Gold‐ or Platinum‐Catalyzed Cascade Processes of Alkynol Derivatives Involving Hydroalkoxylation Reactions Followed by Prins‐Type Cyclizations

Abstract

An efficient method for the synthesis of [3.3.1]bicyclic compounds from easily available alkynol derivatives has been developed. The reaction is based on a gold- or platinum-catalyzed tandem process that involves an intramolecular hydroalkoxylation of a triple bond followed by a Prins-type cyclization. The reaction has been carried out with differently substituted alkynol derivatives and oxygen-, nitrogen-, and carbon-centered nucleophiles. The incorporation of halogen atoms as nucleophiles and elimination reactions has also been studied. Enantiomerically pure [3.3.1]bicyclic systems were easily synthesized from the chiral pool.

Gold(I)-Catalyzed Activation of Alkynes for the Construction of Molecular Complexity

“… 97 Shortly later, a gold(I)-catalyzed tandem intramolecular hydroalkoxylation/Prins-type cyclization was described, affording oxygen-containing [3.3.2] bicyclic compounds 58 diastereoselectively (Scheme 20 ). 98 …”

Copper‐Catalyzed Cascade Cyclization of Indolyl Homopropargyl Amides: Stereospecific Construction of Bridged Aza‐[n.2.1] Skeletons

“…PG = protecting group. In addition, amides containing different substituents on the indole ring also underwent smooth cascade cyclization,p roducing the corresponding 2f-n in good to excellent yields (entries [6][7][8][9][10][11][12][13][14], Finally,i tw as found that the reaction also occurred well with (S)-(+ +)-tert-butylsulfinamide-derived 1e' ',a nd thus the other enatiomer, 2e' ', was specifically produced (entry 15). Further screening of solvents such as toluene and chlorobenzene led to as lightly decreased yield (entries [14][15].…”

Copper‐Catalyzed Cascade Cyclization of Indolyl Homopropargyl Amides: Stereospecific Construction of Bridged Aza‐[n.2.1] Skeletons

“…for the synthesis of [3.2.1]bicyclic acetals, and notable is that endo ‐hydroalkoxylation was observed in case of internal akynes . In 2006, Barluenga and co‐workers reported an outstanding protocol for either the gold‐ or platinum‐catalyzed tandem exo ‐hydroalkoxylation/Prins‐type cyclization, leading to a variety of 9‐oxabicyclo[3.3.1]nonanes (Scheme c) . On the basis of this work, the relevant tandem exo ‐hydroalkoxylation/hydroarylation was further developed by the same group .…”

“…[7] Following this concept, transition-metalcatalyzed alkyne hydroalkoxylation-and hydroaminationinitiated cascade cyclizations have been well documented to be ap owerful method to synthesize av ariety of structurally complex heterocycles, [4] especially the valuable bridged heterocycles. [8][9][10][11] Fore xample,M ichelet and Genẽ tr eported in 2005 ag old-catalyzed tandem exo-hydroalkoxylation/ hydroalkoxylation of bis-homopropargylic diols,a llowing the facile formation of functionalized strained bicyclick etals (Scheme 1b). [8a] Ar elated platinum-catalyzed tandem cycloisomerization of alkyne diols was subsequently disclosed by Ley et al for the synthesis of [3.2.1]bicyclic acetals,a nd notable is that endo-hydroalkoxylation was observed in case of internal akynes.…”