A Facile Phenol-Driven Intramolecular Diastereoselective Thermal/Base-Catalyzed Dipolar [2 + 2] Annulation Reactions:  An Easy Access to Complex Bioactive Natural and Unnatural Benzopyran Congeners

Abstract

The complex bioactive natural and unnatural benzopyran congeners have been synthesized using one-/two-step approaches in very good yields from the reactions of two different dihydroxyphthalides, natural resorcyclic acid derivative, and trihydroxybenzophenone with citral and/or farnesal, via the phenol-driven intramolecular diastereoselective thermal/base-catalyzed dipolar [2+2] cycloaddition reactions and three different thermal intramolecular cyclization reactions. The effects of the nature and the position of phenolic groups in the starting materials on the course of these cycloaddition reactions have also been described. Depending upon the absence or presence of intramolecular hydrogen bonding of the phenolic group with the carbonyl moiety in the starting materials, these phenol-driven intramolecular thermal/base-catalyzed dipolar [2+2] cycloaddition reactions either furnished the kinetically controlled products or directly formed the thermodynamically controlled rearranged products, respectively.

Total Synthesis of Cytosporone B

“…Another attempt was then made with AlCl 3 . Despite an earlier report 24 of a similar reaction, the reagent could not give the deprotected product yet. The reaction proceeded difficultly and hence was abandoned.…”

Synthetic efforts toward [3.3.1] bridged bicyclic phloroglucinol natural products

“…Porco’s total synthesis of clusianone was initiated by transforming phloroglucinol ( 274 , Scheme 74), following a known 92 two-step sequence, into benzoylated pyrogallol product 275 . Bis -prenylation proceeded favorably to form pre-cyclization cascade precursor 276 .…”

Efficient Synthesis of Cylindol A and the Proposed Structure of Cylindol B: The Structure of Cylindol B Still in Question

“…Thus, bromination reaction of 2,2'-dihydroxy diphenyl ether (7) using NBS 2 provided para-substituted dibromide 8, the regioselectivity of which was confirmed by the coupling pattern of 1 H NMR spectrum: 6-H (dd, J = 6.2, 2.5 Hz) coupled with 2-H (d, J = 2.5 Hz) in long-range fashion and with 5-H (d, J = 6.2 Hz) vicinally (Scheme 2). After methylation of the phenol group of 8, methoxycarbonylation in the presence of (BINAP)PdCl 2 in methanol under 50 psi of carbon monoxide 3 gave diester 10, which was demethylated selectively by aluminum chloride 4 to provide cylindol A (1) in excellent overall 39% yield. Its spectroscopic data was consistent completely with that of the reported value.…”