Intramolecular 1,3-diyl trapping reactions. Total synthesis of (.+-.)-hypnophilin and (.+-.)-coriolin. Formation of the trans-fused bicyclo[3.3.0]octane ring system

Abstract

The intramolecular 1,3-diyl trapping reaction served as the key step in a total synthesis of (±)-coriolin (1) and the first total synthesis of (±)-hypnophilin (3). In the process, four of the required eight (coriolin) or six (hypnophilin) stereocenters were established. The reaction was studied as a function of temperature. The highest yield and greatest stereo-/ regioselectivity was obtained when the reaction was initiated photochemically at -6(3 °C in methyl alcohol. From the temperature dependence, it was established that enthalpic rather than entropic factors were responsible for governing the selectivity of the process. The required cis, anti ring-fused product 10 was favored over the minor products by * = -2.19 kcal mol""1 2. Two noteworthy steps in the conversion of tricyclopentanoid 10 to the natural products included the Lewis acid facilitated 1,4-addition of Li2Cu(CN)(CH3)2 to the hindered C2 carbon in 26 and the epoxidation of compounds 10, 24, and 29. Each olefin 10 and 24 led to the formation of products containing both cis-and trans-fused bicyclo[3.3.0]octane ring systems. Molecular mechanics calculations (MM2) were used to calculate differences in strain energies between the two types of products. In the case of olefin 39, only the trans-fused AB-ring junction stereochemistry was observed. Single-crystal X-ray analysis verified the stereochemical assignments and served to provide a rationale for the unanticipated formation of these trans-fused products. ' UCSB.

Male-Produced Pheromone of Spathius agrili, A Parasitoid Introduced For The Biological Control Of The Invasive Emerald Ash Borer, Agrilus planipennis

“…Preparation of (Z)-10-bromodec-3-ene (13) and Grignard Reagent Hydrolysis of (Z)-7-decenyl acetate (11) to alcohol 12 was accomplished with methanolic KOH (Hijfte et al, 1987). Alcohol 12 was converted to bromide 13, without isomerization of the Z-double bond, by adding triphenylphosphine dibromide to CH 2 Cl 2 instead of generating it in situ (Kuklev and Smith, 2006).…”

Diyl Trapping and Electroreductive Cyclization Reactions

“…35 The ratio proved to be dependent upon the size of the OR unit appended to C 11 . When a bulky silyl ether was used (75), a single product formed, 77c.…”

“…We elected to synthesize racemic coriolin (15) 34 and hypnophilin (16), 34,35 being confident that enantiomerically pure materials could be assembled if desired.…”

The Versatile Trimethylenemethane Diyl; Diyl Trapping Reactions − Retrospective and New Modes of Reactivity

“…This is important, particularly within the context of applying the methodology to the total shows promise as an entry to the tumor-promoting phorbol esters. [22] synthesis of natural products possessing these skeletons [e.g., coriolin (13), [12] hypnophilin (14), [12] aphidicolin (55)], Scheme 12 or those that might be readily derived from them (e.g. 6).…”

“…2.5 m (13) [11] [12] and (d,l)-hypnophilin (14). [11] [12] Thus, irradiation of diazene 11 at 6°C through a Pyrex filter, led solution of the diazene was added slowly to a 51 m solution of allene in refluxing hexanes; similar results were obcleanly to the formation of 12 in an 84% yield.…”