Cycloadditions amino acids

A series of chiral boron catalysts prepared from, e.g., N-sulfonyl a-amino acids has also been developed and used in a variety of cycloaddition reactions [18]. Corey et al. have applied the chiral (S)-tryptophan-derived oxazaborolidine-boron catalyst 11 and used it for the conversion of, e.g., benzaldehyde la to the cycloaddition product 3a by reaction with Danishefsky s diene 2a [18h]. This reaction la affords mainly the Mukaiyama aldol product 10, which, after isolation, was converted to 3a by treatment with TFA (Scheme 4.11). It was observed that no cycloaddition product was produced in the initial step, providing evidence for the two-step process. 

Scheeren et al. reported the first enantioselective metal-catalyzed 1,3-dipolar cycloaddition reaction of nitrones with alkenes in 1994 [26]. Their approach involved C,N-diphenylnitrone la and ketene acetals 2, in the presence of the amino acid-derived oxazaborolidinones 3 as the catalyst (Scheme 6.8). This type of boron catalyst has been used successfully for asymmetric Diels-Alder reactions [27, 28]. In this reaction the nitrone is activated, according to the inverse electron-demand, for a 1,3-dipolar cycloaddition with the electron-rich alkene. The reaction is thus controlled by the LUMO inone-HOMOaikene interaction. They found that coordination of the nitrone to the boron Lewis acid strongly accelerated the 1,3-dipolar cycloaddition reaction with ketene acetals. The reactions of la with 2a,b, catalyzed by 20 mol% of oxazaborolidinones such as 3a,b were carried out at -78 °C. In some reactions fair enantioselectivities were induced by the catalysts, thus, 4a was obtained with an optical purity of 74% ee, however, in a low yield. The reaction involving 2b gave the C-3, C-4-cis isomer 4b as the only diastereomer of the product with 62% ee. 

In an extension of this work Scheeren et al. studied a series of derivatives of N-to-syl-oxazaborolidinones as catalysts for the 1,3-dipolar cycloaddition reaction of 1 with 2b [29]. The addition of a co-solvent appeared to be of major importance. Catalyst 3b was synthesized from the corresponding amino acid and BH3-THF, hence, THF was present as a co-solvent. In this reaction (-)-4b was obtained with 62% ee. If the catalyst instead was synthesized from the amino acid and... 

The enantioselective inverse electron-demand 1,3-dipolar cycloaddition reactions of nitrones with alkenes described so far were catalyzed by metal complexes that favor a monodentate coordination of the nitrone, such as boron and aluminum complexes. However, the glyoxylate-derived nitrone 36 favors a bidentate coordination to the catalyst. This nitrone is a very interesting substrate, since the products that are obtained from the reaction with alkenes are masked a-amino acids. One of the characteristics of nitrones such as 36, having an ester moiety in the a position, is the swift E/Z equilibrium at room temperature (Scheme 6.28). In the crystalline form nitrone 36 exists as the pure Z isomer, however, in solution nitrone 36 have been shown to exists as a mixture of the E and Z isomers. This equilibrium could however be shifted to the Z isomer in the presence of a Lewis acid [74]. 

Abstract The photoinduced reactions of metal carbene complexes, particularly Group 6 Fischer carbenes, are comprehensively presented in this chapter with a complete listing of published examples. A majority of these processes involve CO insertion to produce species that have ketene-like reactivity. Cyclo addition reactions presented include reaction with imines to form /1-lactams, with alkenes to form cyclobutanones, with aldehydes to form /1-lactones, and with azoarenes to form diazetidinones. Photoinduced benzannulation processes are included. Reactions involving nucleophilic attack to form esters, amino acids, peptides, allenes, acylated arenes, and aza-Cope rearrangement products are detailed. A number of photoinduced reactions of carbenes do not involve CO insertion. These include reactions with sulfur ylides and sulfilimines, cyclopropanation, 1,3-dipolar cycloadditions, and acyl migrations. 

