Ketimines protection

Addition of phosphonylated Schiff base to ethyl acrylate, under phase-transfer catalytic conditions in the presence of Aliquat 336 and KOH at room temperature, leads to the 1 1 Michael adduct with 60% yield (Scheme 8.57). The tert-butyl and ketimine protecting groups are eliminated under mild conditions (1 M HCl, room temperature) to provide the phosphonic analogue of glutamic acid. 

Optically pure a-amino acids can be converted to 1,2-diamines by a route that involves the preliminary formation of N-protected a-aminonitriles through the intermediate amides. The addition of organometallic reagents to these a-aminonitriles gives a-amino ketimines, which are then reduced in situ to 1,2-diamines. However, this route has been scarcely applied to acychc a-aminonitriles. As a matter of fact, the sequential addition of methylmag-... 

As an alternative to oxidative deamination, decarboxylation is involved in polyamine biosynthesis and in the protection of enteric bacteria from acidic conditions. Under these conditions, the electrons used to form the ketimine are provided by decarboxylation in place of those from the a-methine group. 

Protection of the nitrogen in 4 faced the classical N- versus O-alkylation selectivity issue, which was solved by selection of the solvent system. The original protecting group, pMB, was replaced with 9-anthrylmethyl (ANM), which provided the best enantioselectivity with the newly discovered asymmetric addition to the ketimine. 

Taking Tomioka s pioneering work [8] as a precedent, we have screened 13-amino alcohols as chiral modifiers [9] in the nucleophilic addition of lithium 2-pyridinylacetylide 6 to the pMB protected ketimine 5. We were pleased to discover that when 5 was treated with a mixture prepared from 1.07 equiv each of quinine and 2-ethynylpyridine by addition of 2.13 equiv of n-BuLi in THF at -40 to -20 °C, the desired adduct 19 was obtained in 84% yield with maximum 64% ee. Soon after, we found selection of the nitrogen protective group had great influence on the outcome of the asymmetric addition and the ANM (9-anthranylmethyl)... 

Table 1.2 Asymmetric addition of 2-pyridiylacetylide to pMB protected ketimine 5.

This tertiary amide-functionalized Schiff base thiourea was found to efficiently catalyze the asymmetric Strecker reaction [157] of N-benzyl-protected aldimines and also one ketimine in high enantioselectivities (86-99% ee) and proved superior to 42 examined under the same conditions (1 mol% loading, toluene, -78 °C, HCN) (Scheme 6.46) [198]. 

The possibility of employing a wide range of nucleophilic radical sources, including alcohols, the choice of ideal protecting groups for amines, and the possibility of extending this process to ketimines by the development of a catalytic system in which TiCLt is associated with Zn, enables us to anticipate new frontiers for the synthesis of new structural types of a-amino acids and other amino-derivatives of crucial importance for chemistry, medicine, and life. 

In 2005, both Rueping et al. and List et al. reported the first transfer hydrogenation with Hantzsch ester 1 of several N-protected ketimines catalyzed by chiral Bronsted acids derived from l,l -binaphthol [17, 18]. The reaction typically requires 1 to 20 mol% of catalyst, is performed in benzene at 60 °C, and enantio-selectivities of up to 90% are obtained. The chiral Bronsted acid protonates the lcetimine at nitrogen, giving an ion-pair which is reduced by Hantzsch ester 1. (For experimental details see Chapter 14.21.2). A preferred transition state has... 

Cyclopropylideneamines were trapped in an intramolecular manner during the Favorskii rearrangement of suitably functionalized a-chloro ketimines 44 bearing a protected nucleophile in the molecule. Base-induced 1,3-dehydrochlorination generates the three-membered ring intermediate 45 which undergoes intramolecular nucleophilic addition of the deprotected nucleophile to form adducts 46. 

On the other hand, the Chi group reported NHC-catalyzed homoeno-late additions of a,p-unsaturated aldehydes to isatin-derived Boc-protected ketimines to afford spirocyclic oxindole-y-lactams with high diastereo- and enantioselectivity (up to 83% yield, 99% ee, and 20 1 dr) (Scheme 7.49). ... 

Chitosan is a multi-nucleophilic polymer due to the presence of the NH2 and OH functional groups. The initial sites where substitution occurs are the more nucleophilic amino groups. However, the experimental conditions and protection of the NH2 groups reduces the intermolecular hydrogen bonding and creates space for water molecules to fill in and solvate the hydrophilic groups of the polymer backbone (Sashiwa and Shigemasa 1999). A -alkylated derivatives can be obtained by the treatment of chitosan with aldehydes or ketones via formation of Schiff base intermediates, aldimines (from reactions with aldehydes), or ketimines (from reactions with ketones) followed by reduction of the imine with sodium borohydride. 

The diastereo-selective synthesis of protected CM-2-aminocyclopropanols has been performed by the reaction of A-f-butylsulfinyl ketimines with acylsilanes. A cascade transformation involving the formation of two carbon-carbon bonds and an oxygen-silicon bond is a key feature of this reaction. 

Scheme 6.19 Rhodium-catalyzed arylation of N-protected ketimines, as described by Hayashi s group [24],...

Since there is great interest in compounds bearing quaternary stereocenters, soluble catalyst 25 was also applied to keto-imines in the presence of in situ generated HCN (Scheme 30.6) [17]. Whereas hydrocyanation adducts of N-allyl protected ketimines were prone to decompose via a retro-Strecker reaction, N-benzylated Strecker adducts 28 were obtained in mostly excellent yields and very high ee s. In general, acetophenone imines 27 were suitable substrates whereas aliphatic ketimines 27 showed a lowered optical purity. Although the benzyl protection group was necessary to obtain stable Strecker adducts 28, transformation of these adducts into amino acids was made more difficult. It could also be shown that... 

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