Substrates phthalimides

Among compounds other than simple alkyl halides a halo ketones and a halo esters have been employed as substrates m the Gabriel synthesis Alkyl p toluenesul fonate esters have also been used Because phthalimide can undergo only a single alkyl ation the formation of secondary and tertiary amines does not occur and the Gabriel synthesis is a valuable procedure for the laboratory preparation of primary amines... 

A less obvious scheme that can lead to a bell-shaped curve has been recognized by Zemer and Bender. The substrate is a weak acid or base, but possesses only one ionizable group, and no other ionizable reactant is involved (other than water). The second inflection in the curve is ascribed to an ionizable group created in an intermediate. An example has been discovered in the hydrolysis of o-carboxy-phthalimide ... 

The reactions 33 between tetrachloro-A-n-butylphthalimide (113) and n-butylamine275 in aprotic and apolar media (cyclohexane, benzene, toluene, xylenes) show a third experimental reaction order in the amines explained by the formation of a complex (n-jr-like) between the electron acceptor substrate (the derivative of the phthalimide) and the electron donor nucleophile (the amine). In mixed solvents (such as the mixtures cyclohexane/aromatic solvents) the kinetic investigation reveals the presence of a competition between the electron donor solvent and the amine in complexing the substrate. 

While reaction of the acetate 40 as well as the acetyl- and phthalimide derivatives of chiral amine (41b and 41c) proceeded with erythro diastereoselectivity (in accordance with the classical cis effect, minimization of 1,3-allyhc strain) (Table 6, entries 8, 10, 11), for the allylic alcohols 39, primary allyhc amine 41a, silyl enol ethers 42 and enol ether 43 threo selectivity was observed (Table 6, entries 1-7, 9, 12-14) (see also Scheme 24). For allyhc alcohols with an alkyl group R cis to the substituent carrying the hydroxyl group, diastereoselectivity was high (Table 6, entries 1-7) in contrast, stereoselection was low for allylic alcohols which lack such an R cis) substituent (substrates 39h and 39i, see Figure 4). 

In general, amino-containing compounds are poor partners in CM due to their tendency to coordinate to the metal catalyst, even when late-transition metal systems are employed. To preserve catalyst activity, amino groups are therefore typically masked as cyanides, carbamates, amides, or phthalimides. In substrates where iV-coordination to the catalyst is less favored, such as with hindered /V-aryl-/V-allylamines, no protecting group is required. 

The reaction with ammonia or amines, which undoubtedly proceeds by the SNAr mechanism, is catalyzed by copper8" and nickel105 salts, though these are normally used only with rather unreactive halides.106 This reaction, with phase transfer catalysis, has been used to synthesize triarylamines.107 Copper ion catalysts (especially cuprous oxide or iodide) also permit the Gabriel synthesis (0-58) to be applied to aromatic substrates. Aryl bromides or iodides are refluxed with potassium phthalimide and Cu 0 or Cul in dimethylacetamide to give N-aryl phthalimides, which can be hydrolyzed to primary aryl amines.108... 

The activity and enantioselectivity of chiral Ir catalysts have been tested by using 2,3,3-trimethylindolenine as a model substrate. Hydrogenation of the cyclic imine with [Ir(bdpp)Hl2 2 gives the corresponding chiral amine with 80% ce (Scheme 1.99) [350]. The stereoselectivity is somewhat better than that with acyclic substrates (see Scheme 1.94). A neutral BCPM-Ir complex with Bil3 effects asymmetric hydrogenation in 91% optical yield [354], A complex of MCCPM shows similar enantioselection [354], These complexes are not applicable to the reaction of other acyclic and six-membered cyclic imines. An MOD-DIOP-Ir complex is also usable with the aid of ( -C4H9)4NI [355], An Ir complex of BICP with phthalimide effectively... 

Asymmetric hydrogenation of Scheme 1.101 provides a general route to isoquinoline alkaloids (see Section 1.3.1.1). An imine substrate is hydrogenated with the chiral titanocene (/ )-34 to give the S product with 98% ee [346a,b,352], A neutral BCPM-Ir complex with phthalimide in toluene also shows high enantioselection [358]. The choice of a weakly polar... 

