Amino acids chiral ylides

Hashimoto and co-workers (139) further looked at an intermolecular carbonyl ylide cycloaddition screening several different chiral rhodium catalysts. The Hashimoto group chose to study phthaloyl amino acid derivatives for enantiocon-trol of the cycloaddition reactions (Fig. 4.8). Using fluorinated or ethereal solvents with the phthaloyl catalysts gave ee ratios of 20-69%. 

The amino acid derived chiral oxazolidinone 188 is a very commonly used auxiliary in Diels-Alder and aldol reactions. However, its use in diastereoselective 1,3-dipolar cycloadditions is less widespread. It has, however, been used with nitrile oxides, nitrones, and azomethine ylides. In reactions of 188 (R = Bn, R =Me, R = Me) with nitrile oxides, up to 92% de have been obtained when the reaction was performed in the presence of 1 equiv of MgBr2 (303). In the absence of a metal salt, much lower selectivities were obtained. The same observation was made for reactions of 188 (R = Bn, R = H, R = Me) with cyclic nitrones in an early study by Murahashi et al. (277). In the presence of Znl2, endo/exo selectivity of 89 11 and up to 92% de was observed, whereas in the absence of additives, low selectivities resulted. In more recent studies, it has been shown for 188 (R =/-Pr, R = H, R =Me) that, in the presence of catalytic amounts of Mgl2-phenanthroline (10%) (16) or Yb(OTf)3(20%) (304), the reaction with acyclic nitrones proceeded with high yields and stereoselectivity. Once again, the presence of the metal salt was crucial for the reaction no reaction was observed in their absence. Various derivatives of 188 were used in reactions with an unsubstituted azomethine ylide (305). This reaction proceeded in the absence of metal salts with up to 60% de. The presence of metal salts led to decomposition of the azomethine ylide. 

The vast majority of organocatalytic reactions proceeds via covalent formation of the catalyst-substrate adduct to form an activated complex. Amine-based reactions are typical examples, in which amino acids, peptides, alkaloids and synthetic nitrogen-containing molecules are used as chiral catalysts. The main body of reactions includes reactions of the so-called generalized enamine cycle and charge accelerated reactions via the formation of iminium intermediates (see Chapters 2 and 3). Also, Morita-Baylis-Hillman reactions (see Chapter 5), carbene-mediated reactions (see Chapter 9), as well as asymmetric ylide reactions including epoxidation, cyclopropanation, and aziridination (see Chapter 10), and oxidation with the in situ generation of chiral dioxirane or oxaziridine catalysts (see Chapter 12), are typical examples. 

When azomethine ylides are generated by condensation of aldehydes with chiral a-amino acids, the stereogenic center of the latter is lost in the planar 1,3-dipole structure. To achieve diastereoselection in the addition to Ceo, an additional chiral element is therefore needed. An optically pure azomethine ylide was generated by reaction of (+)-2,3-0-isopropylidene-D-glyceraldehyde with... 

Other examples of stereoselective additions of sulfoxonium methylide (2) to chiral aldehydes are shown in equations (8), - (9) and (10). At present, no one model is able to account for all of these results. Equations (lOa) and (lOb) show the effect of a nitrogen protecting group on the stereoselectivity of addition of unstabilized ylide (1) to a-amino acid derived aldehydes. The major products of... 

Thermal decomposition of l,4-dihydro-2,3-benzoxathiin 3-oxides generates o-xylylenes which can be trapped by methyl 2-acetamidoacrylate yielding tetralin-based a-amino acids <04S558>. A phosphazene base [EtN=P(NMe2)2(N=P(NMe)2)3)] is used to generate the ylide from chiral oxathiane 74 in a two-step asymmetric synthesis of aziridines from tosylimines <04JOC1409>. 

Chiral induction in cycloaddition reactions of azomethine ylide has been achieved when the a-amino acid (233) reacts with isatin or benzthiophen derivatives (234 X = NH, NBu, S) and menthyl acrylate. The course of the reactions involves decarboxylative azomethine ylide formation followed by cycloaddition through an endo transition state ultimately affording the cycloadduct (61) (Table 9) in 67-82% diastereomeric excess <91TL5417>. 

