Substituents phthalimido

A notable exception is found in the reaction of iminium salt (35) derived from A -phthaloylglycinamide with imines (Scheme 40). The presence of the phthalimido substituent requires a modiflcation of the pro-cedure converting the adduct (36) into the p-lactam (38). While basic hydrolysis destroys compound (36), treatment with sodium hydrogensulfide smoothly gives the azeticUnethione (37) which is readily oxidized to the corresponding 3-lactam (38) with modest overall chemical yield but high enantiomeric purity. 

Alkaline hydrolysis of the acetoxy or phthalimido substituents in several derivatives of (16) affords pyrazole derivatives in ca. 60-75 /o yield, apparently via transannular ring closure, followed by alcoholysis and elimination, as shown for the acetoxy derivatives (16 Ar = Ar = Ph, X = OAc, Y = Cl, SPh). Isolation of the intermediate bicyclic enone upon acidic hydrolysis of the SPh derivative provides strong support for this mechanistic proposal (Scheme 7) <87CL157>. 

The 1-azirines obtained from the vapor phase pyrolysis of 4,5-disubstituted 1-phthalimido-1,2,3-triazoles (157) have been found to undergo further thermal reactions (71CC1S18). Those azirines which contain a methyl group in the 2-position of the ring are cleaved to nitriles and phthalimidocarbenes, whereas those azirines which possess a phenyl substituent in the 2-position rearrange to indoles. 

Although an efficient reaction, the Rees-Atkinson aziridination method suffers from two drawbacks the necessity for an N-phthalimido or N-quinazolinonyl substituent and the use of a highly toxic oxidant. Thus, recent efforts (especially in these green times) have focussed upon more benign methods for generation of the key nitrenoids. Yudin demonstrated the power of electrochemistry with a novel method that removes the need for an added metal oxidant, demonstrating an unusually and impressively broad substrate tolerance compared to many alkene aziridination reactions (Scheme 4.14) [10]. 

Other useful reagents for the preparation of tetrahydro-1,3-thiazincs with a 5-hydroxy substituent (149) are 3-chloro-295 or 3-phthalimido-296... 

The stereochemistry of the Staudinger reaction was highlighted [86] using as substrates polyaromatic imines and acetoxy, phenoxy, or phthalimido acid chloride. The stereochemistry of the resulting p-lactams seemed to vary depending on the substituents present in the imines and the acid chlorides. For instance, if the polyaromatic moiety was linked to the iminic nitrogen, the reaction produced //Y/n.v-p-lactams if the same moiety was linked to the iminic carbon, cA-p-lactams were isolated. 

Lactams with polyaromatic substituents at C-4 have been reported to be synthesized, via Staudinger reaction [99]. The reaction of polyaromatic imines with acetoxy, phenoxy and phthalimido acid chloride in the presence of triethylamine at... 

As early as 1977 Pracejus et al. investigated alkaloid-catalyzed addition of thiols to a-phthalimido acrylates, methylene azlactones, and nitroolefins [56a]. In the former approach, protected cysteine derivatives were obtained with up to 54% ee. Mukaiyama and Yamashita found that addition of thiophenol to diisopropyl mal-eate in the presence of cinchonine (10 mol%) proceeds in 95% yield and that the product, (S)-phenylthiosuccinate, was formed with 81% ee [56b]. The latter Michael adduct was used as starting material for preparation of (R)-(+)-3,4-epoxy-1-butanol. In the course of an asymmetric total synthesis of (+)-thienamycin Ike-gami et al. studied the substitution of the phenylsulfonyl substituent in the azetidi-none 69 by thiophenol in the presence of cinchonidine (Scheme 4.34) [56c]. This substitution probably proceeds via the azetinone 70. In this reaction the phenyl-thioazetidinone 71 was obtained in 96% yield and 54% ee. Upon crystallization, the optically pure substitution product 71 was obtained from the mother liquor... 

C-Acylaziridines rearrange thermally to oxazoles by way of azomethine ylides which undergo 1,5-dipolar cyclization (equation 129). Both cis- and trans- 2-benzoyl-Ar-t-butyl-3-phenylaziridine afford 2,5-diphenyloxazole. When the /V-substituent was phthalimido the intermediate betaines could be trapped as 1,3-dipolar cycloadducts with DMAD. N-Acylaziridines undergo scission of the C—N bond, followed by recyclization thus the action of aroyl chlorides on aziridines leads to oxazoles (equation 130). 

Tolkmith et al. (1967) also made a detailed investigation of the related compounds and found that the fungicidal activity of the derivatives is increased when the thiono sulfur is replaced by oxygen, or when a methylene group, an oxygen or a sulfur atom is introduced between the P and N atoms. Substituents in the phthalimido group reduce the fungicidal action. 

Tri-(9-acetyl-2-(9-methyl-a-D-gluco- (198) and -galactopyranosyl azide (199) are formed from the corresponding peracetates with trimethylsilyl azide under catalysis by SnCU, 2,3,4,6-Tetra-O-benzyl-a-D-glucopyranosyl azide has been obtained in two different ways. With other ether substituents, as for example in the formation of 2,3,4,6-tetra-0-(5-phthalimido-3-oxapentyl)-D-glucopyranosyl azide, no a-selectivity could be observed. ... 

Preparation of the 1-oxaheptam derivative, which is a true analogue of penicillins, was achieved by Wolfe. In his reaction sequence, the ring opening of penicillins and cephalosporins as described by Kukolja [23—25] is used. In the case of a phthalimido (PhtN) substituent, the 6-APA analogue (32) is formed in the reactions outlined [16]. 

The incorporation of N-phthaloyl amino acids into the dirhodium(II) platform afforded excellent asymmetric cyclopropanation catalysts [81b, 97]. In contrast to other phthaloyl catalysts [97], the X-ray crystal structure of Rh2(S-PTTL)4 (2), reported by Fox et al. revealed that the four phthalimido groups are situated on one face of the catalyst in a chiral crown structure (Figure 9.10) [93]. The four Bu- groups are directed on the other face of the catalyst, and aU C- Bu bonds are parallel to the Rh-Rh bond. Compound 2 exhibits high diastereoselectivity and yields for cyclopropanation with a-alkyl-a-diazoesters (Table 9.2, entry 2). The enantiomeric excess (ee) increases with the a-alkyl diazoester substituent size, and the highest 99% ee and 95% yield were achieved in the reaction of styrene with ethyl-2-diazo-5-methylhexanoate [93]. 

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