Brominated β-Alkoxyvinyl Trihalomethyl Ketones as Promising Synthons in Heterocyclic Synthesis

Abstract

<jats:p>5-Bromo- and 5,5-dibromo-1,1,1-trihalo-4-methoxypent-3-en-2-ones (brominated enones) have proven to be attractive building blocks for the construction of heterocyclic and polyheterocyclic compounds bearing a trihalomethyl moiety through interesting cyclocondensation, alkylation, and cycloaddition reactions. This review compiles all of the reactions conducted with these brominated enones since they were first disclosed in 2001.</jats:p><jats:p>1 Introduction</jats:p><jats:p>2 Synthesis and Initial Applications</jats:p><jats:p>3 Synthesis Using First-Generation Intermediates</jats:p><jats:p>4 Synthesis Using Second-Generation Intermediates</jats:p><jats:p>5 Synthesis Using Third-Generation Intermediates</jats:p><jats:p>6 Conclusions</jats:p>

The Wonderful World of β‐Enamino Diketones Chemistry

“…Speaking in terms of reactivity toward a nitrogen nucleophile (e.g., hydrazine or amines), according to reports in the literature for parent structures, the 1,4‐conjugated addition is expected to occur first, followed by nucleophilic addition at the carbonyl carbon. [ 27–31 ] This may become an issue when dealing with the 1,3‐diketone, given that there are two carbonyls that may experience the addition, which could furnish a mixture of two products (Scheme 3).…”

Divergent and Regioselective Synthesis of (Trifluoromethyl/carboxyethyl)benzo[4,5]imidazo[1,2‐a]pyrimidines from β‐Enamino Diketones

“…[ 13–17 ] Despite the existing methods that present feasible synthetic routes, some of them still lack regioselectivity – a major problem when dealing with possible drug candidates. [ 18 ] To overcome the selectivity issue, β‐enamino diketones (see Scheme 1) have emerged as suitable starting materials for the synthesis of several heterocyclic scaffolds, due to presenting high selectivity in most of the cyclocondensation reactions performed. [ 19–21 ] Even though the chemistry of carboxyethyl β‐enamino diketones 1 has been explored, [ 22–29 ] trifluoromethyl 2 ones have been far less used in heterocyclic synthesis.…”

Trifluoromethyl β‐Enamino Diketones as Dual Substrates for the Synthesis of 5‐Benzoyl‐6‐(trifluoromethyl)pyrimidines and their Pyrimidin‐4(3H)‐one Analogues

“…[4,5] Trifluoromethyl -enaminones have been widely used in the construction of several heterocyclic scaffolds such as pyrimidines [6] and azoles, [7,8] 1,4-diazacycles, [9] 1H-pyrroles [10,11] and others. [12] Its application was also demonstrated in the synthesis of aliphatic functionalized compounds. [13][14][15] Trifluoromethylenamino diketones 1 (Scheme 1), which are prepared from the C-acylation reaction of -dimethylamino ketones ( -enaminones) with trifluoroacetic anhydride, are promising building blocks for type [3+2] or [3+3] cyclocondensation reactions, given that they are highly functionalized structures composed of three electrophilic centers that can furnish three different heterocyclic scaffolds, for cyclocondensation reactions with NCN-dinucleophiles for example (see Scheme 1).…”

“…Trifluoromethyl β‐enaminones have been widely used in the construction of several heterocyclic scaffolds such as pyrimidines and azoles,, 1,4‐diazacycles, 1 H ‐pyrroles, and others . Its application was also demonstrated in the synthesis of aliphatic functionalized compounds .…”

“…Hz, J = 0.6 Hz 1H, Ar), 7.67 (dd, J = 1.6 Hz, J = 0.7 Hz, 1H, Ar)8.03 (s 1H, H4), 9.09 (s, 1H, OH).13 C NMR (100 MHz, CDCl 3 ): δ 14.6 (SMe), 46.8 (C7), 84.5 (q, 2 J C-F = 33.9 Hz, C6), 106.2 (C5), 112.9 (Ar), 118.0 (C9), 122.9 (Ar), 124.2 (q, 1 J C-F = 293.9 Hz, CF 3 ), 133.1(C8), 146.9 (Ar), 150.9 (Ar), 151.9 (C4), 167.5 (C2), 183.7 (C=O). GC-MS (EI, 70 eV): m/z (%) 346 (1), 277 (66), 278 (10), (72), 289(38), 275 (52), 261(12), 181(24), 135 (100), 92(14), 77(19). Anal.…”