Letter Cite This: Org. Lett. 2017, 19, 5709-5712
pubs.acs.org/OrgLett
Intramolecular Direct C−H Arylation via a Metallocenic Radical Pathway: Stereospecific Approach to Planar-Chiral Ferrocenes Yang Liu,‡ Jiancong Xu,‡ Jinling Zhang, Xiaohua Xu,* and Zhong Jin* State Key Laboratory and Institute Elementoorganic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China S Supporting Information *
ABSTRACT: Transition metal-free synthesis of planar-chiral 1,2-fused ferrocenes via intramolecular direct C−H bond arylation was achieved. The C−H arylation reactions promoted by a catalytic amount of 1,10-phenanthroline highlighted a unique planar-chiral metallocenic radical intermediate, generated from iodoferrocenes via a single-electron transfer process.
P
tion for synthesis of planar-chiral benzosiloloferrocenes has also been developed by the groups of Shibata,8 He,9 and Murai and Takai,10 independently. In addition, gold- or platinum-catalyzed cycloisomerization of ortho-alkynylaryl ferrocenes was demonstrated to afford planar-chiral naphthene-fused ferrocenes with high enantioselectivity.11 Despite this tremendous progress, development of alternative methodologies for asymmetric synthesis of this class of organometallics still remains necessary given the significant importance of planar-chiral ferrocenes. Since the first report on transition metal-free coupling of haloarenes with N-heterocycles was published by Itami and co-workers in 2008,12 this class of cross-coupling reaction between aryl halides and unactivated arenes has received extensive interest in light of its transition metal-free merit.13 In the presence of an organic strong base, typically KOtBu, inter- and intramolecular cross-coupling of aryl halides with arenes could be promoted by various organic molecules, such as 1,10-phenanthrolines, 1,2-diamines, and others.14,15 Encouraged by the aforementioned success, we envisioned that planar-chiral 1,2-fused ferrocenes could be synthesized via intramolecular direct C−H arylation under transition metal-free conditions. We herein report a stereospecific approach to planar-chiral 1,2-fused ferrocenes via intramolecular direct C−H bond arylation involving a chiral metallocenic radical pathway (Scheme 1c). At the outset, chiral ferrocenocarboxamide (Sp)-2a (96:4 er), easily prepared from ferrocenocarboxylic acid according to the previous procedure,16 was employed as a model reactant and various reaction conditions were optimized (Table 1) (see the Supporting Information for the details). Among the alkali metal tert-butoxides, KOtBu was shown to be the optimal base (entries 1−3, Table 1). The efficacy of 1,10-phenanthrolines was greatly associated with their substitution patterns in the scaffold. A coupling reaction promoted by 1,10-phenanthroline (C1) gave the arylation product 3a in 92% yield, while with 2,9-dimethyl phenanthroline (C2) as an additive only a trace amount of
lanar-chiral ferrocenes are a class of intriguing organometallic molecules in the fields of organic synthesis, materials science, and medicinal chemistry.1 In particular, application of ligands based on planar-chiral ferrocene scaffolds in transition metal-catalyzed asymmetric synthesis have witnessed enormous progress over the past decades.2 Recently, planar-chiral 1,2-fused ferrocenes have proven also to be highly efficient chiral ligands and catalysts in asymmetric catalysis (Scheme 1a).3 However, to date, efficient approaches to these Scheme 1. Planar-Chiral Ferrocenes (a) and Approach to Planar-Chiral Ferrocenes via Intramolecular C−H Arylation (b and c)
planar-chiral 1,2-fused ferrocenes are rather rare. In 1997, Schmalz and co-workers accomplished a copper-catalyzed enantioselective insertion of carbenoids into a Cp−H bond of ferrocene giving the optically active ferrocene-fused cyclic ketones.4 Very recently, intensive efforts on transition metalcatalyzed direct C−H functionalization for synthesis of planarchiral ferrocene-fused derivatives have been made (Scheme 1b). The research groups of You,5 Gu,6 and Liu and Zhao7 have independently reported a palladium-catalyzed enantioselective intramolecular direct C−H arylation with halobenzenes leading to planar-chiral indenone- and quinolinone-fused ferrocenes. A rhodium-catalyzed enantioselective intramolecular C−H silyla© 2017 American Chemical Society
Received: September 24, 2017 Published: October 5, 2017 5709
DOI: 10.1021/acs.orglett.7b02995 Org. Lett. 2017, 19, 5709−5712
Letter
Organic Letters
anion was likely to be disassociated with the CpFe+ ion. When the resulting cyclopentadienyl radical anion turn upside down and recoordinated to the CpFe+ ion, racemization occurred and an enantiomer of the original chiral ferrocenyl radical was obtained. The polar solvent, for example, THF and DME, were reasoned to be beneficial to the solvolytic dissociation of the CpFe+ cation and preferred to cause racemization. With the optimal conditions in hand, the generality of the protocol with a wide array of anilines was then examined. As shown in Scheme 2, in all cases planar-chiral ferrocene-fused
Table 1. Optimization of Reaction Conditions
Scheme 2. Intramolecular Direct C−H Arylation with PlanarChiral Iodoferrocenesa entry
base (equiv)
additive
solvent
yield (%)a
erb
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
LiOtBu (3.0) NaOtBu (3.0) KOtBu (3.0) KOtBu (4.0) KOtBu (4.0) KOtBu (4.0) KOtBu (4.0) KOtBu (4.0) KOtBu (4.0) KOtBu (4.0) KOtBu (4.0) KOtBu (4.0) KOtBu (4.0) KOtBu (4.0) KOtBu (4.0) KOtBu (4.0) KOtBu (4.0) KOtBu (4.0) KOtBu (4.0) KOtBu (4.0)
C1 C1 C1 C1 C2 C3 C4 C5 C6 C7 C8 C9 C10 C1 C1 C1 C1 C1 C1 C1
THF THF THF THF THF THF THF THF THF THF THF THF THF DME dioxane benzene toluene m-xylene p-xylene mesitylene
