Enantioselective Iron-Catalyzed Cross-[4+4]-Cycloaddition of 1,3-Dienes Provides Chiral Cyclooctadienes

Abstract

Chiral cyclooctadienes are a frequently occurring scaffold in natural products and specialty chemicals, and are used as ligands in asymmetric catalysis. Accessing substituted cyclooctadienes in an efficient asymmetric fashion has been notoriously challenging. We report an iron-catalyzed enantioselective cross-[4+4]-cycloaddition of 1,3-dienes to form substituted cyclooctadienes under very mild conditions. A highly tailored chiral α-diimine iron complex is key for the success of the transformation providing a balanced performance between reactivity, excellent cross-selectivity and very high enantioselectivity. Steric maps of the complexes help accounting for the observed selectivity. The developed method allows rapid and atom-economic access to novel differently functionalized cyclooctadienes in very high yields and enantioselectivities.

Crossed Regio‐ and Enantioselective Iron‐Catalyzed [4+2]‐Cycloadditions of Unactivated Dienes

“…For instance, using the same set of alkyl substituted dienes ( 1 a , 1 m paired with 2 i ), catalyst Fe7 selectively induces the cross‐[4+2]‐cycloaddition yielding vinyl‐cyclohexenes 3 ai and 3 mi . In contrast, cyclooctadienes 4 ai and 4 mi were exclusively formed using Fe10 as the catalyst [28] …”

“…We have recently reported a chiral α‐diimine iron catalyst class enabling the enantioselective cross‐[4+4]‐cycloaddition of alkyl‐substituted 1,3‐dienes to cyclooctadienes [28] . Along the same lines, Chirik reported exclusive access to aryl‐substituted [4+4]‐cycloadducts with a pyridine‐imine (PI) iron catalyst [27] .…”

“…The application of Earth‐abundant metals such as iron [20–22] in catalysis is highly desirable due to their high availability, low price and low toxicity. Diimine iron‐complexes are particularly attractive due to their ability to catalyze a variety of reactions, such as olefin polymerization, [23] hydrofunctionalization [24] and cycloadditions [25–28] . The diimine ligand precursors are easily accessible and modular in nature, allowing facile tuning of the steric and electronic properties of the corresponding iron complexes.…”

Crossed Regio‐ and Enantioselective Iron‐Catalyzed [4+2]‐Cycloadditions of Unactivated Dienes

“…In contrast, cyclooctadienes 4 ai and 4 mi were exclusively formed using Fe10 as the catalyst. [28] To rationalize the effects of the catalyst on the chemoselectivity of the transformation, a working model for the mechanism could be formulated by combining previous findings from Chirik [26,27,36] and Lin [37] To gauge the influence of the (E/Z)-geometry of the linear diene 2 on the cycloaddition outcome, we independently reacted (E)-2 f and (Z)-2 f with 1 a in the presence of Fe5 (Scheme 5 A). Irrespectively of the starting double bond configuration, cyclohexene 3 af bearing an (E)-exocyclic double bond was obtained in both cases as the sole geometrical isomer in excellent yield.…”

“…We have recently reported a chiral a-diimine iron catalyst class enabling the enantioselective cross-[4+4]-cycloaddition of alkyl-substituted 1,3-dienes to cyclooctadienes. [28] Along the same lines, Chirik reported exclusive access to arylsubstituted [4+4]-cycloadducts with a pyridine-imine (PI) iron catalyst. [27] In a follow-up, we were wondering if selective formation of cross-[4+2]-cycloadduct 3 over the competing [4+4]-product as well as linear isomers and oligomers could be triggered by catalyst/ ligand tuning.…”