Asymmetric imidation

New synthetic efforts generated a few structural derivatives of Lilm with longer perfluorinated alkyls such as LiBeti and a lithium salt of an asymmetric imide anion, and the stability of A1 in the electrolytes based on these salts was found to be much improved when compared with those in electrolytes based on Lilm and LiTf.i i s... 

Large anion size was also found to favor A1 stabilization, since the 1710 cm signature did not appear till a potential higher than 5.0 V was reached for the new, asymmetric imide. Unlike the interpretation of Krause et al., Kanamura et al. attributed its inertness to the well-distributed negative charge and the lower probability of these anions forming an ion pair with AP+. ... 

Asymmetric imidations of aryl alkyl sulfides with [(tosylimino)iodo]ben-zene, catalyzed by various chiral (salen)manganese(III) complexes, have been investigated in some detail [31,32]. The influence of catalyst structure, solvent, temperature, 3°-amine AT-oxides, and the presence of molecular sieves on product yields and the enantioselectivity of imidation with 17 was evaluated. Enan-tioselectivities as high as 90 % ee and 97 % ee with methyl 2-nitrophenyl sulfide and methyl 2,4-dinitrophenyl sulfide, respectively, were achieved. 

Enantioselective conversions of aryl benzyl selenides to N-tosylselenimides 28 with [(tosylimino)iodo]benzene, cuprous triflate, and the chiral bis(oxazo-line) 22 have recently been demonstrated (Scheme 16) [37,38]. Because benzyl phenyl selenide undergoes uncatalyzed imidation with Phi = NTs in acetonitrile (46 % yield) or dichloromethane (trace yield), toluene was selected as the solvent for the asymmetric imidation reactions. Furthermore, in order to avoid racem-ization of 28 by moisture, molecular sieves were added to the reaction medium. 

Kinetic resolution of secondary alcohols is performed by asymmetric oxidation using an optically active (nitroso)(salen)ruthenium(II) chloride 12 (Eq. 3.14) [48]. The ruthenium catalyst 12 is also effective for asymmetric imidation of alkyl aryl sulfide [48c]. 

Catalytic Nitrene Transfer to Heteroatoms. The experimental procedure described above for the copper-catalyzed aziridination of olefins can be applied to the imidation of sulfides, where CuOTf in conjunction with PhI=NTs mediates the formation of siilfimides in good yields (eq 95). Spontaneous [2,3] sigma-tropic rearrangements occur in the case of allylic sulfides. Chiral bis(oxazoline)-CuOTf complexes catalyze both reactions with acceptable enantioselectivities (eq 96). Chloratnine-T is also a suitable but less efficient nitrene precursor. Selenides undergo the same catalytic asymmetric imidation to afford selenimides albeit with lower yields and enantioselectivities. ... 

Asymmetric reactions using chiral memory derived from asymmetric imides... 

Industrial Synthetic Improvements. One significant modification of the Stembach process is the result of work by Sumitomo chemists in 1975, in which the optical resolution—reduction sequence is replaced with a more efficient asymmetric conversion of the meso-cyc. 02Lcid (13) to the optically pure i7-lactone (17) (Fig. 3) (25). The cycloacid is reacted with the optically active dihydroxyamine [2964-48-9] (23) to quantitatively yield the chiral imide [85317-83-5] (24). Diastereoselective reduction of the pro-R-carbonyl using sodium borohydride affords the optically pure hydroxyamide [85317-84-6] (25) after recrystaUization. Acid hydrolysis of the amide then yields the desired i7-lactone (17). A similar approach uses chiral alcohols to form diastereomic half-esters stereoselectivity. These are reduced and direedy converted to i7-lactone (26). In both approaches, the desired diastereomeric half-amide or half-ester is formed in excess, thus avoiding the cosdy resolution step required in the Stembach synthesis. 

A key step in the synthesis of the spiroketal subunit is the convergent union of intermediates 8 and 9 through an Evans asymmetric aldol reaction (see Scheme 2). Coupling of aldehyde 9 with the boron enolate derived from imide 8 through an asymmetric aldol condensation is followed by transamination with an excess of aluminum amide reagent to afford intermediate 38 in an overall yield of 85 % (see Scheme 7). During the course of the asymmetric aldol condensation... 

The synthesis of the polyol glycoside subunit 7 commences with an asymmetric aldol condensation between the boron enolate derived from imide 21 and a-(benzyloxy)acetaldehyde (24) to give syn adduct 39 in 87 % yield and in greater than 99 % diastereomeric purity (see Scheme 8a). Treatment of the Weinreb amide,20 derived in one step through transamination of 39, with 2-lithiopropene furnishes enone 23 in an overall yield of 92 %. To accomplish the formation of the syn 1,3-diol, enone 23 is reduced in a chemo- and... 

Inherent in the reduction of asymmetrically substituted cyclic imides is the problem of regiose-lectivity. Imides, in which one carbonyl group is part of a (thio)carbamate or urea function, usually show complete chemoselectivity for reduction of the other carbonyl group, indicated with an arrow. 

