Phthalimides, reaction with ketones

Allylmagnesium bromide, 41, 49 reaction with acrolein, 41,49 5-AUyl-l,2,3,4,5-pentachlorocydopen-tadiene, 43, 92 Allyltriphenyltin, 41, 31 reaction with phenyllithium, 41, 30 Aluminum chloride, as catalyst, for isomerization, 42, 9 for nuclear bromination and chlorination of aromatic aldehydes and ketones, 40,9 as Friedel-Crafts catalyst, 41, 1 in preparation of mesitoic acid, 44, 70 in preparation of 2u-thiohomo-phthalimide, 44, 91... 

A new route to bromopyrroles was developed. It depends on addition of HBr to A-protected y-aminoynones. When applied to alkynyl ketones, 2-aryl or 2-alkyl 4-bromopyrroles are formed. 2-Alkyl or 2-aryl 3-bromopyrroles can be obtained from acetals of V-aminoynals. The ketones are made from A -protected propargylamines by ( -acylation. The acetals are made from 3,3-diethoxypropyne by addition to an aldehyde followed by introduction of the amino group by reaction with phthalimide under Mitsunobu conditions. <95S276>... 

Alkynyl ketones can be formed from addition of alkynyllithium or Grignard reagents to phthalimides and then the products converted into pyrazoles by reaction with hydrazines. For example, A -alkyl-substituted phthalimides 633 were easily transformed to mono-, di-, or trisubstituted pyrazoles 634 via a one-pot addition/decyclization/cyclocon-densation process (Equation 131) <2002J(P1)207>. A -Alkyl-substituted phthalimides 635 were easily converted into di-, tri-, and tetrasubstituted pyrazoles 636 via a one-pot addition-decyclization-cyclocondensation process (Equation 132) <2003H(60)2499>. 

For the preparation of Gly- j/-[CF=CH]-Pro in relation to the study of cyclophilin A inhibitors, Welch and co-workers employed the Peterson reaction of a-fluoro-a-trimethylsilyl acetate (15a,b) with ketone 10. E/Z selectivity was found to be influenced by the ester part of the acetate (see Scheme 10.4) [15]. The reaction of tert-butyl ester 15a gave almost an equal amount of the isomers (lib, E Z= 1 1.1), while moderate E selectivity was observed when trimethylphenyl ester 15b was used (11c, E Z= 6 1). Conversion of ester Z-llb to amino derivative 16 was achieved via the Mitsunobu reaction of phthalimide with the alcohol formed by the DIBAL-H reduction of Z-llb. 

Amino acids are prepared from aldehydes and ketones via reaction with ammonia and HCN or via reactions of halo-acids with ammonia or amines. Phthalimide is a useful amine-nucleophile surrogate for the preparation of amino acids. 

The reductive coupling of phthalimides with ketones and aldehydes in THF by low-valent titanium generated from Zn-TiC gave 3-hydroxy-3-(l-hydroxyaIkyl)-isoindolin-l-ones as two-electron reduced products and alkyhdene-isoindolin-l-ones as four-electron reduced products. These could be obtained selectively by controlling the reaction conditions. The geometric ratios of the alkylideneisoindolin-l-ones obtained from phthalimides and aldehydes could be increased by reflux in PPTS/ toluene (catalyst). In particular, the Z-isomers of A-unsubstituted alkylideneisoindolin-l-ones could be obtained exclusively. 

The reactions of dimethyl phenylphosphonite with acid chlorides, a-halogeno-ketones, and iV-(bromomethyl)phthalimide have been used to prepare acyl phos-phinates, /3-keto-alkylphosphinates, and phthalimidomethylphosphinates as intermediates in the synthesis of a-diazophosphinic esters.39 a-Amino-phosphonates have also been prepared by the addition of secondary phosphites to nitriles40 and to isocyanides.41... 

This stabilization of the radical intermediates, arising from a better mesomeric stabilization of radicals in the phthalimide moiety, consequently increase the exoenergicity of reactions and, according to the Bell-Evans-Polanyi principle, lowers the activation barrier and thus enables processes that are unknown from ketones. The unique photochemical reactivity of phthalimides will be demonstrated with some examples. 

Interestingly, imides possess a photochemical behavior that is very similar to that of ketones. Especially, phthalimides behave like phenyl ketones with respect to some of their photophysical properties. Despite many similarities there are at least three important differences. First, phthalimides are more prone to photoelectron transfer (PET) processes than ketones. This property was very successfully applied in the synthesis of a variety of amino acid derivatives (see Section 6.2.3.2). Second, the cyclization of imides often affords 0,7V-acetals as primary products, and this obviously has some consequences for the stability and the follow-up reactions of these products. Third, in contrast to aryl ketones, phthalimides are not quantitatively converted into the triplet state, and thus they may react both from the singlet and the triplet excited state. 

The same group expanded the scope of the reaction treating cyclic p-keto phos-phonates and catalyst 17c with different A-(arylthio) phthalimides (Scheme 14.27) [77]. Fairly good results in terms of yield and enantiocontrol were achieved for the first preparation of the thiophosphonates in enantiomerically enriched form. It is interesting to note that noncovalent activation provided by diaryl prolinols expands the potential of secondary amines in promoting asymmetric reactions of carbonyl compounds other than simple aldehydes and ketones. A major limitation of all... 

Because the reactions of related in -cyclohexadienyl complexes are synthetically valuable, the reactions of this ligand have been studied extensively. An outline of how this chemistry can be conducted on the Fe(CO)j fragment is shown in Equation 11.51. A variety of cyclohexadienes are readily available from Birch reduction of substituted aromatics. Coordination and abstraction of a hydride, typically by trityl cation, leads to cationic cyclohexadienyl complexes. These cyclohexadienyl complexes are reactive toward organolithium, -copper, -cadmium, and -zinc reagents, ketone enolates, nitroal-kyl anions, amines, phthalimide, and even nucleophilic aromatic compounds such as indole and trimethoxybenzene. Attack occurs exclusively from the face opposite the metal, and exclusively at a terminal position of the dienyl system. This combination of hydride abstraction and nucleophilic addition has been repeated to generate cyclohexa-diene complexes containing two cis vicinal substituents. The free cyclohexadiene is ttien released from the metal by oxidation with amine oxides. ... 

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