Reductive amination strategy

These results are outstanding when considering that a reductive amination strategy has been employed and are even more impressive because aliphatic ketones, which are historically avoided because of poor yield and ee, are also acceptable... 

Scheme 7.8 Application of aldol/reduction amination strategy formal synthesis of lopin...

Brooks, P.R. Caron, S. Coe, J.W., et al. Synthesis of 2,3,4,5-tetrahydro-l,5-methano-lh-3-benza-zepine via oxidative cleavage and reductive amination strategies. Synthesis 2004, 11, 1755-1758. 

Tojima, T., Katsura, H., Han, S. M. et al. 1998. Preparation of an a-cyclodextrin-linked chitosan derivative via reductive amination strategy. J. Polym. Sci. Part A Polym. Chem. 36 1965-1968. 

Yao et al. reported a chemo- and stereoselective asymmetric total synthesis of (-)-lannotinidine B 179 through two reductive amination in a domino fashion. Thus, the tricarbonyl compound 175 was treated with benzylamine in the presence of NaBH(OAc)3 to give 178 via 176 and 177 (Scheme 9.30) [90]. Similar reductive amination strategies have been apphed for several other natural products [22a]. 

However, due to the fact that the strategy outlined in Scheme 47 is limited to the generation of 5-nitro-substituted benzotriazoles 332, a different access to o-amino-substituted triazenes was sought. Starting from o-nitro triazenes 335, reduction under newly developed conditions (Zimmermann et aL, 2007, personal communication) suitable for acid sensitive linkers gave access to the o-amino-substituted resins. Consequently, a reductive-amination strategy was also viable, fii this case, 3-alkylmethyl or 3-arylmethyl benzotriazoles 338 are accessible in good yields (Scheme 48). 

Synthesis of Pyrrolidine and Indolizidine Alkaloids via Reductive Amination Renaud and coworkers developed a method for a one-pot azide reduction/ intramolecular reductive amination strategy.This methodology opened up a new route for the synthesis of a variety of pyrrolidine and indolizidine cores. 

Show how each of the following compounds could be prepared using a reductive amination strategy ... 

One route is by reductive amination of ketone (10) available by Friedel-Crafts reaction from acid (11) which we can make by an FGA strategy (Chapter T 24). 

The hydroformylation reaction strategy has recently been extended, in a novel way, to the manufacture of primary amines by hydroaminomethylation of olefins with ammonia in a two-phase system. Thus, 1-pentene was reacted with ammonia here hydroformylation to an aldehyde, with CO and H2, with subsequent reductive amination occurs in a domino reaction. The catalyst was Rh/Ir/TPPS (Zimmermann et al., 1999). 

A reductive amination/cyclization strategy was used by Surya Prakash Rao and coworkers to synthesize the annulated tricyclic compounds 10-93 [34]. These authors employed the microwave irradiation of a cis/trans- mixture of 1,5,9-triketone 10-92 with an excess of ammonium formate for 1 min in 87 % yield (Scheme 10.23). 

The described fluorous-tag strategy has also been applied to the synthesis of biaryl-substituted hydantoins (Scheme 7.81) [94]. 4-Hydroxybenzaldehyde was converted into the corresponding perfluorinated species, which was then subjected to a reductive amination. The resulting amine was treated with an isocyanate to produce the fluorous-tagged urea, which spontaneously cyclized to form the corresponding hydantoin. Finally, the fluorous tag was detached by a Suzuki-type carbon-carbon bond formation to furnish the desired target structure in good yield. 

An ingenious strategy developed by Jun s group makes use of a chelating 3-picolin-2-yl group for performing C-C bond forming reactions. In the particular example shown, for the synthesis of aromatic ketones, methylvinyl ketone is added to suppress unwanted reductive amination processes (Equation (130)). 

Synthesis of a C(8)-C(18) segment of the larger fragment of lb using the same basic strategy is depicted in Scheme 25. Here, hydroxy ketone 176 was subjected to syn-selective (dr of crude product=90 10) reductive amination [42] with sodium cyanoborohydride and benzylamine followed by tetrahydro-oxazine formation using aqueous formaldehyde. The resulting heterocycle 182 was then converted to unsaturated ester 184 by successive desilylation, oxidation, and entirely (Z)-selective Horner-Wadsworth-Emmons olefination. Re-... 

The spacer arm length between the hapten and the carrier is in the range of 6 to 8 A, which should eliminate any steric interference with carrier side chains. According to the protocol described by Schultz the haptens were coupled to BSA and KLH via A-(3-dimethylaminopropyl)-A -ethylcarbodiimide or the N-hydroxysuccinimide ester at pH 5.5 in water. Other coupling strategies include substitution with diazonium salts and reductive amination. The ratio of hapten-carrier range between 8 and 15 haptens per carrier. 

In the enzymatic part of the process, a one-pot conversion was achieved by using Candida lipase (Lip) to hydrolyze the ester and then LeuDH to catalyze the reductive amination (with or without N labeling). In this case, the coenzyme recycling was accomplished by adding FDH and formate. The same group used a similar enzymatic strategy to prepare labeled L-threonine and L-allothreonine starting from the a-keto methyl ester. ... 

Scheme 4.10 General strategy for the chemoenzymatic synthesis of iminocyclitols based in the use of aldolases and palladium-mediated reductive amination.

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