Nickel‐Catalyzed Construction of Chiral 1‐[6]Helicenols and Application in the Synthesis of [6]Helicene‐Based Phosphinite Ligands

Abstract

Two 1‐[6]helicenol derivatives were synthesized by Ni‐catalyzed [2+2+2] cycloaddition on a multigram scale. Both enantiomers of the 1‐[6]helicenols could be efficiently prepared by simple optical resolution. As a synthetic application of helically chiral 1‐[6]helicenols, a novel class of [6]helicene‐based phosphinites was developed; these compounds represent the first examples of helically chiral phosphinite ligands. Up to 90 % ee was obtained for the Pd‐catalyzed asymmetric allylic alkylation reaction.

Helicene-Based Chiral Auxiliaries and Chirogenesis

“…Similar types of C1 position substituted phosphinite ligands, helicenoid 53 [52] and helicene 54 [52] (Figure 9), were also prepared and successfully explored for the Pd-catalyzed asymmetric allylic alkylation between 50 and 51 (see Scheme 5). In both cases, the high yields and ee of 52 were obtained as with 53 (96%, 90% ee) and with 54 (97%, 99% ee) [52]. It is of note that this kinetic resolution reaction using helicene ligand 55 [53] was firstly reported in 2000 with 100% conversion and 81% ee ( Figure 9).…”

“…Thus, one can see that all phosphine (43, 44) and phosphinite (53, 54) ligands prepared later, possess only a mono phosphorus atom and are suitable for application as monodentate ligands in this reaction. Similar types of C1 position substituted phosphinite ligands, helicenoid 53 [52] and helicene 54 [52] (Figure 9), were also prepared and successfully explored for the Pd-catalyzed asymmetric allylic alkylation between 50 and 51 (see Scheme 5). In both cases, the high yields and ee of 52 were obtained as with 53 (96%, 90% ee) and with 54 (97%, 99% ee) [52].…”

“…Further, the separated diastereomers were hydrolyzed with alkali to quantitatively produce the enantiomer 60, which, on subsequent reaction with chlorodiphenylphosphine in the presence of sodium hydride, resulted in the tetrahydro phosphinite ligand, (P)-53. For 54, an additional step of dehydrogenation using triphenylmethylium tetrafluoroborate (Ph3CBF4) was required to obtain the diastereomer 61 (92%), which upon hydrolysis gave [6]helicen-1-ol 62, which was finally converted to phosphinite 54 with 74% yield (Scheme 7) [52]. Inspired by the difference in the catalytic performance of 43 (94% ee) and 44 (71% ee) (Scheme 6) in Pd-catalyzed asymmetric allylic alkylation, the same group also applied these ligands in other Pd- The corresponding enantiopure 53 and 54 were synthesized using the Ni-catalyzed [2 + 2 + 2] cycloaddition reaction of alkyne 56 to give 57 (97%), and the subsequent demethylation and esterification as (1S)-camphanate to yield the corresponding diastereomers, 58 and 59.…”

“…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]. …”

“…In the case of functionalized helicenecontaining phenolic groups at the terminal ring, (1S)-camphanic chloride acts as the best resolving agent for chromatographically separable diastereomers obtained. Furthermore, their absolute configuration determination was carried out by the 2D ROESY NMR technique [52,74,107]. 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].…”