Diamines chiral auxiliary

Syntheses and use of vicinal diamines with one or two N atoms included in heterocycle as chiral auxiliaries 98AG(E)2580. 

The highest ee s reported to date for the addition of achiral organometallic reagents in the presence of aprotic chiral additives were observed with the C2-symmetric diamines 10, 11 and 12 (Table 25)13 — 15. Enantioselectivities as high as 89% ee were observed with chiral auxiliary 1012. Addition of phenyllithium to pentanal proceeds with lower enantioselection that the analogous addition of butyllithium to benzaldehydeu. Generally, the enantioselcctivity in-... 

When a mixture of aldehydes and (Z)-l-ethylthio-l-trimethylsilyloxy-l-propene is added slowly to a solution of tin(Il) triflate and 10-20 mol% of the chiral diamine 4 in acetonitrile, /1-silyloxy thioesters 5 are obtained in high simple diastereoselection and induced stereoselectivity. Thus, the chiral auxiliary reagent can be used in substoichiometric amount. A rationale is given by the catalytic cycle shown below, whereby the chiral tin(II) catalyst 6 is liberated once the complex 7 has formed33. 

This report prompted further study of asymmetric dihydroxylation, and higher enantioselect-ivity has been realized with various C2- or quasi-C2-symmetric diamines as the chiral auxiliaries.168-174 One example reported by Tomioka and Koga is shown in Scheme 43.170 Although the reaction is highly enantioselective, it needs the use of stoichiometric 0s04 and chiral diamine, because the diamine coordinates Osvl ion strongly and retards its reoxidation to Osvm ion. 

In catalytic enantioselective Diels-Alder reactions, Mg11 catalysts bearing chiral auxiliaries, such as chiral bidentate ligands containing oxazoline moieties,27-29 chiral diamines,30 and... 

Since Sharpless discovery of asymmetric dihydroxylation reactions of al-kenes mediated by osmium tetroxide-cinchona alkaloid complexes, continuous efforts have been made to improve the reaction. It has been accepted that the tighter binding of the ligand with osmium tetroxide will result in better stability for the complex and improved ee in the products, and a number of chiral auxiliaries have been examined in this effort. Table 4 11 (below) lists the chiral auxiliaries thus far used in asymmetric dihydroxylation of alkenes. In most cases, diamine auxiliaries provide moderate to good results (up to 90% ee). 

In summary, the reaction of osmium tetroxide with alkenes is a reliable and selective transformation. Chiral diamines and cinchona alkakoid are most frequently used as chiral auxiliaries. Complexes derived from osmium tetroxide with diamines do not undergo catalytic turnover, whereas dihydroquinidine and dihydroquinine derivatives have been found to be very effective catalysts for the oxidation of a variety of alkenes. OsC>4 can be used catalytically in the presence of a secondary oxygen donor (e.g., H202, TBHP, A -methylmorpholine-/V-oxide, sodium periodate, 02, sodium hypochlorite, potassium ferricyanide). Furthermore, a remarkable rate enhancement occurs with the addition of a nucleophilic ligand such as pyridine or a tertiary amine. Table 4-11 lists the preferred chiral ligands for the dihydroxylation of a variety of olefins.61 Table 4-12 lists the recommended ligands for each class of olefins. 

A synthesis of novel chiral phosphine oxide aminal 113 has been developed by reacting phosphine oxide aldehyde 111 with diamine 112. The condensation gave a single diastereomer of the phosphine oxide aminal in 65% yield. This compound can be used as chiral auxiliary in asymmetric synthesis (Equation 15) <1996TA3431, 1996TL3051, 1996TL7465>. 

One major advantage of chiral auxiliary reagents over chiral a-substituted reagents is the fact that the chiral diol or diamine unit is not modified in the bond-making process and is thus potentially recyclable. The preparation of enan-tiomerically pure a-substituted reagents requires a stereoinductive transformation... 

The diamine (99) was applied 117) to the synthesis of chiral a-hydroxyaldehydes. Thus, treatment of the aminal (100), prepared from the chiral diamine (99) and phenylglyoxal, with the Grignard reagent affords the hydroxyaminal, which in turn was hydrolyzed to yield a-alkyl-a-hydroxyphenylacetaldehyde (101). The chiral auxiliary was recovered ll7). 

Extensive optimization studies identified highly electron-deficient 2,4-dinitrobenzyl-substituted aziridines as the most reactive substrates, chromium as the metal of choice, and indanol-derived Schiff bases as the most effective ligands. In this ring-opening process, catalyst 61 provided the highest selectivities. Using these optimized conditions, a variety of aziridines were selectively opened in a very efficient manner (Scheme 17.21).51 This reaction can provide an easy access to C2-symmetric 1,2-diamines, a valuable class of chiral auxiliaries, and even to less accessible non-C2-symmetric 1,2-diamines because of the differentially protected amines of the ring-opened products. 

