Stereoselective Synthesis of Substituted Oxocene Cores by Lewis Acid Promoted Cyclization

Abstract

Substituted oxocene derivatives have been synthesized by Lewis acid catalyzed reactions of ε-hydroxy-alkene and substituted aromatic aldehydes. The Cu(OTf)2-bis-phosphine catalyzed reaction typically provides substituted dihydropyran derivatives through an olefin-migration, followed by a Prins cyclization. The corresponding reaction catalyzed by TMSOTf or BF3·OEt2 provided eight-membered cyclic ethers, oxocenes, selectively. This methodology provides convenient access to a variety of 2,4,8-trisubstituted oxocenes in good yields and excellent diastereoselectivities.

Lewis Acid Mediated Cyclizations: Diastereoselective Synthesis of Six- to Eight-Membered Substituted Cyclic Ethers

“…Based upon this result, we elected to investigate BF 3 •OEt 2 as catalyst in our cyclization of 5a and p-nitrobenzaldehyde. 40 The results are summarized in Table 5. The reaction of alkenol 5a and p-nitrobenzaldehyde in the presence of 3 equivalents of BF 3 •OEt 2 in t-BuOMe at 0 °C resulted in the formation of oxocene derivative 22a and a new exoolefin derivative 31a in a 76:24 ratio and 33% combined…”

“…The use of 0.2 equivalents of BF 3 •OEt 2 in CH 2 Cl 2 provided the best results with an endo/exo-olefin oxocene ratio of 98:2 and a modest yield of 38% (entry 3). 40 In 2011, Cho and co-workers reported TMSOTf-catalyzed Prins-type cyclization, leading to oxepane derivatives. 41 We therefore explored TMSOTf-catalyzed reactions, aiming to improve the yield of oxocene product 22a.…”

“…Further support of the structural assignment was obtained by determination of the X-ray crystal structure of the corresponding sulfonamide derivative of the major oxocene product 22a. 40 In efforts to expand our cyclic ether synthetic method, seven-membered oxepines have been synthesized. Using 5methylhex-5-en-2-ol (34), TMSOTf, 4 Å molecular sieves, and a variety of aldehydes, oxepines were synthesized with high diastereoselectivity (dr >20:1), with an unidentified minor isomer.…”

An Efficient Synthesis of Benzazocines by Gold(I)‐Catalyzed Tandem 1,2‐Acyloxy Shift/[3+2] Cycloaddition of Terminal 1,9‐Enynyl Esters

“…[1] Eight-membered rings, especially nitrogen-containing heterocycles, are particularly ubiquitous and are essential structural elements for pharmaceutical agentsand biologically active natural and unnatural alkaloids, such as otonecine, [2] buflavine (1), which was isolated from Boophane flava, [3] and (À)-steganacin aza analogues (Figure 1). [4] With the development of organic chemistry,v arious methods for preparing eight-membered rings have been developed, including ring expansions, [5] cycloadditions, [6] intramolecular acetal-alkene cyclizations, [7] inter-molecular cyclization, [8] and the most versatile ring-closing metathesis (RCM) reactions. [9] Although there are many reported methods to construct eight-membered rings, methods to assembleb enzo-fused, eight-membered, N-heterocyclic rings (i.e.,b enzazocines) remained few.…”

Visible-Light-Induced External Radical-Triggered Annulation To Access CF2-Containing Benzoxepine Derivatives

“…Unlike five- and six-membered cyclic ethers, the construction of seven-membered ethers may be more problematic due to unfavorable entropic penalties and transannular interactions associated with their formation . While challenging, the synthesis of benzoxepines has attracted intensive efforts to answer the needs of synthetic and medicinal chemistry.…”