Synthesis of diastereoisomeric 6-deoxy-d-allal- and 6-deoxy-d-galactal-derived allyl epoxides and examination of the regio- and stereoselectivity in nucleophilic addition reactions. Comparison with the corresponding 6-O-functionalized allyl epoxides

The new 6-deoxy-d-allal- and 6-deoxy-d-galactal-derived allyl epoxides 8α and 8β have been stereoselectively prepared and their behaviour as glycosyl donors in addition reactions with nucleophiles examined and compared with that of the corresponding 6-OR (R=Bn, Tr) substituted epoxides. The completely stereoselective substrate-dependent glycosylation process found in the reaction of 8α and 8β with O-nucleophiles (alcohols and partially protected monosaccharides) and C-nucleophiles (alkyl lithium compounds and TMSCN), indicated that a 6-OR group in the side chain is not necessary for determining the selectivity. The reaction of 8α and 8β with azide (TMSN₃, N-nucleophile) made it possible to revise a previously proposed rationalization for the formation of the corresponding cis-azido alcohol (syn-1,2-addition product).     

Lipase-catalyzed desymmetrization of meso-1,2-diaryl-1,2-diaminoethanes

The synthesis and enzyme-catalyzed desymmetrization of meso-1,2-diaryl-1,2-diaminoethanes have been investigated. A family of aromatic meso-1,2-diamines, containing different substitution patterns in the aromatic ring, was first prepared and then desymmetrized enantioselectively using lipases as biocatalysts. Selective alkoxycarbonylation of one of the amino groups was achieved using allyl carbonates, isolating the corresponding allyl monocarbamates with moderate to high enantiomeric excess at 45 °C. Candida antarctica lipase types A (CAL-A) and B (CAL-B) displayed the best activities and stereopreferences, with a dramatic influence being observed depending on the diamine structure. Non substituted and para-substituted aryldiamines led to the formation of allyl carbamates with good enantiomeric excess, using CAL-A for the less hindered substrates and CAL-B for the more hindered ones. On the other hand meta- and ortho-derivatives afforded low or negligible conversions and selectivities, respectively.     

Development of general methods for the synthesis of new substituted allyl bromides as promising alkenylating agents

A general procedure has been developed for the synthesis of hitherto unknown substituted allyl bromides. The procedure includes preparation of the corresponding α,β-unsaturated carboxylic acid esters from accessible ketones according to the Horner-Emmons reaction, reduction of these esters with diisobutylaluminum hydride to allylic alcohols, and substitution of the hydroxy group by bromine by the action of PBr₃. The E,Z isomer ratio of the synthesized unsaturated compounds ranges from 3: 1 to 4: 1.     

Synthesis of 1,2-Bis[propargyl(or allyl)oxy]cycloalkanes

Reactions of cyclic olefins with propargyl and allyl alcohols in the presence of crystalline iodine and a catalytic amount of Ag₃PW₁₂O₄₀ afforded in one step trans-1,2-bis[propargyl(allyl)oxy]cycloalkanes.     

An efficient stereoselective synthesis of enantiomerically pure aziridine derivatives of allyl β-d-glucopyranosides asymmetrically induced by a glucide moiety

The enantiomerically pure title aziridines were obtained by regioselective azidolysis of the 2′,3′-epoxy derivatives of allyl 3,4,6-tri-O-benzyl-β-d-glucopyranosides, followed by cyclization of the corresponding azido alcohols by means of the PPh₃ protocol. Enantiomerically pure starting epoxides were prepared by epoxidation of the corresponding allyl 3,4,6-tri-O-benzyl-β-d-glucopyranosides asymmetrically induced by a glucide moiety.     

Ring-closing metathesis of chiral allylamines. Enantioselective synthesis of (2S,3R,4S)-3,4-dihydroxyproline

The ring-closing metathesis (RCM) of two types of unsaturated chiral allylamines III, easily available from enantiomerically enriched epoxy alcohols, has been studied. Fully protected allylamines IIIa [(1)R = CH(2)-(CH(2))(n)()-CH=CH(2); (2)R = Boc; (3)R = PMB] have been prepared from unsaturated epoxy alcohols, whereas bis-allylamines IIIb ((1)R = Ph, (2)R = allyl,(3)R = Boc or PMB) have been prepared from 2,3-epoxy-3-phenylpropanol. Both types have been subjected to RCM to provide either cyclic allylamine I or II. The synthetic potential of these intermediates has been demonstrated by the enantioselective synthesis of (2S,3R,4S)-3,4-dihydroxyproline.     

Combining Matteson Homologations and Claisen Rearrangements – An Efficient Protocol for Amino Acid Synthesis

The Matteson homologation with vinyl nucleophiles was found to be an efficient and versatile protocol for the synthesis of substituted chiral allyl alcohols in a highly stereoselective fashion. These alcohols can be coupled with N-protected glycine and subsequently subjected to zinc-chelated ester-enolate Claisen rearrangements to yield highly substituted unsaturated amino acids. By varying the nucleophiles used in the Matteson homologations, the method allows control over not only the stereogenic centers but also the side-chain substitution pattern in the newly formed γ,δ-unsaturated amino acids.     