Another important source of chiral auxiliaries for the synthesis of optically active phosphorus derivates are the C2 symmetric diamines such as 1,2-diaminocyclohex-anes. In 1994, Hanessian and co-workers described the use of A,/V -dimethyl-(R,R)-1,2-diaminocyclohexane 93 as a chiral auxiliary in the synthesis of optically pure or enantiomerically enriched a-alkyl a-amino phosphonic acids [49], Starting from easily accessible optically pure diamine 93, they synthesized in good yield (75 %) enantiomerically pure (R,R)-ethylphosphonamide 94 by condensation with ethyl phosphonic dichloride in benzene in the presence of triethylamine (Scheme 43). 

The excellent enantioselectivity and wide scope of the CBS reduction have motivated researchers to make new chiral auxiliaries [3]. Figure 1 depicts examples of in situ prepared and preformed catalyst systems reported since 1997. Most of these amino-alcohol-derived catalysts were used for the reduction of a-halogenated ketones and/or for the double reduction of diketones [16-28]. Sulfonamides [29,30], phosphinamides [31], phosphoramides [32], and amine oxides [33] derived from chiral amino alcohols were also applied. The reduction of aromatic ketones with a chiral 1,2-diamine [34] and an a-hydroxythiol [35] gave good optical yields. Acetophenone was reduced with borane-THF in the presence of a chiral phosphoramidite with an optical yield of 96% [36]. 

Several methods promoted by a stoichiometric amount of chiral Lewis acid 38 [51] or chiral Lewis bases 39 [52, 53] and 40 [53] have been developed for enantioselective indium-mediated allylation of aldehydes and ketones by the Loh group. A combination of a chiral trimethylsilyl ether derived from norpseu-doephedrine and allyltrimethylsilane is also convenient for synthesis of enan-tiopure homoallylic alcohols from ketones [54,55]. Asymmetric carbonyl addition by chirally modified allylic metal reagents, to which chiral auxiliaries are covalently bonded, is also an efficient method to obtain enantiomerically enriched homoallylic alcohols and various excellent chiral allylating agents have been developed for example, (lS,2S)-pseudoephedrine- and (lF,2F)-cyclohex-ane-1,2-diamine-derived allylsilanes [56], polymer-supported chiral allylboron reagents [57], and a bisoxazoline-modified chiral allylzinc reagent [58]. An al-lyl transfer reaction from a chiral crotyl donor opened a way to highly enantioselective and a-selective crotylation of aldehydes [59-62]. Enzymatic routes to enantioselective allylation of carbonyl compounds have still not appeared. 

The bis(dioxolanyl)oxazolidinone 33 has been prepared from D-mannitol and evaluated as a chiral auxiliary <02MT749> and the diamine 34 has been examined as a ligand for rhodium catalysed asymmetric hydrogenation of diethyl itaconate <02JOU104>. Deracemisation of 2-benzylcyclohexanone by formation of an inclusion complex with the TADDOL compound 35 has been described and the mechanism clarified by X-ray structure determination of the complex <02T3401>. A production process for the bis(phosphine oxide) 36 has been patented <02USP6472539>. 

The iodocyclization of acyclic unsaturated isoureas containing (S )-phenylethylamine as the chiral auxiliary gave chiral cyclic isoureas, which are masked 1,2-diamines. Starting from (S)-phenyl-ethylamine, the corresponding cyanamide was easily obtained, which was then converted, after allylation, to the corresponding isourea. The iodocyclization of the isourea derived from (S)-phenylethylamine afforded an equimolar diastereomeric mixture of 4,5-dihydroimidazoles 4 in 90% yield, which were easily separated by chromatography167. 

Chiral C2-symmetric vicinal diamines have emerged as powerful tools for the synthesis of enantiomerically pure compounds and are now commonly used as chiral auxiliaries or ligands for a wide array of asymmetric chemical transformations, with efficiencies comparable to those obtained with the closely related... 

Chiral Auxiliary. Chiral 1,2-diamines have often been used as chiral auxiliaries in various carbon-carbon bond-forming reactions. The reaction of a diamine with an aldehyde gives a chiral aminal which can undergo stereoselective reactions. This was applied in the synthesis of enantiomerically pure a-hydrazino aldehydes by stereoselective addition of carbon nucleophiles onto the aminal of glyoxal monohydrazone (eqs 2 and 3). In this reaction, the use of 1,2-diaminocyclohexane gave lower diastereomeric excesses than with the related 1,2-diphenyl ethylenediamine. 

Deprotection of the chiral auxiliary groups is performed using ammonium formate, acetic acid, and palladium hydroxide in refluxing ethanol (eq 2). This sequence gives, after purification by distillation, the free optically pure (/J,/J)-diamine 3. ... 

Utility. Many asymmetric syntheses have been developed using vicinal diamines as the source of chirality. The major interest lies in their use as precursors for the synthesis of a broad family of bidentate ligands. Many reactions have also been described using the N-alkyl derivatives of these diamines as chiral auxiliaries and protecting groups of aldehydes. Most of these applications generally use the framework of l,2-diphenyl-l,2-diaminoethane (7) or 1,2-diaminocyclohexane (8), whose preparations have been fully described. ... 

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