Oxidopyrylium -based 5+2 -cycloaddition

The total synthesis of natural products hainanolidol and harringtono-lide was realized featuring two stereoselective [3,3]-sigmatropic rearrangements, and an oxidopyrylium-based [5 + 2] cycloaddition to construct the tetracyclic carbon skeleton and the tetrahydrofuran unit (13JA12434). 

Scheme 43.25 Enantioselective oxidopyrylium-based [5+2] cycloadditions by dual catalysis.

In 2011, Jacobsen et al. [38] reported a dual catalyst system consisting of a chiral primary amine thiourea and an achiral thiourea that promoted an intramolecular variant of the oxidopyrylium-based [5-1-2] cycloaddition reaction with high enanti-oselectivity (Scheme 43.25). Initially, poor enantioselectivity (21% ee) was obtained in the presence of catalyst 119. Subsequent studies showed that the addition of an achiral thiourea catalyst 120 dramatically improved the reaction enantioselectivily (67% ee, entry 2, Table 43.1). Further optimization led to the identification of 121, which bears a 2,6-diphenylanilide component, as the most enantioselective ami-nothiourea catalyst (88% ee, entry 3, Table 43.1). A clear and dramatic cooperative effect between the optimal catalysts was supported by a series of experiments. With optimal catalytic conditions, valuable tricyclic stractures were obtained in moderate to good yields and with high enantioselectivities (up to 95% ee) (Scheme 43.25). 

When the pyrone 297 was exposed to base in dichloromethane, formation of the oxidopyrylium occurs and subsequent cycloaddition transpires. Lee found that when the allene tether was 3 (n = 0), cycloaddition occurs to form the bicy-clo[5.3.0]decadiene 298 exclusively, rather than the alternative bicyclo[5.2.0] nonadiene product 299. Increasing the tether length by one resulted in formation of the exo-substituted double bond (299) in 45% yield. Increasing the tether length by one carbon, to four, completely retarded the cycloaddition (Scheme 4.83). 

The [6+3] cycloaddition of 6,6-diarylfiilvenes to 3-oxidopyrylium betaines, derived by the action of base on 6-acetoxy-6//-pyran-3-ones, gives access to fused oxa-bridged cyclooctanoids (Scheme 23) <06T5952>. 

Wender extended the studies of the intramolecular cycloaddition by examining substituted oxidopyrylium intermediates with stereocenters in the tethers [58 a]. Pyran 44 underwent smooth cycloaddition with complete stereoselectivity to give 45 due to the methyl group at Cn assuming an equatorial position in the chair-like conformation of the olefinic side-chain, Eq. 30. The stereocenter at Cn effectively controlled the stereochemistry at C6, C8, and C9. The reaction proceeded with heating or at room temperature with a catalytic amount of base. 

---