Efficient N-N Bond Cleavage of Chiral Trisubstituted Hydrazines with BH₃ ⋅ THF

Abstract

Cleavage of the N-N bond of chiral trisubstituted hydrazines 1 with excess BH 3 ⋅THF complex gives the corresponding optically active amines 2 in moderate to excellent yields and with high enantiomeric purity. This racemization and epimerization free cleavage procedure is compatible with functionalities sensitive to reductive cleavage conditions.Enantiomerically-pure amines are fundamental structures and of great importance in organic synthesis. We have recently reported an efficient asymmetric synthesis of optically active amines based on the SAMP/ RAMP-hydrazone methodology. 1 Conversion of aldehydes into SAMP/ RAMP-hydrazones and subsequent 1,2-addition of organometallic compounds leads to the corresponding hydrazines 1. 2 Alternatively, β-acceptor substituted hydrazine derivatives 1 can be synthesized diastereoselectively via conjugate addition of an enantiopure nitrogen nucleophile such as SAMP to enoates or 1-alkenyl sulphones. A key step in all these procedures to prepare optically active amines 2 is the cleavage of the hydrazine N-N bond.We now wish to report an efficient method using BH 3 ⋅THF as a cleavage reagent for trisubstituted hydrazines 1 in order to access the amines 2, such as (1-ferrocenylalkyl)amines 3, 1,1′-bis(1-amino-alkyl)-ferrocene derivatives 4, 1,2-diamines 5, β-amino sulphones 6 and BH 3 -protected β-amino phosphines 7 (Scheme 1, Figure 1). Scheme 1Several methods for the cleavage of hydrazine N-N bonds have been reported in the literature. The reductive cleavage of heteroatomheteroatom bonds using samarium (II) iodide is well known. 3 Lithium 4 and sodium 5 in ammonia has been used to cleave hydrazines, which have been activated by prior conversion to acetyl or benzoyl derivatives. However, this procedure suffers from occasional undesired cleavage of the C-N bond instead of the N-N bond. Several groups have also reported hydrogenolytic N-N bond cleavage methods using platinum dioxide, 6 palladium hydroxide 7 or palladium on carbon 8,3d as catalysts. An additional well-known catalytic method is the Raney-nickel promoted hydrogenolysis of hydrazine N-N bonds. 9 In this case the cleavage reaction is dependent on the activity of the catalyst, which can be deactivated in several steps due to the preparation procedure. 10 Unfortunately, this N-N bond cleavage protocol suffers from harsh reaction conditions, a tedious preparation, competitive hydrogenation of aromatic residues and partial racemization and epimerization. Zinc in acetic acid 11 and formic acid 12 are other reagents to cleave hydrazine N-N bonds.Feuer and Brown 13a observed during their investigations to reduce the carbonyl groups of 1,2-dialkylperhydropyridazine-3,6-diones that a large excess of BH 3 ⋅THF resulted in N-N bond cleavage. However, BH 3 ⋅THF could only be applied to tetrasubstituted hydrazines, with the cleavage of trisubstituted hydrazines being unsuccessful. Kibayashi et al. 13b-e have also published a similar method for the cleavage of tetrasubstituted hydrazines.We now wish to report our method to cleave N-N ...

Intramolecular Hydride Transfer Reactions in (Formazanate)Boron Dihydride Complexes

“…These data suggest that also the transformation from 3a to 4a is a first-order reaction, with a rate constant of 0.009 min −1 at 130 °C. While cleavage of N−N bonds has been reported using a variety of metal-based reducing agents 19 as well as BH 3 •THF, 20 the formation of N−N cleavage product 4 is remarkable because it occurs intramolecularly. On the basis of analogy with the N−N cleavage that is observed upon 2e-reduction of the boron difluoride analogue, 13 we speculate that a related reductive cleavage takes place in the conversion of 3 to 4.…”

Synthesis of hydroxydiamines and triamines via reductive cleavage of N–N bond in substituted pyrazolidines

“…The convenient way of synthesis of the starting compounds in diasteriomerically pure forms had been developed by us earlier (Sviridova et al 2008;Tavtorkin et al 2009). All aforementioned reductive methods were tested for the preparation of polyamines; however, the satisfactory results were obtained only for the borane-tetrahydrofuran complex (Feuer and Brown 1970;Enders et al 1998Enders et al , 1999. This reagent not only reduced N-acetyl group, but also splitted N-N bond in a heterocycle, giving rise to polyamines in the form of boron-containing complexes.…”

Strategy for the Synthesis of Polymeric Supports with Hydrazone Linkers for Solid-Phase Alkylation of Ketones and Aldehydes

“…Now the alkylated ketone or aldehyde hydrazones could be either cleaved with trifluoroacetic acid to provide carbonyl compounds or subjected to specific cleavage/workup manipulations. Thus, oxidative protocols applied to aldehyde hydrazones provide nitriles (m-CPBA) and carboxylic acids (e.g., hydrogen peroxide) while reductive cleavage with borane−THF or reductive postcleavage workup (e.g., sodium borohydride) gave primary amines and alcohols, respectively (Scheme ).

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