Bicyclo[3.2.1]octane Synthons from Cyclopropenes:  Functionalization of Cycloadducts by Nucleophilic Additions

Abstract

It has been known for several decades that a highly functionalized family of tetrahalobicyclo[3.2.1]octadienes are readily available through the cycloaddition of furan or cyclopentadiene with either tetrachloro- or tetrabromocyclopropene. However, the application of these highly functionalized building blocks in synthesis has remained relatively unexplored in relation to their better-known counterparts derived through oxyallyl cation additions. As a first step toward utilizing these highly versatile intermediates in synthesis, a study of the addition of various nucleophiles to the halogenated nucleus has been conducted. It has been found that these halogenated systems are amenable to a wide range of functionalizations in high yields and with good selectivities.

Halogenated Oxabicyclo[3.2.1]octadiene Building Blocks: Elaboration of the Dibromoenone

“…[a] Condition A: Pd(OAc) 2 and iodide showed almost the same reaction profile including rate and product yield in all of the palladium reactions examined. The formation of single regioisomers in the above reactions shows that the β position is significantly more reactive than the α-bromide.…”

“…Triethylamine (3 mL) was added foll owed by co pp er (i ) i od id e ( 9. 1 m g, 0.048 mmol) and Pd(dppf) 2 …”

“…Acetonitrile (9 mL) was added and the reaction mixture stirred at 25°C until all material was dissolved. Triethylamine (9 mL) was added followed by copper(i) iodide (48 mg, 0.25 mmol) and Pd(dppf) 2 To a 25 mL round-bottomed flask was added 11a (982 mg, 3.40 mmol). Dichloromethane (11 mL) was added and the reaction mixture was stirred at 25°C until all material was dissolved.…”

“…[1] Over the past several years we have studied the utility of this highly functionalized bicyclic nucleus as a versatile building block and have been interested in using this system in both targetoriented and diversity-oriented manifolds. [2] Recently, we developed a direct route to the chiral enones 2a/b from 1 involving the resolution of the corresponding tartrate ketals (Scheme 1). [3] Scheme 1.…”

The Cycloaddition Strategy for the Synthesis of Natural Products Containing Carbocyclic Seven‐Membered Rings

“…[23] These adducts are highly unstable and undergo a spontaneous rearrangement to the oxabicyclo-A C H T U N G T R E N N U N G [3.2.1]octadienes 59, likely through a carbonium ion intermediate. [24] The tetrabromoadduct can be converted into either isomer of the enantiomerically pure building blocks 60 through resolution of the corresponding tartrate ketals. [25] Elaboration of the unsubstituted olefin through a DielsAlder reaction [26] and the annulation of the dibromoenone through a chromium-mediated closure [27] has been used to generate the core structure of guanacastepene A.…”