Absolute Asymmetric Synthesis of Enantiopure Organozinc Reagents, Followed by Highly Enantioselective Chlorination

Abstract

We report the absolute asymmetric synthesis (AAS) of indenylzinc reagents by using total spontaneous resolution followed by enantiospecific conversion into 1-chloroindene. The chiral complex [Zn(dcp)(ind)(tmeda)] (dcp = 2,6-dichlorophenoxy and tmeda = N,N,N',N'-tetramethylethylenediamine) (3) was prepared from the achiral starting materials indene, potassium, zinc chloride, TMEDA, and 2,6-dichlorophenol. The reagent resolved spontaneously on crystallization, and single crystals of 3 react with N-chlorosuccinimide in the presence of benzoquinone in 2-propanol to give 1-chloroindene in >98 % enantiomeric excess. It was found that (R)-3 gave (R)-1-chloroindene upon reaction, indicating an SE 2'-mechanism. Since bulk samples of 3 gave optically active product upon chlorination, total spontaneous resolution must have occurred. This demonstrates that enantiopure products can be obtained through the absolute asymmetric synthesis of organometallic reagents starting from achiral materials. The general absolute asymmetric synthesis (AAS) method offers easy access to both enantiomers and an almost limitless variation in the design of the product.

Viedma Ripening of Conglomerate Crystals of Achiral Molecules Monitored Using Solid-State Circular Dichroism

“…To our knowledge, there are only two reported examples where deracemization of conglomerate crystals was not achieved under Viedma ripening conditions: 3-hydroxy-3-phenylisoindolin-1-ones (type ii) 29 and a diindenylzinc organometallic complex (type ii). 30 Surprisingly, given the relative abundance of achiral molecular conglomerates, sodium chlorate, sodium bromate, and ethylenediammonium sulfate are the only three examples of this family shown to undergo Viedma ripening (Table 1, type i). These systems can be considered as the simplest, given that the molecules are inherently achiral in solution.…”

“…Furthermore, by merging an enantioselective interaction with this autocatalytic amplification process, the mirror symmetry breaking could be directed on the basis of the chirality of the additive (i.e., following the “rule of reversal” implemented under attrition conditions). , To date, there are 13 crystalline systems that undergo Viedma ripening that can be classified as having the following: (i) achirality in solution, (ii) a racemizing state in solution, or (iii) a reversible racemizing reaction in solution (Table ). To our knowledge, there are only two reported examples where deracemization of conglomerate crystals was not achieved under Viedma ripening conditions: 3-hydroxy-3-phenylisoindolin-1-ones (type ii) and a diindenylzinc organometallic complex (type ii) …”

Spontaneous Generation of Chirality in Simple Diaryl Ethers

“…The bulk will then be obtained in an optically active state, and total spontaneous resolution means that an excess (but not necessarily 100%) is obtained of one enantiomorph. Over the past years, we have studied total spontaneous resolution and absolute asymmetric synthesis of a variety of molecules, ranging from pure organic substances to organometallic reagents and coordination compounds . In this work we study four simple diaryl ethers, 3‐phenoxybenzaldehyde, 1 ; 1,3‐dimethyl‐2‐phenoxybenzene, 2 ; di(4‐diaminophenyl) ether, 3 ; and di( p ‐tolyl) ether, 4 (Scheme ), all of which spontaneously form chiral crystals.…”

Frozen Chirality of Tertiary Aromatic Amides: Access to Enantioenriched Tertiary α‐Amino Acid or Amino Alcohol without Chiral Reagent

“…In fact, it is well known that an achiral compound can spontaneously crystallize in enantiomorphous space groups (such as NaClO 3 or dibenzoylperoxide), or, very rarely, that a racemic compound can crystallize in a macroscopic chiral arrangement (such as racemic o ‐tyrosine) . These chiral crystals (organic or inorganic) are employed as either reactant or catalyst, and they are frequently used in the fields of photochemical cycloaddition or asymmetric autocatalysis . To avoid racemization in solution of the conformational chirality fixed in the crystal, the reactions are often performed in the solid state.…”