Recent Advances in the Transition-Metal-Catalyzed Regioselective Approaches to Polysubstituted Benzene Derivatives

Abstract

Metalation−electrophilic fluorination of TMS-and TIPS-protected 1,3-benzothiazol-2-yl (BT) propargyl sulfones gave corresponding BT fluoropropargyl sulfones, Julia−Kocienski reagents for the synthesis of fluoro enynes. Both reagents reacted with aldehydes under mild DBU-or LHMDS-mediated conditions, giving high yields of conjugated fluoro enynes with E-stereoselectivity. In comparison to DBU-mediated reactions, stereoselectivity was higher in low-temperature LHMDS-mediated reactions. Two ketones were shown to react as well, using LHMDS as base. In situ removal of the TMS group gave terminal conjugated 2-fluoro 1,3-enynes. Synthetic utility of the fluoro enynes was demonstrated by conversion to internal alkynes and to stereoisomeric fluoro dienes via Sonogashira and Heck couplings.

Terminal Alkyne Coupling Reactions through a Ring: Mechanistic Insights and Regiochemical Switching

“…These reactions involve the formal addition of the C(sp)−H bond of one alkyne across the C≡C bond of the other, a process that can in principle result in three different regio‐ or stereochemical isomers: gem ‐, E ‐, and Z ‐enynes. With the additional possibility for the substrates to be consumed through competing metal‐catalysed reaction pathways—for instance leading to butatrienes, arenes, or other polyenes—the widespread application of terminal alkyne coupling reactions in organic synthesis rests on the development of catalysts that can enforce high reaction control 1, 3. Despite the evaluation of a variety of transition‐metal complexes, this remains a largely unfulfilled aspiration, with few catalysts capable of producing single enyne isomers with sufficiently high selectivity 4…”

Development of New Cycloaddition Reactions Based on the Unique Reactivity of Unsaturated Hydrocarbons

“…A large number of unique and efficient reactions developed by organometallic chemists has been widely used for the synthesis of various organic compounds such as drugs, natural products, and functionalized materials. The catalytic coupling reactions between unsaturated hydrocarbons such as cyclotrimerization of alkynes [1][2][3][4][5][6][7] and Diels-Alder-type reactions 3,4) are particularly attractive, since complicated molecules are obtained in one step from simple unsaturated hydrocarbons, which are usually less reactive compared to compounds bearing leaving groups such as a halogen atom (Chart 1). The reactions proceed with high atom economy 8) : the product incorporates all of the atoms of the substrates and no unwanted products (such as inorganic salts) are produced, which is another attractive feature.…”

π-Conjugated carbocycles and heterocycles via annulation through C-H and X-Y activation across CC triple bonds

“…Accordingly, a number of structurally interesting -conjugated molecules have been synthesized in the past few years (Figure 1), 1 and new methods including transition metal-catalyzed reactions have been developed for synthesizing those compounds efficiently and easily. In general, polysubstituted benzenes can be synthesized through the transition metalcatalyzed [2+2+2] cyclotrimerization of alkynes, [2][3][4][5][6][7][8][9][10] the Diels-Alder reaction of conjugated 1,3-dienes with alkynes, [11][12][13][14][15][16][17] the dihydro-Diels-Alder reaction [18][19][20][21][22][23][24][25][26] and the [4+2] benzannulation of conjugated enynes and diynes. However, these standard benzannulation reactions have not been used so often for the synthesis of -conjugated carbo-and hetero-cycles, perhaps because those structures (as shown in Scheme 1) are too complicated, preventing the application of simple benzannulation procedures.…”