Helicenes with Embedded Phosphole Units in Enantioselective Gold Catalysis

Abstract

This paper discloses the first uses of phosphahelicenes as chiral ligands in transition-metal catalysis. Unlike all known helical phosphines used so far in catalysis, the phosphorus function of phosphahelicenes is embedded in the helical structure itself. This crucial structural feature originates unprecedented catalytic behaviors and efficiency. An appropriate design and fine tuning allowed both high catalytic activity and good enantiomeric excesses to be attained in the gold promoted cycloisomerizations of N-tethered 1,6-enynes and dien-ynes.

Helicene-Based Chiral Auxiliaries and Chirogenesis

“…A key synthetic step includes the diastereoselective photochemical cyclization reaction of a suitable (S P or R P ) enantiopure phosphole-bearing stilbene derivative 73. The resulting regioisomeric [6]helicene phosphine oxide 74 and phospha [7]helicene 75 were chromatographically separated with 32% and 28% yield, respectively [56] (Scheme 11). Another approach adopted was to design a helicene with the fused phosphole heterocyclic unit at one of the terminal rings where the phosphorus atom has an additional point chirality, denoted as SP or RP.…”

“…In endo-76, the gold atom occupies the internal chiral cavity space, approaching towards the opposite terminal ring, whereas in exo-77, the gold atom is situated at the external face, being away from the helical moiety. Thus, chromatographically separated endo-76 effectively catalyzes the enantioselective cycloisomerization of N-tethered 1,6-enyne 78 to give bicyclo[4.1.0]heptane 79 with 95% yield and 81% ee, whilst exo-77 remained almost inactive [56] (Scheme 12). Meanwhile, various phosphole-containing ligands were also prepared and screened in similar reactions with success [8,9,57].…”

“…Although this topic is not directly related to the category of helicene applications, it is an important background for the whole helicene chemistry; hence, a brief description should be included as a special section. The major methods of obtaining enantiopure helicenes from a racemic mixture are based on optical resolution by chiral HPLC [60,77,78,83,101], diastereomeric salt formation [51,60,76] (for representative resolving agents, see Figure 22), chromatographic separation of diastereomers [52,56,74], and enzymatic-based approaches [97]. …”

“…Particularly, it was observed that in 19 examples of helicenes studied, (M,S)-diastereomers were less polar, whilst (P,S)-diastereomers were more polar, hence eluting as the first and second fractions, correspondingly, upon the chromatographic separation on silica gel [107]. Another resolving agent, which is also frequently employed for optical resolution, is an l-menthyl derivative [4,56]. This approach has a distinct advantage of attaching and detaching a chiral auxiliary before and after the diastereomeric separation, making the whole procedure recyclable and highly efficient.…”

Enantioselective Gold-Catalyzed Synthesis of Heterocyclic Compounds

“…Substituted tetrahydropyridines and dihydropyrans were obtained with up to 98% ee. A creative strategy for enantioenriched tetrahydropyridines via enyne cycloisomerization was outlined by Voituriez et al, through the use of a helically chiral gold phosphine catalyst as shown in Scheme 25 [105]. A related class of ligands, phosphathiahelicenes, was also used for this transformation, allowing for even higher enantioselectivities with some substrates [106].…”