Importance of the Halogen in the Competition Between Metal Halogen Exchange and 1,3-Elimination of 1-Halobicyclo(1.1.1)pentane

Abstract

1-Iodobicyclo[1.1.1]pentane reacts cleanly with t-butyllithium by a metal-halogen exchange process to give 1-lithiobicyclo[1.1.1]pentane. Both 1-chlorobicyclo[1.1.1]pentane and the parent hydrocarbon bicyclo [1.1.1]pentane are found to be inert to t-butyllithium.

Selected Topics in the Syntheses of Bicyclo[1.1.1]Pentane (BCP) Analogues

“…The most common pathway to achieve alkyllithium species by lithium‐halogen exchange proved most challenging as demonstrated by Della and co‐workers (Scheme C) . 1‐Chlorobicyclo[1.1.1]pentane ( 12 ) was inert towards lithium‐halogen exchange process . When 1‐bromobicyclo[1.1.1]pentane ( 13 ) was treated with tert ‐butyllithium ( t BuLi), the desired BCP−Li ( 9 ) intermediate was not observed .…”

“…Instead, an unexpected intermediate 15 was formed via the intermediacy of 2 . Only by utilizing the more reactive 1‐iodobicyclo[1.1.1]pentane ( 14 ), was BCP−Li ( 9 ) obtained …”

“…Among the three strategies, the lithium‐metalloid exchange process (Scheme B) should be the most efficient method to afford 9 , followed by the process of LiDBB reduction of 8 (Scheme A) and, finally, the lithium‐halogen exchange process (Scheme C) for the reasons listed below. First, most of the reported syntheses of 1‐halobicyclo[1.1.1]pentanes ( 12‐ ‐ 14 ) require Barton halo‐decarboxylation as the key step . This process usually requires multi‐step synthesis; moreover, the key intermediate, bicyclo[1.1.1]pentane‐1‐carboxylic acid ( 18 ), is most efficiently prepared using BCP−Li ( 9 , see Section 2.2) .…”

“…First, most of the reported syntheses of 1‐halobicyclo[1.1.1]pentanes ( 12‐ ‐ 14 ) require Barton halo‐decarboxylation as the key step . This process usually requires multi‐step synthesis; moreover, the key intermediate, bicyclo[1.1.1]pentane‐1‐carboxylic acid ( 18 ), is most efficiently prepared using BCP−Li ( 9 , see Section 2.2) . The only exception is that 1‐chlorobicyclo[1.1.1]pentane ( 12 ), the inactive analogue, could be achieved in 1 step from 2 by hydrogen atom transfer chemistry .…”

“…Compared to the previous two synthetic strategies, the idea of trapping BCP−Li ( 9 ) with carbon dioxide appears to be more straight‐forward. Indeed, two route have been proposed by Wiberg (Scheme C) and Della (Scheme D) independently. Wiberg's strategy utilized the sulfide 8 as the source for BCP−Li (Scheme C) .…”