Vitali Tararov

A Scrutiny on the Reductive Amination of Carbonyl Compounds Catalyzed by Homogeneous Rh(I) Diphosphane Complexes

The reductive amination of a series of aldehydes with secondary amines and H2 in the presence of a homogeneous Rh-diphosphane catalyst was studied in order to establish a general mechanism of this reaction and to identify conditions for the improvement of the amine/alcohol ratio in the product. Several possible intermediates as constitu- ents of changing equilibria like half-aminals, N,O- acetals and aminals were observed in the reaction mixture by means of 1 H NMR spectroscopy. In individual trials, these compounds could be success- fully hydrogenated under the conditions applied for reductive amination (50 bar H2 pressure, MeOH). Some evidence is accumulated that half-aminals and N,O-acetals might be key intermediates of the reductive amination. Moreover, it was found that the formation of the undesired product alcohol is likely based on the reduction of the startingcarbonyl compound. However, due to numerous equilibria consistingof several intermediates, g conclu- sions are hard to be drawn. Proof will be given that, in several cases, the efficiency of the reductive amina- tion of aliphatic aldehydes can be significantly improved by prehydrogenation of the cationic (Rh(dppb)(COD)) complex.

Economic preparation of 1,3-diphenyl-1,3-bis(diphenylphosphino)propane: a versatile chiral diphosphine ligand for enantioselective hydrogenations

Abstract The enantioselective hydrogenation of 1,3-diarylpropane-1,3-diones with chiral Ru(II)-diphosphine catalyst has been studied. In a first approach it was found, that Tol-BINAP together with Ru(COD)methallyl 2 formed the most selective catalyst. One of the C 2 -symmetric enantiopure 1,3-diols obtained in turn was transformed via its 1,3-di- O -mesylate into 1,3-bisdiarylphosphines. One of them, 1,3-diphenyl-1,3-bis(diphenylphosphino)propane, could be advantageously utilized as a ligand for the efficient enantioselective Ru-catalyzed hydrogenation of its own 1,3-diketone precursor. Thus, the condition for a ‘cross self-breeding’ catalytic system is fulfilled. A further reduction of the preparation costs could be achived by application of RuCl 3 ·H 2 O instead of other more expensive precatalyst precursors without compromosing the enantioselectivity. The ligand was used in the Rh(I)-catalyzed asymmetric hydrogenation of model substrates and β-amino acid precursors where up to 97% ee could be achieved.

Highly stereoselective hydrogenations—As key-steps in the total synthesis of statins

Statins are inhibitors of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMG-CoA reductase) and became the standard of care for treatment of hypercholesterolemia because of their efficacy, safety, and long-term benefits. They are administered as diastereo- and enantiomerically pure compounds. We summarize here two new approaches for the total synthesis of the most important representatives, atorvastatin, and rosuvastatin, based on highly stereoselective hydrogenations as key-steps.

Chemical modification of the plant isoprenoid cytokinin N6-isopentenyladenosine yields a selective inhibitor of human enterovirus 71 replication

In this study, we demonstrate that N(6)-isopentenyladenosine, which essentially is a plant cytokinin-like compound, exerts a potent and selective antiviral effect on the replication of human enterovirus 71 with an EC50 of 1.0 ± 0.2 μM and a selectivity index (SI) of 5.7. The synthesis of analogs with modification of the N(6)-position did not result in a lower EC50 value. However, in particular with the synthesis of N(6)-(5-hexene-2-yne-1-yl)adenosine (EC50 = 4.3 ± 1.5 μM), the selectivity index was significantly increased: because of a reduction in the adverse effect of this compound on the host cells, an SI > 101 could be calculated. With this study, we for the first time provide proof that a compound class that is based on the plant cytokinin skeleton offers an interesting starting point for the development of novel antivirals against mammalian viruses, in the present context in particular against enterovirus 71.

Facile Preparation and Purification of Mono tert‐Butyl Malonate

Abstract Reaction of Meldrums acid with tert‐BuOH gives tert‐BuO2CCH2CO2H, which can be easily purified via its corresponding crystalline ammonium salt and subsequent acidification.

FACILE SYNTHESIS OF 8-AZIDO-6-BENZYLAMINOPURINE

Bromination of 6-benzylaminopurine (1) with Br2 in AcOH in the presence of AcONa afforded 6-benzylamino-8-bromopurine (2) in 59% yield. The position of bromination was confirmed by direct transformation of bromide 2 by reaction with NaN3 in dimethyl sulfoxide to 8-azido-6-benzylaminopurine (3) in a yield of 70% and comparison of its properties with the known compound 2-azido-6-benzylaminopurine (11). Compounds 3 and 11 were checked for their biological activity in specific biotests based on the primary cytokinin effects in living plants. Both synthesized compounds displayed effects similar to the typical cytokinin 6-benzylaminopurine (1).

HOMOGENEOUS RHODIUM(I)-CATALYZED REDUCTIVE AMINATIONS

INTRODUCTION ...................................................................................................................... 101 I . HYDROGENATION OF UNSATURATED AND SATURATED NITROGEN SUBSTRATES ................................................................................................. 103 1 . Hydrogenation oflmines ................................................................................................. 103 a) General Aspects ............................................................................................................. 103 b) Enantioselective Hydrogenation of Imines ................................................................... 103 2 . Enantioselective Hydrogenation of Enamines ............................................................... 105 3 . Homogeneous Catalyzed Cleavage of N, 0-Acetuls and Related Compounds .............. 107 a) General Aspects ............................................................................................................. 107 b) Hydrogenation of 1, 3-Oxazolidines .............................................................................. 108 i ) General Aspects .......................................................................................................... 108 i i ) Kinetic Resolution of Racemic 1. 3-Oxazolidines .................................................... 109 11 . DIRECT REDUCTIVE AMINATION @RA) OF CARBONYL COMPOUNDS ....... 111 1)GeneralAspec ts ................................................................................................................. 111 2) Concerning the Formation of the Undesired Akohol .................................................... 114 3) Enantioselective Reductive Amination ............................................................................ 115 111 . COMPARISON OF HYDROGENATION OF INTERMEDIATES (IRA) WITH DIRECT REDUCTIVE AMINATION @RA) ................................................................ 117 REFERENCES ............................................................................................................................ 117

Synthesis of N6‐Substituted Adenosines as Cytokinin Nucleosides

This unit describes preparation of N6‐substituted adenosines (cytokinin nucleosides), a unique class of compounds with a wide spectrum of biological activities. Regioselective alkylation of N6‐acetyl‐2′,3′,5′‐tri‐O‐acetyladenosine with alkyl halides under basic conditions or alcohols under Mitsunobu conditions followed by deprotection are the methods of choice for the preparation of the cytokinin nucleosides. The attractive feature of this strategy is the possibility of using a broad library of commercially available alkyl halides and alcohols under mild reaction conditions.