Imines conjugate

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. 

Ketenes also add to imines in 2 + 2 cycloadditions giving the important g-lactams (20). The reglochemistry is predictable as the nitrogen is the nucleophilic atom in the imine. This is true even in conjugated imine (21) which gives (22) with azidoketene. The azido group can... 

The ring proton chemical shifts of 2H-pyrroles and 3H-pyrroles are as expected for conjugated imines (B-90MI201-02). 

In many cases, free imines are hydrolytically unstable. In general, it is difficult to form imines from carbonyl compounds and amines in aqueous solution. This is not always the case, and it is sometimes possible to form conjugated imines which are stabilised by delocalisation in aqueous conditions (Fig. 4-22). 

Malonaldehyde (MA) is a major end product of oxidizing or rancid lipids and it accumulates in moist foodstuffs (6). Several MA-protein systems have been studied. Chio and Tappel combined RNAase and MA to demonstrate fluorescence attributed to a conjugated imine formed by crosslinking two e-amino groups with the dialdehyde (7). Shin studied the same reaction and found it to be dependent on pH and reactant concentrations (8). Crawford reported the reaction between MA and bovine plasma albumin (BPA) also to be pH dependent, and of first order kinetics with a maximum rate near pH 4.30. At room temperature 50-60% of the e-amino groups were modified—40% in the first eight hours, the remainder over a period of days (9). 

The seven-membered metallacycles 89 (formed by ketone addition to [(butadiene)ZrCp2] cleanly add a nitrile molecule at elevated temperatures to yield the respective nine-membered metallacyclic products 96. Their hydrolysis then yields the 6-hydroxy-substituted non-conjugated unsaturated imines 97 under kinetic control. Within a few hours at room temperature these rearrange to the thermodynamically favored primary dienamine products 98.107 In this case the thermochemical diene conjugational energy makes the primary dienamines more stable than their conjugated imine tautomers (Scheme 32). 

Staudinger Reactions. Chiral oxazolidinones have been employed as the chiral control element in the Staudinger reaction as well as the ultimate source of the a-amino group in the formation of p-lactams." Cycloaddition of ketene derived from 4-(S)-phenyloxazolidylacetyl chloride with conjugated imines affords the corresponding p-lactams in 80-90% yields with excellent diastereoselectivity (eq 54). The auxiliary can then be reduced under Birch conditions to reveal the a-amino group. 

There is ample evidence that these cycloadditions involve the initial formation of a dipolar intermediate (5 Scheme 6). Conrotatory cyclization of (5) leads to the 3-lactam. Intermediates of type (5) can be trapped by another molecule of ketene to yield (d) or by sulfur dioxide to yield sulfone (7). This mechanism also explains the formation of [4 -I- 2] adducts (8) which are sometimes observed with conjugated imines. ... 

Imines derived from glyoxylic acid derivatives successfully lead to 3-lactams which are potential precursors of various antibiotics (equation 29). Conjugated imines have also been used in this context they give exclusively [2 -i- 2] cycloadducts with azido-, phthalimido-, phenoxy- and vinyl-ketene precursors (equations 30 and 31). However, [4 -i- 2] adducts are the only observed products with haloketene precursors (equation 32). - ... 

Many imines play vital roles in biological systems. A key molecule in the chemistry of vision is the highly conjugated imine rhodopsin, which is synthesized in the rod cells of the eye from 11-cis-retinal (the molecule introducing Chapter 21) and a 1° amine in the protein opsin. 

Treatment of a,p-unsaturated tosylhydrazones with NaBH4 in MeOH affords principally allylic ethers from cyclic derivatives and pyrazoles with most noncyclic examples. This divergent behavior compared to saturated tosylhydrazones has been attributedto a lessening of the electrophilicity of conjugated imine ir-bonds, which allows initial abstraction of the acidic N—H proton by BH4 to compete with reduction, and gives alternative reactions related to the Bamford-Stevens process as depicted in Scheme 4. An exception to this may be the deoxygenation of conjugated vinyl triflates (entry 11, Table 6). The cyclopropanation and elimination products produced in entry 4, Table 6 also probably arise from similar, alternative reaction paths. ... 

Addition to imines. A diastereo- and enantioselective synthesis of protected P-amino silanes is hinged on the addition of organoceriums to a-silyl SAMP/RAMP hydrazones. Conjugated imines show regioselectivity that favors the generation of allylamines. ... 

Thomas has extended the application of remote asymmetric induction to include conjugated imines (Scheme 5.2.50). ° For example, the formation of the 1,5-anP-product 224 demonstrates a matched facial... 

Aldehydes present special problems as usual. For alkylations in the a-position, the aza-enolates discussed in chapter 10 are the best. The cyclohexylimine 37 can be made in 82% yield from crotonaldehyde14 and its lithium derivative 38 reacts cleanly at the a-position with alkyl halides15 to give the non-conjugated imine 39. 

By forming adducts with azolecarbenes, cycloaddition of ketenes with imines to form P-lactams is facilitated. Azolecarhenes such as 133 and 134 induce chirahty because in the enolates (initial adducts) the elements of asymmetry can dictate the approach of the reactants. Of particular interest is the reaction between enals and conjugated imines that leads to bicylic structures. 

AROMATIC CONJUGATED IMINE/ENAMINE SUBSTRATES 3.1 a-Aryl Enamine Substrates... 

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