Imines aliphatic

Catalysts prepared either from VAPOL (109) or from VANOL (110) ligands and triphenylborate were found to catalyze the asymmetric aziridination efficiently. Good to high yields, excellent enantioselectivities, and cis diastereoselectivities were observed with all the reported substrates, which included aromatic, heteroaromatic and aliphatic imines (Table 1.14). 

Simple aliphatic imines are often considered as being photounreactive. One of the few reported examples of a 1,3-diazetidine formation concerns an imine of difluoroacetone (4.30)433). 

As mentioned in chapter 4.2.3, aliphatic imines are photochemically rather unreactive. When the C—N double bond is conjugated to an electron withdrawing group (e.g. carbonyl group), as in O-alkyl derivatives of succinimide and phthalimide, the reactivity increases and azetidines are obtained in cycloadditions to olefins486). A somehow similar example is the photoaddition of a 6-azauracil derivative to 2,3-dimethyl-2-butene... 

The nature of the substituent directly attached to the N-atom influences the properties (basicity, reduction potential, etc.) of the C = N function more than the substituents at the carbon atom. For example, it was found that Ir-dipho-sphine catalysts that are very active for N-aryl imines are deactivated rapidly when applied for aliphatic imines [7], or that titanocene-based catalysts are active only for N-alkyl imines but not for N-aryl imines [8, 20, 21]. Oximes and other C = N-X compounds show even more pronounced differences in reactivity. 

The more recently reported Zr-catalyzed asymmetric alkylation of aliphatic imines is shown in Scheme 6.18 [58]. Several important principles merit specific mention. (1) The catalytic asymmetric protocol can readily be applied to the synthesis of non-aryl im-... 

Unlike ketones and alkenes, aliphatic imines are reluctant to undergo photoinduced (2 + 2) cycyoadditions. For example, the cyclohexanimines of acetone and its derivatives were studied149. Compound 155 undergoes photoaddition with deuterated acetone, but the oxazetidine 156 decomposes to acetone and hexa-deuterioimine 157 (equation 89). 

Following the cinchonine-catalyzed results, Schaus et al. [46] reported the use of cyclic 1,3-dicarbonyl donors to access adjacent quaternary-tertiary stereogenic centers. Under similar reaction conditions cyclic (l-ketoester and 1,3-diketones afforded the corresponding Mannich adducts in excellent yields and stereoselectivities (Scheme 7). The methodology was also applicable to aryl propenyl imines (32) - a class of novel aliphatic imines. 

Asides from the application of imines on conjugate addition reactions, Deng [87, 88] reported the first asymmetric chiral thiourea catalyzed Friedel-Crafts reaction of indoles with iV-tosyl imines (Scheme 35). The reaction was receptive to various aromatic, heteroaromatic, and aliphatic imines in good yield and high enantioselec-tivity (Scheme 36). 

Two years after the discovery of the first asymmetric Br0nsted acid-catalyzed Friedel-Crafts alkylation, the You group extended this transformation to the use of indoles as heteroaromatic nucleophiles (Scheme 11). iV-Sulfonylated aldimines 28 are activated with the help of catalytic amounts of BINOL phosphate (5)-3k (10 mol%, R = 1-naphthyl) for the reaction with unprotected indoles 29 to provide 3-indolyl amines 30 in good yields (56-94%) together with excellent enantioselec-tivities (58 to >99% ee) [21], Antilla and coworkers demonstrated that A-benzoyl-protected aldimines can be employed as electrophiles for the addition of iV-benzylated indoles with similar efficiencies [22]. Both protocols tolerate several aryl imines and a variety of substituents at the indole moiety. In addition, one example of the use of an aliphatic imine (56%, 58% ee) was presented. 

An extension to aliphatic imines gave a certain level of success. The cyclohexyl-derived precursor 26 was successfully transformed into the corresponding amine 27 in 72% ee (Scheme 2.1.3.8). 

