9 in the presence of copper chloride and p-chloranil afforded para-dihydroquinones 10 and quinones 11 (Scheme 9) [82].…”

The Chromium‐Templated Carbene Benzannulation Approach to Densely Functionalized Arenes (Dötz Reaction)

“…One of the main features of the benzannulation reaction of Fischer carbene complexes is the regiochemistry of the incorporation of alkynes into the assembled hydroquinone [53]. While terminal alkynes are incorporated with high regioselectivity (regardless of alkyl and aryl substituents), internal alkynes are prone to much poorer regioselectivity.…”