Cyclic imino esters

A wide variety of /3-lactams are available by these routes because of the range of substituents possible in either the ketene or its equivalent substituted acetic acid derivative. Considerable diversity in imine structure is also possible. In addition to simple Schiff bases, imino esters and thioethers, amidines, cyclic imines and conjugated imines such as cinnamy-lidineaniline have found wide application in the synthesis of functionalized /3-lactams. A-Acylhydrazones can be used, but phenylhydrazones and O-alkyloximes do not give /3-lactams. These /3-lactam forming reactions give both cis and /raMS-azetidin-2-ones some control over stereochemistry can, however, be exercised by choice of reactants and conditions. 

The aldehyde (10 mmol) in MeCN (5 ml) is stirred with the imino ester (I0 mmol), anhydrous K2C03 (0.14 g) and TEBA-C1 (0.23 g, 1 mmol) in MeCN (10 ml) at room temperature until the mixture solidifies. HzO (60 ml) is added and the solid is separated, washed well with H20 and recrystallized (if the cyclic product does not solidify, the mixture is extracted with Et20 (2 x 25 ml). The combined extracts are washed with H20 (25 ml), dried (MgS04) and evaporated to yield the product). 

It is noteworthy that stereoselectivities were high, even with sterically demanding substituents at the double bond. Similarly, the treatment of the cyclic bis (allyl) titanium complexes 18 with the imino esters 23a-c afforded the corresponding B-syn-configured cyclic unsaturated amino acid derivatives -25 and the Z-syn-configured isomers Z-25 with >98% regioselectivity and >98% diaste-reoselectivity in good yields. 

Table 1.3.5 Reaction of the cyclic mono(allyl)titanium complexes 20 with the imino ester 23c.

Imino esters derived from benzoyl, nitro and ester-substituted acetonitriles behave as ketene A O-acetals in yielding 1,1-enediamines when reacted with amines29,89,90. For example, cyclic 1,1-enediamines 8 have been prepared by the reaction of imidates 54 and diamines (equation 19)29. 

Common synthetic methods for the preparation of cyclic 8-enamino esters are the condensation between a lactim ether and benzyl cyanoacetate followed by hydrogenolytic decarboxylation, or the imino ester carbon-carbon condensation with tert-butyl cyanoacetate followed by a trifluoroacetic acid treatment. The use of a thiolactam condensed with ethyl bromoacetate gives, after sulfur extrusion by triphenylphosphine, cyclic 8-enamino esters. Compared with these methods, the Meldrum s acid condensation followed by the monodecarboxylating transesterification described here is more convenient and practical. An extension of this procedure permits preparation of smaller... 

From acid amides, lactamidines and cyclic imino esters 575... 

NR2 R — X NR2 R — 0R3 X = halogen Imidoyl halides Imidic acid esters (imidates, imino esters) Lactimidic acid esters Cyclic imidates 1-3,7 7, 15, 16 17 12, 19... 

The Ley group investigated a highly enantioselective Mannich reaction of carbonyl compounds with a-imino esters catalysed by 5-pyrrolidin-2-yltetrazole 5a. Using various cyclic and acyclic carbonyl compounds, products were obtained with high stereocontrol (95 to >99% ee and >19 1 dr) (Scheme 9.39). 

On the other hand, the Gong group reported the enantioselective [l,5]-hydride transfer/cyclization reaction between ortho tertiary amine substituted aromatic keto esters 33 and aromatic amines 34 catalyzed by chiral bisphosphoric acid (1 ,1 )-C8, developed in their own group (Scheme 4.16). In this reaction, the in situ formed a-imino esters 36 act as the hydride acceptors, allowing the efficient synthesis of cyclic aminals 35 in high stereoselectivity (up to 14 1 dr, 90% ee). 

Scientists at Teijin Ltd., patented [196,197] and published extensive studies on [162-167] the use of bis(cyclic imino ethers) and bis(cyclic imino esters) as chain extenders for PET. 

A number of classes of additives specifically for use as UV absorbers in polymer formulations are available including, among the better known ones, aromatic salicylates [11], o-hydroxybenzophenones [12], 2-hydroxyphenylbenzotriazoles [12,13], derivatives of cinnamic acid and related materials [14,15], aromatic oxanilides [16], cyclic imino ester derivatives known varionsly as benzoxazines or benzoxazones [17, 18] and hydroxyphenyltriazines [19]. 

Cyclic imino esters were originally developed as PET chain extenders (see Section 6.4.2) but the UV-stabilising ability of some members of the family was noted. The mechanism of energy dissipation is not totally clear, but may involve ring opening and closing cycles in the excited state to achieve a similar effect to the excited state tautomerism of other UV absorbers. 

Cyclic imino esters were originally developed, at least in terms of plastics additives, as chain extenders for polyesters (see Section 6.4.2). The same company involved in this research, Teijin, discovered that some of these compounds, most notably 2,2"-p-phenylene-bis(3,l-benzoxazin-4-one), were effective UV absorbers [97]. It was also noted by the inventors that if the additive reacted with chain ends in a polyester or polyamide, this could result in a diminution of the UV protective ability of the additive. Careful compounding, with as low... 

Soon afterward, MacMillan s group properly explored this organocatalytic reductive amination, observing that the ortho-triphenylsilyl phosphoric acid 17n in the presence of 5-A MS facilitates the desired coupling of acetophenone and 4-OMe-aniline in high conversion and with excellent levels of enantiocontrol at 40 C (87% yield, 94% ee) [55]. Authors report also the reduction of the pyruvic acid-derived cyclic imino ester with excellent enantioselectivity. However, implementation of the corresponding ethyl-substituted imine resulted in a dramatic decrease in... 

Other defects that may occur in polyAN include acrylamide (10) and acrylic acid (11) units, resulting from adventitious hydrolysis of AN units, and also derived cyclic structures such as anhydrides (12), imino-amides (13) and imino-esters (14). These structures give rise to characteristic additional peaks in the and NMR spectra of the polymer and they also contribute to the purely aliphatic regions of the spectra [68-70]. 

The same authors have designed novel chiral pyrrolidine-based amino sulfonamides, which were applied to promote a n -Mannich reactions of A/-PMP-protected a-imino esters with aldehydes, giving comparable results to those obtained with the binaphthyl-based amino sulfonamide catalyst. However, these novel pyrrolidine-based amino sulfonamides were found to be capable of promoting a //-Mannich reactions between A/-PMP-protected a-imino esters and a range of cyclic as well as acyclic ketones with excellent yields, enan-tioselectivities combined with moderate to high diastereoselectivities of up to 90% de (Scheme 3.13). 

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