The enantioselective complexation technique can also be applied as one step in the reaction sequence, providing chiral substrates for the next step. We will now discuss the example of Gabriel synthesis between potassium phthalimide 41 and alkyl bromide 42, which leads to optically active amines (Scheme 1) [51], Instead of the complicated preparation of chiral alkyl bromides (halides), imides (43), which are reaction intermediates, have been resolved. Upon treatment with hydrazine and KOH, these gave optically active amines. The chiral host (S,S)-(-)-6 or the chiral biaryl host (,S>(-j-40 was used for the effective resolution of the intermediates 43. Racemic mixtures 43a-d were resolved by complex formation with the host (S,S)-(-)-6 in a mixture of diethyl ether and light petroleum. 

Amino-6-methyl-1,6-naphthyridin-5(6//)-one (17) with (V-(4-iodopentyl) phthalimide gave 6-methyl-8-(l-methyl-4-phthalimidobutyl)amino-l,6-naphthyridin-5(6//)-one (18, R = phthalimido) (substrate, Me2NCHO, 80°C, A, synthon + NEt3 in during 4 h 85°C, 2 h 45%) and thence, by deprotection with hydrazine, 8-(4-amino-l-methylbutyl)amino-6-methyl-l,6-naphthyridin-5(6//)-one (18, R = NH2).1116... 

Vinyl epoxides can also be used as substrates for formation of optically active allyl amines catalyzed by the same type of chiral palladium complexes as in Eq. (10). By reaction of simple vinyl epoxides with phthalimide as the nitrogen source in the presence of the chiral palladium complexes as the catalyst, very high ee (> 98 %) and regioselectivity (> 97 %) were obtained [26]. A variety of different applications of the use of the palladium-catalyzed approach for the formation of allyl amines and the use of this in total synthesis has been pursued by several research groups, and further details can be obtained in a review by Trost et al. [19d]. 

The phthalimide anion is a strong nucleophile, displacing a halide or tosylate ion from a good Sn2 substrate. Heating the /V-alkyl phthalimide with hydrazine displaces the primary amine, giving the very stable hydrazide of phthalimide. 

Table 8. Phthalimide Anion Displacement Reactions with 2-(2-Bromoacyl)-2-ethyl-1,3-dithiane 1-Oxide Substrates...

The three component aminoallylation reaction of the activated olefins 4 was also reported by us (Scheme 7) [39]. The palladium catalyzed reaction between phthalimid 10, olefins 4 and allyl chloride 11 proceeded well in the presence of CS2CO3 to give the corresponding aminoallylation products 12 in high yields. Likewise, cyanoallylation of activated olefins was also reported (Scheme 8) [40]. In both cases only aryl substituded and f-bulyl substituded olefins are proved good substrates. The mechanism of these reactions is presumably similar to that of hydroalkoxylation reaction (see Scheme 5). 

In this study, we have used a set of polyimide model molecules to obtain information about possible interactions at the polyimide copper interface. Benzene, phthalimide (PIM), benzene-phthalimide (BPIM), methyl-phthalimide (MPIM), and malonamid (MAM) were deposited in ultrahigh vacuum (UHV) onto clean polycrystalline copper substrates, and the measurements were performed by means of XPS and UPS. 

The course of the intramolecular photoreaction of carbonyl compounds with electron-rich alkenyl- or aryl-substituents in the side-chain is dictated essentially by the thermodynamics of the electron-transfer step. This relationship has been intensively studied for phthalimides. When AG°et is positive, [n 2 + 2] cycloaddition reactions were observed with alkenyl substituents and classical Norrish II chemistry for aryl-substituted substrates. When AG°et was negative, electron transfer prod-... 

Intramolecular PET cyclizations of aminoalkyl-substituted phthalimides were investigated by the groups of Kanaoka and Coyle [168-171]. Because of the relatively low oxidation potentials of tertiary amines, these electron-transfer reactions are highly exergonic [172, 173]. The regioselectivity of the CH-activation step was remarkably high for the A -methyl, A -phenyl substituted substrates (Scheme 43). 

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