Imine cyclic

In addition to their antiknock properties, organic lead compounds possess bactericidal properties and motor fuels with lead are known to inhibit bacterial growth during storage in contact with water. With the disappearance of lead-based compounds, it is necessary to incorporate biocides from the cyclic imine family, (piperidine, pyrrolidine, hexamethyleneimine), alkylpropylene diamines or imidazolines (Figure 9.2). 

Amines undergo aminopalladation to alkynes. The intramolecular addition of amines to alkynes yields cyclic imines. The 3-alkynylamine 273 was cyclized to the 1-pyrroline 274, and the 5-alkynylamine 275 was converted into the 2,3,4,5-tetrahydropyridine 276[137]. Cyclization of o-(l-hexynyl)aniline (277)... 

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. 

JA468>, and the 3-imino-l-azetine (205 Ar = p-FC6H4) has imine absorptions at 1600 and 1715 cm , assigned to the endo- and exo-cyclic imine functions respectively (74ZN(B)399>. 

Imines with an electron-withdrawing group at the nitrogen atom are excellent acceptors for the acetate (1) or the carbonate (13) [36]. Thus, N-tosylimines (84) gave very good yields of pyrrolidines (85) under typical conditions. The strained cyclic imine (86) and a,/ -unsaturated imine (87) both participated smoothly in the cydoadditions. The hindered nitrimine (88) also reacts well with (1) (but not with 13) to produce the pyrrolidine (89) with a 17 1 diastereoselectivity. However, the unhindered nitrimines from cyclohexanone and 2-nonanone failed to react presumably due to enolization (Scheme 2.24). 

Azirines (three-membered cyclic imines) are related to aziridines by a single redox step, and these reagents can therefore function as precursors to aziridines by way of addition reactions. The addition of carbon nucleophiles has been known for some time [52], but has recently undergone a renaissance, attracting the interest of several research groups. The cyclization of 2-(0-tosyl)oximino carbonyl compounds - the Neber reaction [53] - is the oldest known azirine synthesis, and asymmetric variants have been reported. Zwanenburg et ah, for example, prepared nonracemic chiral azirines from oximes of 3-ketoesters, using cinchona alkaloids as catalysts (Scheme 4.37) [54]. 

According to these transition state models2,. (y -products are formed via a chair (C) conformation where both the enolate and the imine are in E geometry (E,E) or via a boat (B) transition state where the enolate is in Z and the imine in Econfiguration C(E.E) or B(Z,E). antt-Products are formed via B(E,E) and C(Z,E) transition states. The transition states leading to 1 and 2 are based upon the more stable E geometry of the imine. For cyclic imines a complementary set of transition states can be applied based on the Z geometry of the imine. 

Table 2 Reaction of chromium alkoxycarbenes with cyclic imines...

Addition of Grignard reagents or organolithium reagents to co-halo nitriles leads to 2-substituted cyclic imines. 

MeON=CH(CH2)3CHO with BusSnH and AIBN, for example led to trans-2-(methoxyamino)cyclopentanol in good yield.Addition of radical to the C=N unit of R—C=N—SPh or R—C=N—OBz led to cyclic imines. Radical addition to... 

Heteroatom rings, such as that found in quinoline derivatives, can be generated from amino-ketones with [hydroxy(tosyloxy)iodo]benzene and perchloric acid. Cyclic imines are converted to pyridine derivatives with NCS and then excess sodium methoxide. ... 

Dipolar cycloaddition of azides with olefins provides a convenient access to triazolines, cyclic imines, and aziridines and hence is a valuable technique in heterocyclic synthesis. For instance, tricyclic -lactams 273 - 276 have been synthesized using the intramolecular azide-olefin cycloaddition (lAOC) methodology (Scheme 30) [71]. 

Scheme 36. The urea derivative gave similar results to the thiourea compound. Acyclic imines (mainly E isomers) and Z cyclic imines could also be used for this process (Scheme 40,91% ee) [148,152,154].

Several possible models can be discussed for the molecular basis of slow inhibition, but experimental evidence in support of one or the other is still lacking for glycosidases. A reversible chemical reaction at the active site, for example, formation of the cyclic imine 3 or a diffusion-controlled association with a trace of 3 in equilibrium with the 5-araino-5-deoxypyranose 1 can be precluded, because slow inhibition is also observed with 1-deoxynojirimycin and its analogs and with acarbose (see Section II,2,d) and indoli-... 

Organolanthanides are efficient catalyst precursors for the regioselective (>95%) IH of primary aminoalkynes, forming five-, six-, and seven-membered cyclic imines via Exo-Dig processes (Eq. 4.86) [303, 304]. 

The same group extended this work to a cyclic imine (Scheme 5-47) better results were obtained with heterobimetallic lanthanide catalysts than with chiral titanium alkoxides. 

Scheme 5-47 Asymmetric hydrophosphonylation of a cyclic imine catalyzed by heterobimetallic rare earth/alkali metal/BI-NOL complexes or by chiral titanium alkoxide complexes...

Asymmetric hydrosilylation of the cyclic imine 17 (Approach A) was precedented on simpler substrates by Buchwald but the method requires an expensive and highly air-sensitive chiral htanocene catalyst (Scheme 8.5) [6]. 

Scheme 8.5 Buchwald s example of asymmetric hydrogenation of cyclic imine.

Asymmetric hydrogenation of a cyclic enamide (Approach B) had very sparse literature precedents [7]. It should also be noted that preparation of these cyclic imines and enamides is not straightforward. The best method for the synthesis of cyclic imines involves C-acylation of the inexpensive N-vinylpyrrolidin-2-one followed by a relatively harsh treatment with refluxing 6M aqueous HC1, which accomplishes deprotection of the vinyl group, hydrolysis of the amide, and decarboxylation (Scheme 8.6) [8]. 

Scheme 8.6 Known preparation method for cyclic imines.

Disilene 21 can react with the C=N bond in a cyclic imine 73 and cumulenes such as carbodiimide75 and keteneimine74 (Eqs. 18-21). The reactions with cumulenes are not straightforward, although the initial products are most likely [2 + 2] cycloadducts. 

The latter sequence, as reported by Overkleeft, van Boom and coworkers, employs substrates of type 9-42 containing both azide and aldehyde functionalities. Treatment of 9-42 with PMe3 in MeOH at room temperature forms a cyclic imine 9-43 via an intermediate phosphazene. Following the addition of an acid and an isocyanide 9-43, products of type 9-44 are obtained. According to this scheme, enan-tiopure carbohydrate-derived azido aldehydes 9-45 and 9-48 led to the morpholino compounds 9-46 and 9-47, as well as to the pipecolic acid scaffolds 9-49 and 9-50, re-... 

It should be noted that the group of Martens has also produced pipecolic acid derivatives, although in their Ugi-3CR approach pre-formed cyclic imines were employed as the starting materials [40]. 

Annelation of cyclic imines with /3-dicarbonyl compounds <2004RCB393>, with cyclic /3-oxodithioesters <20010L229>, or with arylmethylene-/3-dinitriles <2002SC581> provides a one-pot route to quinolizidine systems, as exemplified in Equation 11 for the preparation of the 8-azasteroid 322. 

The asymmetric hydrogenation of acyclic imines with the ansa-titanocene catalyst 102 gives the chiral amines in up to 92% ee.684,685 This same system applied to cyclic imines produces the chiral amines with >97% ee values.684,685 The mechanism of these reductions has been studied 686... 

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