Polyenes, tandem cyclizations

Tandem cyclization reactions to form polycyclic structures have also been reported (Schemes 6.87 and 6.88). Some of these reactions can strongly resemble the polyene cyclizations that lead to steroids. Further ene-yne reactions can be found in Section 6.2.5. 

Antibody HA519A4 catalyzes the tandem cationic cyclization of a polyene substrate (Figure 5). ... 

In addition to cationic cyclizations, other conditions for the cyclization of polyenes and of ene-ynes to steroids have been investigated. Oxidative free-radical cyclizations of polyenes produce steroid nuclei with exquisite stereocontrol. For example, treatment of (259) and (260) with Mn(III) and Cu(II) afford the D-homo-5a-androstane-3-ones (261) and (262), respectively, in approximately 30% yield. In this cyclization, seven asymmetric centers are established in one chemical step (226,227). Another intramolecular cyclization reaction of iodo-ene poly-ynes was reported using a carbopaUadation cascade terminated by carbonylation. This carbometalation—carbonylation cascade using CO at 111 kPa (1.1 atm) at 70°C converted an acycHc iodo—tetra-yne (263) to a D-homo-steroid nucleus (264) [162878-44-6] in approximately 80% yield in one chemical step (228). Intramolecular aimulations between two alkynes and a chromium or tungsten carbene complex have been examined for the formation of a variety of different fiised-ring systems. A tandem Diels-Alder—two-alkyne annulation of a triynylcarbene complex demonstrated the feasibiHty of this strategy for the synthesis of steroid nuclei. Complex (265) was prepared in two steps from commercially available materials. Treatment of (265) with Danishefsky s diene in CH CN at room temperature under an atmosphere of carbon monoxide (101.3 kPa = 1 atm), followed by heating the reaction mixture to 110°C, provided (266) in 62% yield (TBS = tert — butyldimethylsilyl). In a second experiment, a sequential Diels-Alder—two-alkyne annulation of triynylcarbene complex (267) afforded a nonaromatic steroid nucleus (269) in approximately 50% overall yield from the acycHc precursors (229). 

Kano S, Yuasa Y, Yokamatsu T, Asami K, Shiroshi S (1986) Effect of A-strain on synthesis of cis-fiised 4a-aryloctahydro—lH-cyclopenta[c]pyridine derivatives through tandem radical cyclization of an a-acylamino-polyene system. J Chem Soc Chem Commun 1717-1718... 

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