Addition of aryl substituents to cyclohexadienyliron electrophiles in the development of routes to C12 central building blocks for alkaloid synthesis

Selective Synthesis and Reactivity of η5‐Arylcyclohexadienyliron Complexes

“…This provides general access to the 1-aryl-4-methoxy series. Our method [10] to prepare the parent phenyl-substituted example 53 with phenyllithium (70 % yield) was superior to the use of lithium diphenylcuprate (23 %) or diphenylzinc (11 %) and the step to remove the methoxy group was highly efficient (reaction with TFA/NH 4 PF 6 : 98 %). This successful approach [8,10] has now been extended to the 3',4'-methylenedioxy example 50 which has the correct aromatic substitution pattern (Scheme 6) for the alkaloid crinine.…”

“…Our method [10] to prepare the parent phenyl-substituted example 53 with phenyllithium (70 % yield) was superior to the use of lithium diphenylcuprate (23 %) or diphenylzinc (11 %) and the step to remove the methoxy group was highly efficient (reaction with TFA/NH 4 PF 6 : 98 %). This successful approach [8,10] has now been extended to the 3',4'-methylenedioxy example 50 which has the correct aromatic substitution pattern (Scheme 6) for the alkaloid crinine. [34] The required cyclohexadienyliron complex 50 was prepared by generation of the aryllithium reagent [36] from 3,4-methylenedioxybromobenzene, addition to the 1,4-dimethoxy salt 51 (59 %), and reaction with hexafluorophosphoric acid (89 %).…”

“…The enolate NaCH(CN)CO 2 Me was reacted with 50 to produce 58 in 68 % yield. In a trial series of experiments towards crinine, this successful formation of the required quaternary centre was also examined with the enolate NaCH(CN)CO 2 CH 2 CH 2 Si-A C H T U N G T R E N N U N G Me 3 [37] which we used in our work on the O-methyljoubertiamine [8] and lycoramine [10] targets. Addition to 50 proved similarly well regiocontrolled and gave 59 in 82 % yield.…”

“…The use of carbonyliron complexes in asymmetric synthesis continues to attract sustained attention [1] and forms the central strategy [2] in several recent target molecule syntheses [3,4] that build on the principles successfully established in examples employing cyclohexadienyliron complexes as controlled electrophiles to address stereochemical issues in routes to terpene [5] and alkaloid [6][7][8][9][10] natural products. These syntheses contain key steps that exploit the 100 % stereoselectivity [11] of reactions of the organometallic electrophiles.…”

“…These syntheses contain key steps that exploit the 100 % stereoselectivity [11] of reactions of the organometallic electrophiles. Our own work has concentrated on alkenyl-, [12] alkynyl- [13] and aryl- [8][9][10] substituted structures in which the activation provided by the metal is employed both in the construction and utilization of the electrophilic carbonyliron complexes. In the aryl series, we have developed a versatile approach that employs the twelve-carbon arylcyclohexadienyl component as a "C 12 building block", [14] which can correspond to the central portion of many alkaloid targets.…”