Arylglycines synthesis

This type of diastereoselective Petasis reaction was elaborated by Nanda et al in pyrrolidine-derived arylglycine synthesis (Scheme 8.4) [16]. 

The standard synthesis of sydnones (Section 5.03.9.2) has benefited from the use of A,./V,iV, iV -tetrabromobenzene-1,3-disulfonamide (TBBDS) as an efficient promoter of the one-pot conversion of various iV-arylglycines to sydnone products <2006H(68)2343>. Conversion of A-arylglycines to sydnones was achieved in 85 to 95% yield using a combination of NaN02 and AczO in CH2C12 promoted by TBBDS, under mild and neutral conditions. 

Since the early review on sydnones by Stewart (192) and the subsequent coverage by Potts (1), several new applications of these remarkably stable mesoionic heterocycles have been described. In particular, the synthesis of pyrazoles from sydnones has been pursued by several groups. Badachikar et al. (193) prepared several new potential antibacterials (297) from the appropriate sydnones 296, which were synthesized in the standard fashion by the cyclodehydration of the corresponding A-nitroso-A-arylglycine. 

The Pd-catalyzed amidocarbonylation was used for the synthesis of a-arylglycines that are antimicrobial agents and enzyme inhibitors.Thus, iV-acyl-a-arylglycines and other iV-acyl-a-amino acids were synthesized in highly efficient and economical manner under the standard conditions. In a similar manner, an advanced intermediate for the synthesis of antiepileptic Levetiracetam 7, iV-acetyl-a-aminobutyric acid 6, was synthesized in high yield from propanal and acetamide (Equation (1)). ... 

The enantioselective amination of iV-acyl oxazolidinones has been studied as part of a general approach to the synthesis of arylglycines. In this case, the enolization is initiated by a chiral magnesium bis(sulfonamide) complex. The oxazolidinone imide enolates are generated using catalytic conditions (10 mol% of magnesium complex) and treated in situ with BocN=NBoc to provide the corresponding hydrazide. 20 mol% of iV-methyl-p-toluensulfonamide are added to accelerate the reaction (equation 117). 

The resulting product is, however, an N-substituted oxazolidine amino acid, but this can easily be removed by either reductive or oxidative (Fig. 7) procedures. These and similar reactions can be used to prepare y-hydroxy-a-amino acids, arylglycines, a-alkyl-a-amino acids, and a variety of nonproteinogenic dipeptides (Fig. 7). The review by Muzart (58) is an excellent source of further information on the use of Cr compounds in organic synthesis. 

Several reports have employed a more traditional approach where the use of enantio-pure chiral amino auxiliaries, that, after the successful Strecker reaction, can be chemically modified to yield the free amino acids. For example, Chakraborty and co-workers have reported the highly diastereoselective addition of trimethylsilyl cyanide to a variety of a-phenylglycinol-derived benzaldimines [16]. (S)-a-Methylbenzylamine has been used as a chiral auxiliary for the asymmetric Strecker reaction [17]. (R)-Phenylglycinol has been utilized as a chiral auxiliary from the asymmetric Strecker reaction products of aldehydes in the synthesis of a,a-disubstituted amino acids [18]. (R)- and (S)-2-Amino-2-phenylethanol were used as chiral auxiliaries in the synthesis of optically pure a-arylglycines [19]. 

In a radically different approach, Alper has discovered that Me-DuPhos may be used in the synthesis of a-amino acids through a palladium-catalyzed double carbohydroamination whereby aryl iodides 74 can be converted to the corresponding arylglycine amides 75 in the presence of excess primary amine (Scheme 13.27).72... 

A catalytic approach to the synthesis of arylglycines was proposed by Evans and coworkers using enantioselective amination of iV-acy 1 oxazolidinones [54], Metallo-bis(sulfonamide) complexes derived from chiral diamines are potential chiral catalysts. The magnesium-bis(sulfonamide) complex 109 was generated by treating (S,S)-bis(sulfonamide) 108 with dimethylmagnesium in dichloromethane (Scheme 50). 

Other reports for the boron-Mannich reaction include the synthesis of aminophenol derivatives,561 a-arylglycines,576 a growth hormone secretagogue NN703,577 a polyhydroxyindolizine alkaloid uniflorine A,578 and cyclic ct-amino acids.579 The reaction has been applied to solution-phase reactions580 and the solid-phase reaction581-585 for the synthesis of libraries of peptides, a-amino acids, and bicyclic diketopiperazines. The reactions were accelerated by the irradiation of microwave.586... 

Hydrogenation of the azide moiety readily provides the amine using Palladium on Carbon and H2 or Tin(II) Chloride. This methodology has been extended to the synthesis of arylglycines (eq 26). ... 

Petasis, N. A., Goodman, A., Zavialov, I. A. A new synthesis of a-arylglycines from aryl boronic acids. Tetrahedron 1997, 53,16463-16470. 

The observation that palladium could also catalyze this process enhanced the scope of amidocarbonylation reactions.24 This method provided ready access to the arylglycine building block 39, from benzaldehyde 37 and amide 38, required for the synthesis of the chloropeptins 36 that have been shown to possess anti-HIV activity. 

The synthesis of the B-ring arylglycine piece proceeded along similar lines as the A-ring fragment, but since this piece possessed... 

Apart from yielding arylglycines, chiral oxazolidinones also provide a powerful tool with which to stereoselectively fashion protected p-hydroxy tyrosines such as the C-ring building block 63. As indicated in Scheme 30, the critical element of this variant of substrate-controlled enantioselective synthesis is the inventive use... 

Recently, Ellman expanded the scope to include N-tert-butyl imino esters 60 (Scheme 8.16) [42]. The resulting arylglycines 61, which are unnatural amino acids, are interesting chiral building blocks that might find application in peptide synthesis. 

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