Gold-catalyzed reactivity of 3-silyloxy-1,5-enynes: a synthetic tool for the synthesis of complex structures and its limitations

Gold(I)‐Catalyzed Synthesis of Highly Substituted 2‐Cyclopentenones from 5‐Siloxypent‐3‐en‐1‐ynes

“…[6,7] A remarkable feature of this reaction is that even poorly reactive Osilyl ethers can add efficiently to the alkynes in the presence of cationic gold(I) complexes. [8] In an effort to extend the scope of the reactions initiated by this intriguing siloxycyclization, we considered a catalytic reaction of 5-siloxypent-1-ynes 1 (Scheme 1). In this scenario, initial siloxycyclization of 1 followed by the ionization of C À O bond generates a carbocation intermediate B. Intramolecular carbocyclization and the subsequent elimination of cationic gold(I) via a cyclic intermediate C with the assistance of iPrOH will produce highly substituted cyclopentanone 2.…”

Total Synthesis of (+)-Sieboldine A: Evolution of a Pinacol-Terminated Cyclization Strategy

“…Our success in constructing sieboldine A in this way required that the hydroxy group of the tethered hydroxylamine be masked with a protecting group (methoxymethyl) that did not decrease the reactivity of the nitrogen and could be removed in the presence of the delicate the bicyclo[5.2.1]decane- N , O -acetal moiety. The synthesis also illustrates the use of Au(I)-catalyzed activation of an alkyne to promote a cyclization-pinacol sequence, first introduced by Rhee and Kirsch, 71 which in demanding contexts can be superior to Lewis acid-activation of an acetal.…”

“…71 The requisite alkyne precursor 71 was synthesized in 90% yield by homologation of aldehyde 65 with 1.6 equiv of the Ohira–Bestmann reagent (Scheme 18). 72 Exposure of 1,6-enyne 71 to 10 mol% of PPh 3 Au + SbF 6 − and 1.1 equiv of i -PrOH in CH 2 Cl 2 (Table 3, Entry 2) yielded a 1:1 ratio of the desired pinacol-terminated cyclization product 72 and byproduct 73 73 resulting from a Claisen-terminated heterocyclization pathway ( J → L → 73 ).…”

“…74 A trend similar to that reported by Kirsch and Rhee was observed wherein electron-rich gold(I) complexes improved the selectivity for the pinacol-terminated cyclization. 71a Using [( t -Bu) 2 P( o -biphenyl)]AuSbF 6 the pinacol-terminated product 72 and byproduct 73 were formed in a >10:1 ratio (Table 3, Entry 8). Computational studies by Toste, Goddard et al have suggested that the steric size of the 2-(di- tert -butylphosphino)biphenyl ligand inhibits back-bonding stabilization between the metal center and the alkyne, effectively increasing the carbocationic nature of the gold alkyne species.…”

When Alkyne π-Activation Meets Pinacol-Type [1,2]-Rearrangement: On the Invention of Domino Reactions for the Synthesis of Carbocycles and Heterocycles

“…Scheme 3 Planned domino reaction consisting of a 6-endo carbocyclization and a 1,2-alkyl shift To our delight, our studies were facilitated by the fact that a variety of starting 3-silyloxy-1,5-enynes can be easily accessed through a general synthesis route starting from the corresponding enals or enones. 19 As exemplified in Scheme 4, 3-silyloxy-1,5-enyne 9 was prepared on a large scale and in good overall yield from cyclohex-1-ene-1-carbaldehyde (6). Secondary alcohol 7 was obtained in 93% yield through 1,2-addition, in the presence of catalytic amounts of mercury(II) chloride and iodine, of a Grignard reagent derived from propargyl bromide.…”