A Pericyclic Cascade to the Stereocontrolled Synthesis of 9-cis-Retinoids

Abstract

A domino reaction that is pericyclic in nature is thought to be triggered upon treatment of alkenynol 10 with arylsulfenyl chlorides. The process comprises an ordered sequence of sigmatropic rearrangements: a reversible [2,3]-allyl sulfenate to allyl sulfoxide shift, followed by a [2,3]-propargyl sulfenate to allenyl sulfoxide rearrangement, and last a stereodifferentiating [1,5]-sigmatropic hydrogen migration leading to polyene 13. The occurrence of the C7 to C11 hydrogen migration has been demonstrated by labeling experiments. The double diastereoselection of the [1,5]-sigmatropic hydrogen shift to afford a single isomer of the final polyene 13 is thought to arise from a combination of the electronic effect of the sulfoxide at one terminus, and the steric effect imparted by the bulky trimethylcyclohexenyl substituent at the other terminus. The overall process thus constitutes a stereoselective synthesis of an E,Z,Z-triene fragment from an alkenynol and, in particular, a retinoid with the 7E,9Z,11Z,13E configuration on the conjugated polyenic side chain. Application of this method to the synthesis of retinoids, including labeled analogues, is straightforward.

Aromatischer Charakter elektrocyclischer und pseudopericyclischer Reaktionen: thermische Cyclisierung von (2Z)-Hexa-2,4,5-trienalen und ihren Schiff-Basen

“…Hierzu stellen wir im Folgenden einige Ringschlüsse von (2 Z )‐Hexa‐2,4,5‐trienalen und den zugehörigen Iminen vor (Schema ). Diese Verbindungen sind interessante Modellsysteme für die Untersuchung der chemischen Eigenschaften von Cumulenen und Retinoiden 5. Sie weisen neben den cumulierten Doppelbindungen ein Heteroatom an einem Ende des wechselwirkenden Systems auf.…”

On the Aromatic Character of Electrocyclic and Pseudopericyclic Reactions: Thermal Cyclization of (2Z)-Hexa-2,4-5-trienals and Their Schiff Bases

“…interesting model systems for the study of the chemistry of cumulenes and retinoids. [5] A common feature of these systems is the presence of a cumulene bond and a heteroatom at one end of the interacting system. This electronic array allows for either one or two orbital disconnections, that is, regions where orthogonal sets of orbitals meet but do not overlap at the transition state associated with their cyclization (see Scheme 2).…”

“…The high electron affinity of acene (E 1/2 À 1.65 V) [5] allows its reduction with activated metallic ytterbium or samarium, affording the ansa-lanthanocenes [(h 5 -C 12 H 8 ) 2 Ln(thf) 2 ] as dark red (Ln Yb, 1) or dark brown crystals (Ln Sm, 2) in yields of about 90 % (Scheme 1). The ytterbium and samarium are activated by addition of iodine to the respective molecular plane (Figure 4).…”

On the Aromatic Character of Electrocyclic and Pseudopericyclic Reactions: Thermal Cyclization of (2Z)-Hexa-2,4-5-trienals and Their Schiff Bases

“…[5] A common feature of these systems is the presence of a cumulene bond and a heteroatom at one end of the interacting system. interesting model systems for the study of the chemistry of cumulenes and retinoids.…”

“…The crude product was purified by column chromatography on silica gel 60 using ethyl acetate/MeOH ( interesting model systems for the study of the chemistry of cumulenes and retinoids. [5] A common feature of these systems is the presence of a cumulene bond and a heteroatom at one end of the interacting system. This electronic array allows for either one or two orbital disconnections, that is, regions where orthogonal sets of orbitals meet but do not overlap at the transition state associated with their cyclization (see Scheme 2).…”