Chiral cychc and acyclic allylsulfoxonium ylides are generated from sulfoxonium-substi-tuted y,8-unsaturated a-amino acids (method A) and 1-alkenylsulfoxonium salts (method B) upon treatment with DBU (1) [51] (Scheme 3.31). Their apphcation to the asymmetric aziridination of A-ferf-butylsulfonyl imine ester, generated either in situ (method A) or externally added (method B), affords the corresponding alkenylaziridinecarboxylate with medium to high diastereoselectivity and enantioselectivity. 

Reactions of chiral azomethine ylides usually derived from imines of a-amino acids have been achieved with electron-deficient alkenes and a, 3-unsaturated carboxylic acid derivatives furnishing pyrrolidines. 

The 1,3-dipolar cycloaddition reaction of non-stabilized azomethine ylides, derived from A-alkyl-cf-amino acids, with 3-nitro-2-trifluoro(trichloro)methyl-2//-chromenes produced l-benzopyrano[3,4-c]pyrrolidines in good yields." AgOAc-catalysed asymmetric 3 + 2-cycloaddition reactions of azomethine ylides with e-deficient alkenes yielded enr/o-adducts with up to 99% ee. New chiral ferrocenyl P,N-ligands possessing a benzoxazole ring as the Af-donor (35) are effective asymmetric catalysts... 

A-Sulfonylaldimines produced by condensation of SES-NFI2 with various aldehydes are converted into enantiomerically enriched aziridines upon reaction with certain sulfur ylides. The same types of aldimines undergo [3 4- 2] cycloaddition reactions with 2,3-butadienoates in the presence of triphenylphosphine to give 2,5-dihydrop3TToles, while that derived from SES-NSO and ethyl glyoxylate reacts efficiently with chiral sulfonimidoyl substituted bis(allyl)titaniumcorr5)lexes to give /3-alkyl-)/,5-unsaturated a-amino acid derivatives. ... 

The enantioselective 1,2-proton shift process of protic carbamate ammonium ylides was also achieved successfully. In 2011, Xu et al. reported a highly enantioselectively N—H insertion reaction of a-diazo-a-arylacetates 317 under the cooperative catalysis of rhodium and chiral spiro phosphoric acids 329 (SPA) afforded the amino acid derivatives 330 with excellent reactivities and high enantioselectivities [123]. The control experiments implied that the SPA may assist the proton-transfer process of the ylide intermediate to form an N—H insertion prodnct, thus controlling the enantioselectivity (Scheme 2.90). 

Enantioselective total synthesis of ((47J,5iS)-5-Amino-4-(2,4,5-tri-fluorophenyl) cyclohex- l-enyl)-(3-(trifluoromethyl)-5,6-dihydro-[l, 2,4]tri-azolo[4,3-a]pyrazin-7(877)-yl)methanone ABT-341 (708), a DPP4 (dipeptidyl peptidase IV) inhibitor, has been completed in diphenylprolinol silyl ether (707), in the one-pot, multicomponent, reaction of nitroalkene (704), acetaldehyde (703), vinyl phosphonate (706) and amine (705) (Scheme 178) A novel, catalytic, asymmetric Michael addition of azomethine ylide (710) with p-substituted tetraethyl alkyhdene bisphosphates (709) has been realised in the presence of a chiral copper(I)/TF-Bipham-Phos (712) complex. This system provided enantioenriched unnatural i -amino acid derivatives (711) containing gem-bisphosphonates in high yields with... 

A more common strategy for stepwise asymmetric cyclopropanation is the use of chiral electrophiles. Meyers has used bicyclic lactams (c/. Scheme 3.19, 3.20) [145,146] as electrophilic auxiliaries in sulfur ylide cyclopropanations [147]. These auxiliaries, for reasons that are not entirely clear, are preferentially attacked from the a-face. After separation of the diastereomers, the amino alcohol auxiliary may be removed by refluxing in acidic methanol or reductively [145]. This methodology has been used in asymmetric syntheses of cw-deltamithrinic acid and dictyopterene C, illustrated in the inset of Scheme 6.40 [145]. 

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