Synthesis of substituted tropones by sequential Rh-catalyzed [5+2] cycloaddition and elimination

Abstract

Highly substituted tropones are prepared from cycloheptatrienes derived from Rh-catalyzed intermolecular [5+2] cycloaddition of 3-acyloxy-1,4-enynes and propargylic alcohols. The intermolecular [5+2] cycloaddition is highly regioselective for a variety of propargylic alcohols. Elimination of the cycloaddition products afforded various substituted tropones.

Synthesis of Substituted Tropones and Advancement for the Construction of Structurally Significant Skeletons

“…The cycloheptatrienes were prepared from the [5+2] cycloaddition of 3‐acyloxy‐1,4‐enynes 20 and propargylic alcohols 21 using Rhodium catalyst (Scheme 5) (Table 1). [76] High regioselectivity was also observed herein the synthesis for a diverse set of propargylic alcohols. Various cycloadducts 22 were afforded from different propargylic alcohols 21 in presence of Wilkinson's catalyst providing good yield of 55–73 %.…”

Asymmetric Total Synthesis of Phomarol

“…Notably, this work represents the first example to construct the benzene ring by aromatization after the intramolecular oxidopyrylium ylide [5 + 2] cycloaddition. [31][32][33][34][35][36][37][38][39][40][41][42][43][44][47][48][49][50][51] Next (Scheme 4), compound 28 was treated with N-bromosuccinimide (NBS) for bromohydroxylation of the double bond, followed by the cyclization using KOH as a base, to give the desired epoxide 29 in 66% yield. Regioselective reductive cleavage of the epoxide in 29 with LiAlH 4 , followed by MOM protection and TIPS deprotection, afforded 30 in an overall yield of 71%.…”

Recent Developments in the [5+2] Cycloaddition

“…Using this methodology, these authors developed a novel route to prepare substituted tropones which are known to exhibit a broad spectrum of pharmaceutical activities. [78] Indeed, a wide range of these products were generated by transformation of cycloheptatrienes derived from rhodium-catalyzed intermolecular [5+ +2] cycloadditions of 3-acetyl-1,4-enynes 101 with propargylic alcohols 102. As shown in Scheme 33, the reaction performed with 5 mol% of Wilkinsons catalyst in chloroform at 65 8C led to the expected cycloheptatrienes 103 as single regioisomers in good yields (62-73%).…”