Boronic amino acid complexes

Boroxazolidinones are zwitterionic boron-amino acid complexes that can be used for the simultaneous protection of the a-amino and a-carboxy groups (Scheme Treatment of... 

The enantioselective inverse electron-demand 1,3-dipolar cycloaddition reactions of nitrones with alkenes described so far were catalyzed by metal complexes that favor a monodentate coordination of the nitrone, such as boron and aluminum complexes. However, the glyoxylate-derived nitrone 36 favors a bidentate coordination to the catalyst. This nitrone is a very interesting substrate, since the products that are obtained from the reaction with alkenes are masked a-amino acids. One of the characteristics of nitrones such as 36, having an ester moiety in the a position, is the swift E/Z equilibrium at room temperature (Scheme 6.28). In the crystalline form nitrone 36 exists as the pure Z isomer, however, in solution nitrone 36 have been shown to exists as a mixture of the E and Z isomers. This equilibrium could however be shifted to the Z isomer in the presence of a Lewis acid [74]. 

The enantioselective inverse electron-demand 1,3-dipolar cycloadditions of nitrones with alkenes described so far are catalyzed by metal complexes that favor a monodentate coordination of the nitrone, such as boron and aluminium complexes. However, the glyoxylate-derived nitrone 256 favors abidentate coordination to the catalyst, and this nitrone is an interesting substrate, since the products that are obtained from the reaction with alkenes are masked ot-amino acids (Scheme 12.81). 

Several complexes have been tested for potential pharmaceutical applications and some of them have been introduced into practice.84,126 Isolation of antibiotics of boron complex type (Section 24.3.3.2) and results obtained with carboxyborane complexes that are analogues of amino acids (Section 24.2.2) are likely to stimulate further studies. Quite a few boron complexes have found application in 10B neutron capture therapy based on the 10B(n, a)7Li nuclear reaction.84,126,172... 

A series of metal complexes containing trimethylamine boranecarboxylato ionligand [103904-11-6], (CH3)3N BH COO, have been prepared with Co (III), Co (II), Zn(II), Ca(II), Cr(III), and Fe(III) (39,40). This ligand, derived from the boron analogue of the amino acid glycine, behaves similady to organic carboxylato ligands. 

It is believed that most of the transition metals are complexed to nitrogen donors, such as are found in amino acids or derivatives of chlorophyll, and that the metals with high ionic potentials, such as beryllium, boron, germanium, titanium, gallium, and major elements such as aluminum and silicon, may be bonded to oxygen donors of degraded lignin. 

In a parallel study, Wipf and Fritch11041 have shown that also urethane-protected (Boc), and even amino acid segments, are tolerated as acyl compounds on the aziridine nitrogen. The best results were obtained with alkylcopper reagents derived from CuCN and an alkyl-lithium in the presence of boron trifluoride-diethyl ether complex. Some 6-alkylated compounds (11-15%) were isolated as well. This work was extended to a solid-phase procedure that resulted in resin-bound alkene isosteres that could immediately be used in further peptide synthesis.11051 For this purpose, the 2-nitrophenylsulfonyl (oNbs) group was used for nitrogen protection and aziridine activation. It could be readily cleaved with benzenethio-late, which was compatible with the acid-sensitive Wang linker used. 

I would emphasize that the reaction of the amino acid-carbene complex with boron tribromide represents a good possibility of again cleaving the carbenyl protective group under extremely mild conditions at —25°C. 

The use of CABs prepared from the sulfonamides of amino acids to introduce asymmetry into the Diels-Alder reaction was reported simultaneously by Takasu and Yamamoto [14] and by Helmchen and co-workers [13]. Because of the capacity of boron to complex the carbonyl moiety in this type of eatalyst, it is clear they might be effective in promoting the reaction of silyl ketene acetals with various aldehydes. 

While aromatic aldimines of amino acid esters are readily accessible from benzaldehyde or related derivatives and amino acid esters with concomitant removal of water,the corresponding ketimines require harsher reaction conditions, e.g. the benzophenone imine of glycine methyl ester is formed in boiling xylene in the presence of boron trifluoride-diethyl ether complex as a Lewis acid in 82% yield.P l These or similar reaction conditions lead also to piperazine-2,5-dione (DKP) formation therefore milder reaction conditions have been developed such as the transimination with benzophenone imine in dichloromethane, which occurs at room temperature overnight in 80-95% yield (Scheme The N -diphen-... 

The Nicholas reaction was used to synthesize the p-lactam precursor of thienamycin in the laboratory of P.A. Jacobi and thereby accomplish its formal total synthesis. The necessary p-amino acid was prepared by the condensation of a boron enolate (derived from an acylated oxazolidinone) with the cobalt complex of an enantiopure propargylic ether. The resulting adduct was oxidized with ceric ammonium nitrate (CAN) to remove the cobalt protecting group from the triple bond, and the product was obtained with a 17 1 anti.syn selectivity and in good yield. 

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