Chiral ligands containing heteroatoms. III. Enantioselective ketone reductions using tin(II) organometallic systems from chiral piperazines (original) (raw)
Related papers
Tetrahedron: Asymmetry, 1993
Starting from enantiomerically pure serine, a series of (2R,5S) and (2S,5S)-2hydroxymethyl-5-alkyl piperazines l-5 were prepared in good yields without any racemization. The use of these compounds as chiral catalysts for the enantioselective addition of diethylzinc to aldebydes is described. This paper reports the first example of the use of piperazine methanols in asymmetric synthesis. Catalytic enantioselective carbon-carbon bond forming is now recognised as one of the most important problems in organic synthesis.2 It is known that enantioselective addition of organometallic reagents to aldehydes in the presence of amino alcohols affords optically active secondary alcohols.3 Recently. in our laboratory, we found that amino pyridines also act as chiral catalysts in the enantioselective addition of diethylzinc to aldehydes. 1 T4 There are only a few examples reported, in which, optically active piperazines have been used as chiral modifiers in asymmetric reactions.5 Although C2-symmetric piperazines having an o-hydroxyphenyl substituent have been reported,sc this study represents the first example of the use of piperazine methanols in the enantioselective addition of diethylzinc to benzaldehyde. We wish to report the synthesis of (2R.5.Y) and (2.$5s)-2-hydroxyme.thyl-5-alkyl piperazines l-5 and a detailed study of the dialkylzinc-henzaldehyde addition carried out by using compounds l-5 as chirsl catalysts. The piperazines l-5 were prepared according Scheme I+ commercial amino acids were converted into the corresponding N-benzyloxycarbonyl derivatives la-5a that were Ueated with (s) or (R) H-Ser-OMeHCl to give dipeptides lb-Sb using the mixed anhydride coupling method. Deblocking the benzyloxycarbonyl group was carried by transfer hydrogenation (10% of any volatile in dry methanol to previously reported diketopiperazines
Novel chiral N,N′-dimethyl-1,4-piperazines with metal binding abilities
Tetrahedron, 2015
With the objective of developing novel chiral ligands, we report an efficient strategy to prepare chiral N,N-dimethyl-1,4-piperazines, six-member heterocyclic molecules that possess metal binding features. We prepared and characterized 18 piperazines, and evaluated their ability to complex different monoand divalent metals, using a rapid picrate extraction technique. Some newly prepared diamine ligands were used in diethylzinc alkylation of aryl aldehydes. Yields increased significantly in the presence of the diamine ligands, though enantioselectivity was low. The results demonstrate the validity of the approach for preparing and identifying useful chiral diamine ligands.
The Journal of Organic Chemistry, 1999
A family of enantiomerically pure (4R,5R)-2-alkyl-4-phenyl-5-(R-oxymethyl)-1,3,2-oxazaborolidines (5) [boron substituent: H, CH 3 , n-C 4 H 9 ; R-oxy group: CH 3 O, CH 3 OCH 2 CH 2 O, CH 3 (OCH 2 CH 2 ) 2 O, PhCH 2 O, Ph 2 CHO, Ph 3 CO] has been prepared from (2S,3S)-2,3-epoxy-3-phenylpropanol (2) through a four-step sequence involving protection of the alcohol, regioselective ring-opening of the epoxide with sodium azide in acetonitrile in the presence of LiClO 4 , reduction of the azido group (H 2 /Pd-C/MeOH or NaBH 4 /THF-MeOH), and formation of the oxazaborolidine ring with the appropriate boron reagent. Both the boron substituent and the R-oxy group have been optimized for maximal enantioselectivity in the reduction of prochiral ketones with borane. The optimal oxazaborolidine (5a-Me) [boron substituent: CH 3 ; R-oxy group: CH 3 O] has been employed (10% molar amount, THF, 0°C to room temperature) in the reduction of a representative family of 10 substrates comprising alkyl aryl ketones and dialkyl ketones. In these reductions, 5a-Me induces the formation of secondary alcohols of S configuration with high enantioselectivity (93% mean enantiomeric excess). The origin of the enantioselectivity in the reduction has been rationalized by means of semiempirical AM1 calculations. .
Tetrahedron Letters, 2007
Reduction of (1R,6R)-7,9-diazabicyclo[4.2.2]dec-3-ene-8,10-dione (5) with lithium aluminum hydride gave a mixture of the expected (1R,6R)-7,9-diazabicyclo[4.2.2]dec-3-ene (2) as well as 7,9-diazabicyclo[4.3.1]dec-3-ene , resulting from 1,2-r (C-C) migration of the pendant cis-2-butenyl ring. More of the rearranged product was observed in polar solvents and upon the addition of HMPA. The relief of ring strain imparted by the olefin may promote this rearrangement, as it was not observed when the olefin was reduced prior to the reduction.
