Aldol-dehydration, double intramolecular

The final two stages are very straightforward. Oxidative scission of the C3-C5 double bond in 6 with ozone provides triketone 5 which, without purification, is subjected to a base-induced intramolecular aldol/dehydration reaction. The crystalline product obtained from this two-step sequence (45 % overall yield) was actually an 85 15 mixture of ( )-progesterone and a diastereomeric substance, epimeric at C-17. Two recrystallizations afforded racemic progesterone [( )-(1)] in diastereomerically pure form. 

The Robinson annulation has three distinct steps the Michael addition of the enol or enolate across the double bond of the a,(3-unsaturated ketone to produce a 1,5-diketone (Michael adduct), followed by an intramolecular aldol reaction, which affords a cyclic (3-hydroxy ketone (keto alcohol), and finally a base-catalyzed dehydration which gives rise to the substituted cyclohexenone. An alternative mechanism via disrotatory electrocyclic ring closure is possible. ... 

Unfortunately, most elimination reactions (Chapter 17) offer little control over the geometry of the product treating sec-butanol in acid, for example, gives mainly the more substituted 2-butene, but as a 3 1 mixture of geometrical isomers. But there are some important exceptions. If the product has the double bond inside a ring of less than eight members, it has to be a cis double bond. Examples include the simple dehydration of a cyclopentanol and an intramolecular aldol reaction. The six-membered ring is formed before the dehydration step. 

Taking all these results into consideration, the most plausible mechanism for VB A formation from 9 to 5 are illustrated in Figure 10. After the dehydration of the intramolecular aldol product [11], the double bond delocalized as 12 and the NADH-dependent enzyme delivered the hydride from the Si face at C4 or from the Re face at C3 (29). 

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