Enantioselective Synthesis of -Amino Sulfones by aza-Michael Addition to Alkenyl Sulfones

Enders, Dieter; Müller, Stephan F.; Raabe, Gerhard

doi:10.1002/(sici)1521-3773(19990115)38:1/2<195::aid-anie195>3.3.co;2-y

Cited by 9 publications

(10 citation statements)

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“…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.…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2012

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Aliphatic polyamines, being a versatile class of organic compounds, are widely used in many fields of medicine and organic chemistry. However, the general approach to the synthesis of chiral aliphatic polyamines has been still undeveloped. Here, we describe a new method for the synthesis of chiral trifunctional amino compounds, namely hydroxydiamines and triamines. The initial compounds, namely substituted hydroxy- or aminopyrazolidines and pyrazolines, are readily available using convenient stereoselective methods developed earlier by us. The proposed method allows synthesizing of chiral diaminoalcohols and triamines, which are the analogs of a well-known anti-TB drug, namely ethambutol, and cannot be obtained alternatively. The key step of the synthesis is N-N bond cleavage in substituted hydroxy- or aminopyrazolidines and pyrazolines with borane-tetrahydrofuran complex; other known methods for N-N bond cleavage turned out to be ineffective. The main advantage of the proposed method is the retention of a certain configuration of stereocenters in the course of the reaction. Six new chiral diasteomerically pure substituted hydroxydiamines and triamines and the enantiomerically pure triamine with four chiral centers were synthesized and characterized using NMR, IR and mass spectroscopy, as well as elemental analysis.

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Section: Resultsmentioning

confidence: 99%

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

et al. 2012

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“…Therefore we tested different Lewis acids [Yb(OTf) 3 , Zn(OTf) 2 , Sn(OTf) 2 , Pr(OTf) 3 , CeCl 3 , Sc(OTf) 3 , SnCl 4 , ZrCl 4 , TiCl 4 , FeCl 3 , MgCl 2 , MgBr 2 , ZnF 2 , ZnBr 2 , Sm(OTf) 3 , LiBr, Cu(OTf) 2 , Eu(OTf) 3 , AgOTf], starting with ytterbium triflate [Yb(OTf) 3 ], which has shown good results in the addition of (S)-1 and (R,R,R)-2 to alkenylsulfones. 20 For our system zinc bromide proved to be the best Lewis acid.…”

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confidence: 82%

Asymmetric Synthesis of β-AminoCyclohexyl Sulfonates, β-Sultams and γ-Sultones

Enders¹,

Wallert²,

Runsink³

2003

Synthesis

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A s y m m e t r i c S y n t h e s i s o f S u l f o n a t e s , b-Sultams a n d g-Sult o n e s Abstract: An efficient asymmetric synthesis of b-aminocyclohexyl sulfonates, b-sultams and g-sultones has been developed. The key step of the synthesis is the Lewis acid catalyzed aza-Michael addition of the enantiopure hydrazines SAMP [(S)-1] or RAMBO [(R,R,R)-2] to alkenylcyclohexyl sulfonates 3. This leads to b-hydrazino sulfonates 4a-k in moderate to good yields (41-85%) and diastereomeric excesses (de = 44-90%). The epimers were separated by preparative HPLC. Subsequent reductive N-N bond cleavage with BH 3 ·THF and protection of the resulting amines with CbzCl gave N-Cbz-protected b-aminocyclohexyl sulfonates 6a-k in moderate to good yields (38-68% over 2 steps) and high enantiomeric excesses (ee ³ 96%). a-Alkylation of 6 with various electrophiles afforded a-alkyl-b-aminocyclohexyl sulfonates 10a-g in good to excellent yields (67-92%) and moderate to high diastereomeric excesses (de = 71-93%). After alkylation with allyl iodide, the first asymmetric iodosultonization was achieved with high selectivities. Compounds 6g-k were also cyclized in a four-step synthesis to highly enantio-enriched 3-substituted-1,2-thiazetidine 1,1-dioxides (b-sultams) 9a-e.There is constant need for the synthesis of unnatural amino acids, since these compounds can provide new biological activities and their peptides are attractive targets for drug discovery. The best-known b-aminosulfonic acid is taurine, which is important for the evolution of the central nervous system of many mammals. Moreover, derivatives like 2-amino-2-phenylethanesulfonic acid, 1 a potential GABA B receptor antagonist or flavocristamides A and B, 2 which have inhibitory activity against DNA polymerase a, demonstrate the demanding interest for the asymmetric synthesis of taurine derivatives. Furthermore, the exchange of a-or b-amino acids in peptides for b-aminosulfonic acids or the synthesis of b-sulfonopeptides have drawn great attention. 3 White et al. designed b-sulfonopeptides as inhibitors of D-alanyl-Dalanine transpeptidase containing taurine instead of a penultimate amino acid. 4 Liskamp et al. synthesized oligo-petido sulfonamides on solid-phase starting from a-amino acids in order to analyze their secondary and tertiary structure as well as their biological activity. 5As we have described in a previous communication, the aza-Michael addition provides an efficient access to taurine derivatives. 6 As shown in Scheme 1, the reaction starts with 1,4-addition of enantiopure nitrogen nucleophiles to alkenyl sulfonates, followed by cleavage of the chiral auxilaries. This leads to chiral b-amino sulfonates, which can be used in the synthesis of 3-substituted 1,2-thiazetidine 1,1-dioxides (b-sultams) and g-sultones.Scheme 1 Asymmetric synthesis of b-aminocyclohexyl sulfonates, g-sultones and b-sultams by aza-Michael addition b-Sultams are the sulfonyl analogues of b-lactams. Therefore, they are interesting building blocks for the synthesis of new antibiotics, corre...

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“…16 Subsequent N-N bond cleavage of the resulting β-hydrazino sulphones 1 leads to enantiomerically pure protected amines 6. The employment of Raney-nickel is not feasible, since the C-S bond is cleaved under these reaction conditions.…”

Section: Methodsmentioning

confidence: 99%

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

Enders¹,

Lochtman²,

Meiers³

et al. 1998

Synlett

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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 ...

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Enantioselective Synthesis of -Amino Sulfones by aza-Michael Addition to Alkenyl Sulfones

Cited by 9 publications

References 10 publications

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

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

Asymmetric Synthesis of β-AminoCyclohexyl Sulfonates, β-Sultams and γ-Sultones

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

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Enantioselective Synthesis of -Amino Sulfones by aza-Michael Addition to Alkenyl Sulfones

Cited by 9 publications

References 10 publications

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

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

Asymmetric Synthesis of β-AminoCyclohexyl Sulfonates, β-Sultams and γ-Sultones

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

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