Regio- and Stereodivergent Allylic Reductions of Bicyclic Piperidine Enecarbamate Derivatives
The Journal of Organic Chemistry, 2018
The particular nature of tetrahydropyrido[4,3-e]-1,4,2-dioxazines of type 1 allows the regio-and stereoselective obtainment of substituted N-carbamoyl tetrahydropyridines by common reducing agents. A completely novel, biologically active, bicyclic 1,3-diaza-4-oxa-[3.3.1]-nonene scaffold can be generated by the use of lithium triethylborohydride through an unprecedented cascade syn-SN2' reduction/carbamate reduction/cyclization reactions. The remarkable regioselectivity switches of allylic reduction process have been rationalized with the aid of computational studies. Tetrahydropyridines are important targets in synthetic organic chemistry due to their relevance as privilege structure in medicinal chemistry. 1 Therefore, considerable efforts have been devoted to the individuation of new methods for their regio-and stereoselective synthesis and functionalization. 2 However, a regio-and stereodivergent reduction of piperidine enecarbamates bearing an allylic leaving group has not yet been reported. The main reason for this shortcoming can be found in the relative instability of 1,2,3,4tetrahydropyridine derivatives containing common leaving groups at the C4-position. We recently became interested in the elaboration of nitroso cycloadducts derived from 2substituted-1,2-dihydropyridines, 3 easily accessible by addition of nucleophiles to activated pyridinium salts (eq. a, Scheme 1). 4,5 The [3,3]-hetero Cope rearrangement of the obtained nitroso Diels-Alder (NDA) cycloadducts has been reported to give 4a,7,8,8atetrahydropyrido[4,3-e]-1,4,2-dioxazines of type 1 (eq. a, Scheme 1). 6 We noticed that the study of their reactivity is limited to the NO reductive cleavage with Raney nickel to obtain racemic aminoarabinose and aminoaltrose derivatives. 6a On the other hand, palladiumcatalyzed allylic reduction have been used extensively in synthetic organic chemistry to
A new method for the preparation of unsymmetrical 1,4-substituted piperazine derivatives
Tetrahedron-asymmetry, 1999
Symmetrical and unsymmetrical N,N -piperazine derivatives of (−)-norephedrine and o-aminophenol were synthesized stereoselectively in yields >70% by reduction of the corresponding N,N -ethylenebisoxazolidine heterocycles. The stereochemistry at the ring fusion carbons was established by NMR spectroscopy and X-ray crystallography.
Tetrahedron: Asymmetry, 1994
The asymmetric reduction of pro&al ketones to chiil secondary alcohols by LiilJ& modified with optically active diethanolamines, was studied. Asymmetric inductions of up to 94% were obtained with these reagents. The stereoselectivity of the reaction was found to depend both upon the temperature at which the reduction was performed and upon the conditions under which the chiral aluminum hydride reagent had been prepared. By changing the substituents at the carbon atom a to nitrogen in the chiral auxiliary, either the (R)or the (S)-enantiomer of the secondary alcohol could be obtained in excess. Recently, we have prepared a series of optically active diethanolamines, having two, three, or four stereogenic centers in the diethanolamine backbone. These were used as chiral building blocks in the synthesis of dim-crown ethers.6 The synthetic route followed allowed systematic variation of the substitution pattern. We now report the asymmetric reduction of prochiral ketones, using LiAlH, modified with chiral diethanolamines 6a-d. These diethanolamines possess a G-axis of symmetry and differ only in the substituents attached to the carbon atoms a to nitrogen. Systematic variation of these substituents was expected to provide valuable information about the nature of the transition state of the reduction reaction. RESULTS and DISCUSSION Chiial O-protected diethanolamines 5a-d were prepared from optically active O-protected cyanohydrin 1' via a one-pot Grignani-transimination-reduction' or a one-pot reduction-transimination-reduction9 procedure, as previously reported.6 Thus, 1 was treated with a Grignard reagent or with DIBALH to form an imine-metal complex (Scheme I). Dry methanol was added to protonate the imine anion and to destmy the excess of Grignard reagent or DIBALH. Upon addition of an excess of
Tetrahedron, 1994
An improved synthesis of 2-(T-pyridyl)-2-aminoalcohols la and lb, in enantiomerically pore form via 1,3-oxazolidine derivatives is presented. Some efficient and selective methods for both the cleavage of the oxazolidine ring and the removal of the N-Boc px%ecting group are also mported. Optically active amiuo alcohols are of relevance as tools in asymmetric processes.2J~4 Very recently we have reported the preparation of (R)-2-amino-2-(2'-pyridyl)ethan-l-01 (la) and (lR,2R)-l-amino-l-Q'pyridyl)propan-2-01 (lb) starting from natural L-serine and L-threonine by means of a multistep reaction sequence, in ca. 25 % overall yield.1 H2 H2 la lb In the context of a project designed to use these compounds in asymmetric reactions, such as the alkylation of aldehydes with dialkylzinc reagents.3 the reduction of ketones to alcohols with boranes4 and for the preparation of bis ox-line derivatives with C2 axial symmetry? we required au efficient route to prepare multigram quantities of both la and lb. In this paper we wish to describe a very simple preparation of N-tbutoxycarbonyl-or N-benzoyl-protected 4-(2'~pyridyl)-1,3-oxazolidines 5a-c as versatile precursors of la and lb. Efficient procedures for the selective removal of the N-protecting groups are also reported. Compounds lab were achieved through a five step reaction sequence (Scheme 1) with 60% overall yield without loss of enantiomeric excess. Q-N-Benzoyl-1.3-oxazolidine-4-carboxylic acid (2b) was obtained as previously described for the D enantiomer.6 Through a simple modification, (S)-N-t-butoxycarbonyl-1,3-oxazolidine4carboxylic acid (20) and (4S,5R)-N-t-butoxyc~~nyl-5-~~yl-1,3-oxazolidine-4-c~xylic acid (2~) were obtained by reaction of L-serine or L-threonine with formaldehyde (aq 37%. NaOH 2N), followed by trapping with Boc20 up to 250 mm01 scale, in a facile one pot reaction (Scheme 1).