Aliphatic and aromatic aldehydes condense with aliphatic and aromatic primary amines to form JV-substituted imines. The reaction is catalyzed by acids and is generally carried out by refluxing the amine and the carbonyl compound with an azeotroping agent in order to separate the water formed. The aliphatic imines (C5-C10) are obtained in good yield but are unstable and must be used directly after their distillation [2b], Tertiary aliphatic and aromatic aldehydes at room temperature react readily and nearly quantitatively with amines to give the imines without the aid of catalysts [la]. Primary aliphatic aldehydes tend to give polymeric materials with amines as a result of the ease of their aldol condensation [3]. The use of low temperatures and potassium hydroxide favors the formation of the imine product [4a, b]. Secondary aliphatic aldehydes readily form imines with amines with little or no side reactions [5]. 

Although the diastereoselective addition of nucleophiles to imines offers an attractive route to chiral amine derivatives, most chiral nonracemic imines suffer from low reactivity (electrophilicity), resulting in no reaction or competitive reduction with organometallic reagents. Other problems include enolization of aliphatic imines, poor... 

The periluorinated aliphatic imine, periluoro-3-methyl-2-azabut-2-ene is epoxidized using 50 % hydrogen peroxide in alkaline acetonitrile solution to afford 2,3,3-tris(trifluoromethyl)oxa-ziridine in 22% yield (Table 14).236... 

In 1998, Yamamoto et al. reported the first catalytic enantioselective allylation of imines with allyltributylstannane in the presence of a chiral 7i-allylpalladium complex 23 (Scheme 9) [15]. The imines derived from aromatic aldehydes underwent the allylation with high ee values. Unfortunately, the allylation reaction of aliphatic imines resulted in modest enantioselectivities. They proposed that a bis-Jt-allylpalladium complex is a reactive intermediate for the allylation and reacts with imines as a nucleophile. The bis-Jt-allylpalladium complex seemed the most likely candidate for the Stille coupling [16]. Indeed, the Stille coupling reaction takes place in the presence of triphenylphosphine even if imines are present, whereas the allylation of imines occurs in the absence of the phosphine [17]. They suggested the phosphine ligand played a key role in controlling the... 

Catalyst 9 was very effective for the hydrocyanation of both aromatic and aliphatic imines 7 in high enantioselectivities and yields, and either N-benzyl- or N-allylimines could be used. The key elements responsible for the high enantioselectivity were the presence of bulky tert-... 

High anti-diastereoselectivity is observed for several aromatic imines for ortho-substituted aromatic imines the two newly formed stereocenters are created with almost absolute stereocontrol. Aliphatic imines can also be used as substrates and the reaction is readily performed on the gram scale with as little as 0.25 mol% catalyst loading. Furthermore, the Mannich adducts are readily transformed to protected a-hydroxy-/8-amino acids in high yield. The absolute stereochemistry of the Mannich adducts revealed that Et2Zn-linked complex 3 affords Mannich and aldol adducts with the same absolute configuration (2 R). However, the diastereoselectiv-ity of the amino alcohol derivatives is anti, which is opposite to the syn-l,2-diol aldol products. Hence, the electrophiles approach the re face of the zinc enolate in the Mannich reactions and the si face in the aldol reactions. The anti selectivity is... 

Their previous screening of catalysts for of aldol reactions and Robinson annu-lations suggested the possibility that chiral amines might also be able to catalyze the Mannich reaction [30, 31]. Thus, screening of catalysts for Mannich-type reactions between N-OMP-protected aldimines and acetone revealed that chiral diamine salt 10, L-proline 11, and 5,5-dimethylthiazolidine-4-carboxylic acid (DMTC) 12 are catalysts of Mannich-type reactions affording Mannich adducts in moderate yields with 60-88 % ee. To extend the Mannich-type reactions to aliphatic imines, the DMTC 12-catalyzed reactions are performed as one-pot three-component procedures. The o-anisidine component has to be exchanged with p-anisidine for the one-pot reactions to occur. The DMTC 12-catalyzed one-pot three-component direct asymmetric Mannich reactions provide Mannich adducts in moderate yield with 50-86 % ee. 

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