Silica gel [11] or alumina [11a, 12] alone, or silica and alumina together modified by Lewis-acid treatment [13] and zeolites [14], have been widely used as catalysts in Diels-Alder reactions, and these solids have also been tested as catalysts in asymmetric Diels-Alder reactions [12,13b,14]. Activated silica gel and alumina at 140 °C were used [15] to catalyze the asymmetric cycloaddition of (-)-menthyl-N-acetyl-a, S-dehydroalaninate (3) (R = NHCOMe) with cyclopentadiene in the key step for synthesizing optically active cycloaliphatic a-amino acids. When the reactions were carried out in the absence of solvent, a higher conversion was obtained. Some results are reported in Table 4.5 and compared with those obtained by using silica and alumina modified by treatment with Lewis acids. Silica gel gives a reasonable percentage of conversion after 24 h with complete diastereofacial selectivity in exo addition. 

High-pressure and thermally induced asymmetric Diels-Alder cycloadditions of heterosubstituted dienes to homochiral ot, -didehydro amino acid derivatives [82]... 

The complex obtained from commercially available chiral a-amino acids (AA) with Cu + ion induces asymmetry in the Diels-Alder reaction of 31 (R = H) with 32. By using 10% Cu(II)-AA (AA = L-abrine) the cycloaddition occurs e/iJo-stereoselectively in 48 h at 0°C with high yield and with acceptable enantioselectivity ee = 1A%). This is the first example of enantioselective Lewis-acid catalysis of an organic reaction in water [9b]. 

Waldmann H., Braun M. Amino Acid Esters As Chiral Auxiliaries in Asymmetric Cycloadditions Gazz. Chim. Ital. 1991 121 277-284... 

The intramolecular cycloaddition of munchnone intermediates (derived from the cyclodehydration of A-acyl amino acids) with 1,3-dipolarophiles was employed to construct the mitomycin skeleton. Thus, heating alkynyl acids 23 with acetic anhydride forms the intermediates 24 which undergo cyclization with loss of carbon dioxide to afford the 4-oxo-tetrahydroindoles 25 <96TL2887>... 

Scheme 10.7 1,3-Dipolar cycloadditions of nitrones with 1,1-diethoxypropene catalysed by oxazaborolidines derived A-tosyl-L-a-amino acids.

Kibayashi and coworkers have used enantiometrically pure allylic silyl ethers obtained from amino acids in cycloaddition with nitrones (Eq. 8.49).71 Cyclic nitrone reacts with a chiral allyl ether to give selectively the exo and erythro isomer (de 90%). Optically active alkaloids containing a piperidine ring such as (+)-monomorine,71c (+)-coniine,71a and (-)-oncinotine71b have been prepared from the addition product. 

Asymmetric 1,3-dipolar cycloaddition of cyclic nitrones to crotonic acid derivatives bearing chiral auxiliaries in the presence of zinc iodide gives bicyclic isoxazolidines with high stereoselectivity (Eq. 8.51). The products are good precursors of (3-amino acids such as (+)sedridine.73 Many papers concerning 1,3-dipolar cycloaddition of nitrones to chiral alkenes have been reported, and they are well documented (see Ref. 63). 

Summary N-Silylation is a crucial prerequisite for the synthesis of interesting nonnatural amino acids via cycloaddition reactions of unsaturated amines. 

Owing to flexibility in the substrate, the TycATE was also used to synthesize a variety of novel cyclic structures. Inclusion of a propargylated amino acid into the linear substrate allowed the synthesis of over 247 macrocyclic glycopeptides, where azido-sugars were coupled onto the cyclized alkyne via copper-catalyzed 1,3-dipolar cycloaddition [44] (Figure 13.12). 

The regio- and stereochemical outcome of the intermolecular 1,3-dipolar cycloaddition of an azomethine ylide generated by the decarboxylative condensation of an isatin with an a-amino acid was unambiguously determined by a single-crystal X-ray study of the spirocyclic heterocycle 49 (R1 =4-Br, R2 = H, X = CH2) <1998TL2235>. 