Diisobutylaluminum hydride (DIBAL-H) can also be used for partial reduction of cyclic imides37. Although less convenient than sodium borohydride, an important synthetic aspect is the fact that in the reduction of asymmetrically substituted imides, diisobutylaluminum hydride and sodium borohydride may show opposite regioselectivity38,39. 

Oxazol-4-ones 132 have been prepared by Trost and co-workers via a microwave-assisted cyclocondensation of bromo imides in the presence of NaF [86]. These products where then employed for a Mo-catalyzed asymmetric synthesis of Q -hydroxycarboxylic acid derivatives 134 (Scheme 47). 

Kang J, Yew KH, Kim TH, Choi DH (2002) Preparation of bis [palladacycles] and application to asymmetric aza-Claisen rearrangement of allylic imidates. Tetrahedron Lett 43 9509-9512... 

Anderson CE, Donde Y, Douglas CJ, Overman LE (2005) Catalytic asymmetric synthesis of chiral allylic amines. Evaluation of ferrocenyloxazoline palladacycle catalysts and imidate motifs. J Org Chem 70 648-657... 

In 1999, this methodology was applied to the synthesis of unnatural biologically active ( + )-5-epi-nojirimycin-5-lactam, a potent and selective glycosidase inhibitor.The key step of this synthesis was the asymmetric reduction of a cyclic triacetyloxy meso imide under the same conditions to those described above, which resulted in the formation of the corresponding hydroxy 5-lactam in good yield and enantioselectivity of 85% ee (Scheme 10.59). 

A simple two-step synthesis of 5H-alkyl-2-phenyloxazol-4-ones has been reported by Trost and coworkers (Scheme 6.209) [377]. a-Bromo acid halides were condensed with benzamide in the presence of pyridine base at 60 °C to form the corresponding imides. Microwave irradiation of the imide intermediates in N,N-dimethylacetamide (DMA) containing sodium fluoride at 180 °C for 10 min provided the desired 5H-alkyl-2-phenyloxazol-4-ones (oxalactims) in yields of 44—82%. This class of heterocycles served as excellent precursors for the asymmetric synthesis of a-hydroxycar-boxylic acid derivatives [377]. 

Imide Systems. Imide compounds 22 and 23, or Evans reagents, derived from the corresponding oxazolidines are chiral auxiliaries for effective asymmetric alkylation or aldol condensation and have been widely used in the synthesis of a variety of substances. 

This imide system can also be used for the asymmetric synthesis of optically pure a,a-disubstituted amino aldehydes, which can be used in many synthetic applications.31 These optically active a-amino aldehydes were originally obtained from naturally occurring amino acids, which limited their availability. Thus, Wenglowsky and Hegedus32 reported a more practical route to a-amino aldehydes via an oxazolidinone method. As shown in Scheme 2 20, chiral diphenyl oxazolidinone 26 is first converted to allylic oxazolidinone 27 subsequent ozonolysis and imine formation lead to compound 28, which is ready for the a-alkylation using the oxazolidinone method. The results are shown in Table 2-6. 

Asymmetric Diels-Alder reactions have been carried out to investigate the efficacy of anilide 44 and imide 45 as dienophiles. In the presence of iodine, the asymmetric Diels-Alder reaction of anilide (+)-44 shows a remarkable improvement in both reactivity and stereoselectivity (Table 5-1). Therefore, it is believed that, in the presence of I2, Diels-Alder reactions of A -al I yl ic enamides take place through an activating process involving the formation of a cationic iodocyclization intermediate. 

This preparation illustrates a general method for the synthesis of N-methylalkylamines. The submitters have used it to prepare N-methylbutylamine (Note 4) and N-methylallylamine, and the checkers have used it to prepare N-methylisopropylamine (80%), N-methylisobutylamine (67%), N-methyl-fert-butylamine (52%), and N-methyl-2-methoxyethylamine (55%). Secondary amines are useful as starting materials for the synthesis of 1,1-disubsti-tuted hydrazines and asymmetric amine imides. 

Asymmetric Diels-Alder reactions. Unlike methyl crotonate, which is a weak dienophile, chiral (E)-crotonyl oxazolidinones when activated by a dialkylaluminum chloride (1 equiv.) are highly reactive and diastereoselective dienophiles. For this purpose, the unsaturated imides formed from oxazolidinones (Xp) derived from (S)-phenylalanol show consistently higher diastereoselectivity than those derived from (S)-valinol or (IS, 2R)-norephedrine. The effect of the phenyl group is attributed in part at least to an electronic interaction of the aromatic ring. The reactions of the unsaturated imide 1 shown in equation (I) are typical of reactions of unsaturated N-acyloxazolidinones with cyclic and acyclic dienes. All the Diels-Alder reactions show almost complete endo-selectivity and high diastereoselectivity. Oxazolidinones are useful chiral auxiliaries for intramolecular Diels-Alder... 

It is significant to note that the sense of asymmetric induction noted for amide enolates 157 and 158 is the same as that found for the boryl enolates derived from the chiral oxazolidone imides 146 and 145, respectively (cf. Scheme 22). The arguments presented... 

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