Catalytic Enantioselective Addition of Alkylzirconium Reagents to Aliphatic Aldehydes.

Jade Vaccari,Nicholas Carter,María José González-Soria,Beatriz Maciá

doi:10.3390/molecules26154471

Jade Vaccari, Nicholas Carter + Show 2 more

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https://doi.org/10.3390/molecules26154471

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Abstract

A catalytic methodology for the enantioselective addition of alkylzirconium reagents to aliphatic aldehydes is reported here. The versatile and readily accessible chiral Ph-BINMOL ligand, in the presence of Ti(OiPr)4 and a zinc salt, facilitates the reaction, which proceeds under mild conditions and is compatible with functionalized nucleophiles. The alkylzirconium reagents are conveniently generated in situ by hydrozirconation of alkenes with the Schwartz reagent. This work is a continuation of our previous work on aromatic aldehydes.

Highlights

Chiral aliphatic secondary alcohols—ubiquitousstructures in natural products—play a very important role in chemical communication among living organisms, serving as sex, aggregation, alarm and trail pheromones, attractants or repellents
The enantioselective synthesis of aliphatic alcohols has been recognized as a longterm interest in the chemistry community, and a wide variety of catalytic asymmetric methodologies [2,3] allow access to these relevant moieties in high enantiomeric excess, including reduction or hydrogenation of prochiral aliphatic ketones [4,5] and addition of alkyl organometallic reagents to aliphatic aldehydes [6,7]
The corresponding alkylzirconium reagent was prepared by treatment of 1-hexene (2a, 2.2 eq) with

Summary

Introduction

Chiral aliphatic secondary alcohols—ubiquitous (sub)structures in natural products—. play a very important role in chemical communication among living organisms, serving as sex, aggregation, alarm and trail pheromones, attractants or repellents. The enantioselective synthesis of aliphatic alcohols has been recognized as a longterm interest in the chemistry community, and a wide variety of catalytic asymmetric methodologies [2,3] allow access to these relevant moieties in high enantiomeric excess, including reduction or hydrogenation of prochiral aliphatic ketones [4,5] and addition of alkyl organometallic reagents to aliphatic aldehydes [6,7]. We report the enantioselective addition of alkylzirconium reagents to aliphatic aldehydes, using a chiral titanium-(Ph-BINMOL) complex as catalyst in the presence of a zinc salt, under industrially relevant reaction conditions. The in-situ preparation of the alkylzirconium nucleophile allows the synthesis of chiral secondary aliphatic alcohols bearing functional groups that are not compatible with other premade organometallic reagents. This work is an extension of our previous, recently published work [67], where only aromatic aldehydes were employed as substrates

Results and Discussion

Conclusions

Materials and Methods enced to