Dipolar cycloadditions of the unusual dipolarophiles 9-arylidenefluorenes 446 with the dipoles generated from isatin 432a and cyclic amino acid proline 433a were carried out under four different conditions to yield a series of novel dispiro oxindole derivatives 50a-f via [3+2] cycloaddition (Scheme 100) <2002T8981>. 

Scolastico s approach toward functionalized azabicycloalkane amino acids such as 407 using an intramolecular 1,3-dipolar cycloaddition strategy is a powerful way of synthesizing the linear system with good regio- and stereo-control (Equation 110) <2005JOC4124>. 

Pyranopyrrolothiazoles can be prepared in a similar way to certain pyrano- and thiopyrano-pyrrolizines and pyrrolizinopyridines as discussed earlier. Thus, thiazolidine-4-carboxylic acid reacts with the aldehyde 179 to give a 2 1 mixture of 180 and 181 (Equation 16). This reaction is a 1,3-dipolar cycloaddition of the alkene to the 1,3-dipole formed from reaction of the amino acid amine with the aldehyde <1988T4953, 1990T2213>. The alkyne analogue of 179 is similarly converted into 182 (Equation 17). 

In another variant of these intramolecular 1,3-dipolar cycloadditions, the alkyne-containing amino acid amide 183, when reacted with acetic anhydride, produces a zwitterionic thiazolo-oxazolium intermediate, which may then react intramolecularly with the dipolarophile and give the triheterocycle 184 < 1999J(P 1) 1219, 2002JOC4045> (Equation 18). The benzo-fused analogue 185 is obtained similarly (Equation 19). 

Synthetic work commenced with evaluation of an azomethine ylide dipole for the proposed intramolecular dipolar cycloaddition. A number of methods exist for the preparation of azomethine ylides, including, inter alia, transformations based on fluoride-mediated desilylation of a-silyliminium species, electrocyclic ring opening of aziridines, and tautomerization of a-amino acid ester imines [37]. In particular, the fluoride-mediated desilylation of a-silyliminium species, first reported by Vedejs in 1979 [38], is among the most widely used methods for the generation of non-stabilized azomethine ylides (Scheme 1.6). 

The ring-opening of the cyclopropane nitrosourea 233 with silver trifiate followed by stereospecific [4 + 2] cycloaddition yields 234 [129]. (Scheme 93) Oxovanadium(V) compounds, VO(OR)X2, are revealed to be Lewis acids with one-electron oxidation capability. These properties permit versatile oxidative transformations of carbonyl and organosilicon compounds as exemplified by ring-opening oxygenation of cyclic ketones [130], dehydrogenative aroma-tization of 2-eyclohexen-l-ones [131], allylic oxidation of oc,/ -unsaturated carbonyl compounds [132], decarboxylative oxidation of a-amino acids [133], oxidative desilylation of silyl enol ethers [134], allylic silanes, and benzylic silanes [135]. 

Click chemistry has been particularly active in various fields this year. For example, ample applications of click chemistry have been seen in carbohydrate chemistry. Various /weiido-oligosacchardies and amino acid glycoconjugates were synthesized via an intermolecular 1,3-dipolar cycloaddition reaction using easily accessible carbohydrate and amino acid derived azides and alkynes as building blocks <06JOC364>. The iterative copper(I)-catalyzed... 

Amino acids labeled with DNS-C1 were determined using the Ru(bpy)32+ CL reaction after HPLC separation with a reversed-phase column [104, 105], DNS derivatives are expected to produce intense CL owing to their secondary and tertiary amino groups. The detection limit for DNS-Glu was 0.1 pM (2 pmol/ injection). Although underivatized amino acids could be detected by Ru(bpy)32+ CL, the DNS derivatives showed improved detection limits by three orders of magnitude [105], An approach to convert primary amines to tertiary amines was also reported [106], In this method, divinyl sulfone (DVS) was used for a cycloaddition reaction of primary amines (Fig. 19). The DVS derivatives after HPLC separation were sensitively detected (e.g., detection limits for propylamine and 3-aminopentane were 30 and 1 pmol, respectively). 

