Catalytic, Asymmetric Halofunctionalization of Alkenes—A Critical Perspective

Abstract

Despite the fact that halogenation of alkenes has been known for centuries, enantioselective variants of this reaction have only recently been developed. In the past three years, catalytic enantioselective versions of halofunctionalizations with the four common halogens have appeared and although important breakthroughs, they represent just the very beginnings of a nascent field. This Minireview provides a critical analysis of the challenges that accompany the development of general and highly enantioselective halofunctionalization reactions. Moreover, the focus herein, diverges from previous reviews of the field by identifying the various modes of catalysis and the different strategies implemented for asymmetric induction.

Enantioselective, Catalytic Fluorolactonization Reactions with a Nucleophilic Fluoride Source

“…2a,3 Fluorofunctionalization of alkenes using F + sources is another powerful approach to the enantioselective synthesis of fluorine-containing chiral compounds that allows for the synthesis of highly functionalized products from simple olefin-containing starting materials. 4,5 In reported efforts directed toward enantioselective fluorolactonization reactions, electrophilic fluorinating reagents have been shown to afford γ-butyrolactone products with exocyclic fluoromethyl substituents in moderate-to-high enantioselectivity (Scheme 1, top). 6 We hypothesized that a hypervalent iodine catalysis of a nucleophilic fluorination pathway (“F − ”) could provide a complementary approach to regioisomeric fluorolactone products containing a C–F stereogenic center (Scheme 1, bottom), in a manner analogous to that observed in recently described enantioselective acetoxylactonization reactions.…”

Hypervalent Iodine Reagents as Powerful Electrophiles

“…33 An exhaustive range of enantiopure iodine-containing tartaric esters, alkaloids, and indane derivatives were prepared in excellent yields via coupling of the readily available iodocarboxylic acids. These catalysts failed to show any improvement in the selectivity of the oxytosylation reaction, and they demonstrated low levels of enantiocontrol in the related lactonization of 5-oxo-5-phenylpentanoic acid (17) to give lactone 18 (Scheme 7). 34 Ongoing interest in these catalytic transformations has highlighted the scope of the oxidants that can be employed.…”

Enantioselective Desymmetrization of Methylenedianilines via Enzyme-Catalyzed Remote Halogenation

“…3 The broad utility of halogenated compounds has driven extensive efforts to develop improved halogenation methods. 4–6 Enzymatic halogenation has recently emerged as a promising tool for installing halogen substituents due to the high selectivity, mild conditions, and environmentally benign reagents associated with halogenase catalysis. 7 …”