Catalytic Alkynylation of Cyclic Acetals and Ketals Enabled by Synergistic Gold(I)/Trimethylsilyl Catalysis

Abstract

A completely regioselective and challenging gold(I)-catalyzed ring-opening of cyclic 1,3-dioxolanes and dioxanes by trimethylsilyl alkynes to set diol-derived propargyl trimethylsilyl bis-ethers is reported. This unprecedented and not trivial transformation does not operate with the catalytic methodologies recently reported for catalytic alkynylation of acyclic acetals/ketals, and is uniquely enabled by the application of a recently introduced synergistic gold(I)-silicon catalysis concept capable of producing simultaneously catalytic amounts of two key players, a silicon-based Lewis superacid and a nucleophilic gold acetylide.

Nanoporous Aluminosilicate-Catalyzed Telescoped Acetalization-Direct Aldol Reactions of Acetals with 1,3-Dicarbonyl Compounds

“…We next studied the scope of the addition reaction with an extended range of acetal substrates. No significant reaction was observed with cyclic acetals, presumably due to the increased stability of these substrates, 28 and only starting material was obtained in the reaction of 2-phenyl-1,3-dioxane with AcAc. In line with previous literature reports, the reaction of simple acetals derived from alkyl acetals, such as valderaldehyde diethyl acetal, provided only small quantities of the desired addition product on reaction with AcAc.…”

“…Our interest in this area was prompted by the observation that acyclic acetals undergo direct aldol reactions with activated methylene compounds in the presence of strong Lewis acids at very low reaction temperatures to give the corresponding addition products (Scheme ). The reaction of carbonyl derivatives, such as acetals and acylals, as surrogates for carbonyl compounds is a surprisingly mature area , and is a useful strategy for carbon–carbon bond formation albeit one that has been comparatively under exploited. − …”

Synthesis of Propargylic Ethers by Gold-Mediated Reaction of Terminal Alkynes with Acetals

“…The most fundamental means to introduce alkyne moiety to an organic molecule is a reaction of metal acetylides with electrophiles. [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] For example, metal acetylides prepared by reacting terminal acetylenes with lithium, 3) magnesium, 4) zinc, 5) tin, 6) boron, 7) aluminum, 8) and titanium 9) reagents react with carbonyl compounds or acetals to produce propargylic alcohol or ether, respectively. However, these methods require a strong base or a stoichiometric amount of metal to generate metal acetylides.…”

“…On the other hand, the addition of terminal acetylene to acetals proceeds in the presence of a catalytic amount of zinc, 10,11) copper, 12) and tin 13) reagents to afford propargylic ether, although these reactions often require heating conditions and would not be applied to acid-sensitive substrates. Based on the high functional group compatibility, [14][15][16][17] gold catalyzed synthesis of propargylic alcohol 18) or ether 19) from terminal alkyne has recently been developed. However, in these reactions, electrophiles are only limited to aryl aldehydes.…”