Studies of the intramolecular cyclization of P-amino acids have included the use of camphor-derived oxazoline A-oxide 66 and a [3+2] cycloaddition reaction as a step in the formation of the amino acid with the required stereochemistry <00OL1053, OOEJOC1595>. A diastereoselective synthesis of a ip-methylcarbapenem intermediate utilises a cyclization of a P-amino acid <99CC2365>. 

The 1,3-dipolar cycloaddition of nitrile oxides and 2-methylfuran provides suitable precursors for a-amino acids such as L-furanomycin 448 that contains a dihydrofuran ring (495). By using a chiral nitrile oxide derived from mannitol bis(acetonide), the enantiomerically pure furoisoxazoline 449 has been obtained. Hydroboration-oxidation of the latter leads to the hydroxy-substituted annulated THF derivative 450, which is converted via dihydrofuran 451 to furanomycin 448 in enantiomerically pure form (Scheme 1.55). 

A concise and efficient asymmetric synthesis of L-( + )-carbafuranomycin 452, a novel analog of L-( + )-furanomycin, which is an unusual antibiotic amino acid of great interest, due to its activity as an isoleucine antagonist, has been reported (496). The synthesis starts with the 1,3-dipolar cycloaddition of a chiral nitrile oxide (obtained in situ from hydroximinoyl chloride 453 via slow addition of NEt3) with cyclopentadiene. Then methylation of cyclopentenyl acetate 454,... 

In agreement with Schemes 2.211b and 2.211c, intramolecular cycloadditions of nitrones to 5-allyl- (Scheme 2.225) or 5-homoallylproline (Scheme 2.226), are fully regio- and stereoselective. These reactions are the key steps in the synthesis of functionalized azaoxobicyclo[X.3.0] alkane amino acids, mimics of a homoSer-Pro dipeptide (721). 

The optically active isoxazolidines obtained in these cycloaddition reactions can be easily transformed into biologically active 3 -amino acids, into j3-lactams and into important chiral building blocks such as y-amino alcohols. The multitude of synthetic results in these reactions is of course expected by the wide variety... 

To carry out 1,3-dipolar cycloadditions with alkyl acrylates, nitrones of various structures such as ferrocenylnitrones (141), nitrones derived from chiral amino acids (210), L-serine-derived nitrones (660) and N -substituted C -phosphorylated nitrones (263) have been used. 

Two protected 3-amino acids, containing indolizidine and quinolizidine skeletons (607a,b), have been synthesized by using 1,3-dipolar cycloaddition of nitrones (551) and (552) to methyl ( )-5-mesyloxy-2-pentenoate. The key steps of this approach is demonstrated by novel syntheses of indolizidinone and quino-lizidinone derivatives (606a,b) and by the ring opening of the tricyclic 1,3-dipolar cycloaddition products (605a,b) (Scheme 2.268) (779). 

The a-methoxylated products are highly useful building blocks for the construction of a carbon-carbon bond a to the trifluoromethyl and diflu-oromethyl groups, which is difficult to obtain by other methods, as shown in Scheme 6.15. Thus, a-tri and a-difluoromethylated a-aminonitriles, which are precursors to the corresponding fluorinated a-amino acids, have been prepared in good yields, and flourinated homoallyanilines have been also successfully prepared [44]. in addition, tri- and difluoromethylated tetra- and dihydroquinoline derivatives can be prepared by cationic polar cycloaddition in high yields [45]. 

Recent research deals with stereoselective 1,3-dipolar cycloadditions of nitrones for the syntheses of alkaloids and aza heterocycles asymmetric synthesis of biologically active compounds such as glycosidase inhibitors, sugar mimetics, /3-lactams, and amino acids synthesis of peptido-mimetics and peptides chemistry of spirocyclopropane heterocycles synthesis of organic materials for molecular recognition and photochemical applications. 

Cross-linked polymers bearing IV-sulfonyl amino acids as chiral ligands were converted to polymer bound oxazaborolidine catalysts by treatment with borane or bromoborane. In the cycloaddition of cyclopentadiene with methacrolein, these catalysts afforded the same enantioselectivities as their non-polymeric counterparts238. 

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