Effects of ring substituents on enantioselective recognition of amino alcohols and acids in uryl-based binol receptors

The uryl-based binol aldehyde, (S)-2-hydroxy-2′-(3-phenyluryl-benzyl)-1,1′-binaphthyl-3-carboxaldehyde (1), binds 1,2-amino alcohols and amino acids stereoselectively by reversible formation of imine bond. Hydrogen bond (between uryl group and alcohol -OH moiety) plays an important role in the stereoselectivity of amino alcohols. Hence, any substituents on phenyl group in 1 are expected to affect H-bond ability of uryl group. To study the effects of ring substituents on the stereoselective recognition of amino alcohols, (substituted phenyl)uryl-based chiral binol receptors have been prepared. The receptors with electron-donating X substituents have been synthesized from (S)-2-methoxymethoxy-2′-hydroxy-1,1′-binaphthyl-3-carboxaldehyde and X-phenyluryl-benzyl bromide. The receptors with electron-withdrawing Y substituents, however, required a different synthetic strategy including transformation of an aldehyde to alcohol. The incorporation of the electron withdrawing groups slightly accelerated the stereoselective recognition property of the receptor. Though the acceleration is not so remarkable, this work demonstrates the versatile derivatization of 1 in achieving higher stereoselective recognition of 1,2-amino alcohols and stereoconversion of l-amino acids to d-amino acids.     

Synthesis of β,β′-diamino acids from α-amino acid-derived β-lactams by ring opening with nucleophiles. Utilization in the synthesis of peptidomimetics

Ring opening of protected 3-aminoalkyl-substituted azetidin-2-ones with O-, N- or S-nucleophiles led to β,β′-diaminocarboxylic esters, amides and thioesters, respectively. The reaction outcome is improved by the addition of catalytic amounts of sodium azide. Utilization of a glycine derivative with unprotected amino function as nucleophile was possible. When bulkier amino acid esters were used, the intermediate acid azide underwent a Curtius rearrangement. The isocynates formed were trapped as the corresponding urea derivatives. Reduction of β-lactam's amide moiety led to diaminoalcohols.     

Ether formation from allylic alcohols catalyzed by samarium trichloride

The behaviour of various allylic alcohols in the presence of catalytic amounts of SmCl₃ (by heating in 1,2-dichloroethane) has been studied. Diallyl ethers are obtained in many cases in good yields. Mixed allyl alkyl ethers are also prepared if 2–5 equivalents of an aliphatic alcohol is present. The reactions are interpreted as proceeding through a pseudo allylic carbonium intermediate initiated by a preliminary complexation of the allyl hydroxyl to the samarium ion.     

Pd-catalyzed nucleophilic allylic alkylation of aliphatic aldehydes by the use of allyl alcohols

Under catalysis of Pd(OAc)₂-(P-n-Bu)₃, Et₂Zn promotes a variety of allyl alcohols to undergo nucleophilic allylation of aliphatic aldehydes and ketones at room temperature and provides homoallyl alcohols in 60-90 and ca. 60% isolated yield, respectively. The reaction is irreversible and kinetically controlled, and unique regio- and stereoselectivities observed for the allylation with unsymmetrically substituted allyl alcohols are discussed.     

Novel thiourea derivatives of α-amino acids and their oxorhenium(V) complexes

N-[(Dialkylamino)(thiocarbonyl)]benzimidoyl chlorides react with α-amino acid esters under formation of the corresponding N-[(dialkylamino)(thiocarbonyl)]benzamidines. Derivatives with glycine ethylester, HL(GlyOEt), cysteine methylester and S-benzyl protected cysteine ethylester, HL(S-Bzl-CysOEt), were prepared and isolated in crystalline form. The reaction with cysteine methylester yields the corresponding sulfur-bridged dimeric compound {HL(CysOMe)}₂.     

Practical Preparation of Z‐α‐(N‐Acetylamino)‐ and Z‐α‐(N‐Benzoylamino)‐α,β‐unsaturated Acids

An efficient two‐step synthetic procedure for the preparation of numerous variations of N‐protected α,β‐unsaturated α‐amino acids and their corresponding esters from N‐protected glycine and either aliphatic or aromatic aldehydes was developed. The reaction involved cyclization of the N‐protected glycine into oxazolone, condensation with the aldehyde, and ring opening with a base.     

Concise [4+3] cycloaddition reaction of pyrroles leading to tropinone derivatives

A concise [4+3] cycloaddition reaction of pyrroles with 2-(silyloxy)allyl cations has been developed. The oxyallyl cations stabilized with a methylthio group or geminal methyl groups were generated from the corresponding allylic alcohols under the influence of a Brönsted acid (Tf₂NH), respectively. The use of N-nosyl-protected pyrroles as the four-carbon unit was found to give tropinone derivatives in high yield.     

New C2-symmetric chiral phosphinite ligands based on amino alcohol scaffolds and their use in the ruthenium-catalysed asymmetric transfer hydrogenation of aromatic ketones

Asymmetric transfer hydrogenation processes of ketones with chiral molecular catalysts are attracting increasing interest from synthetic chemists due to their operational simplicity. C₂-symmetric catalysts have also received much attention and been used in many reactions. A series of new chiral C₂-symmetric bis(phosphinite) ligands has been prepared from corresponding amino acid derivated amino alcohols or (R)-2-amino-1-butanol through a three- or four-step procedure. Their structures have been elucidated by a combination of multinuclear NMR spectroscopy, IR spectroscopy and elemental analysis. ¹H-³¹P NMR, DEPT, ¹H-¹³C HETCOR or ¹H-¹H COSY correlation experiments were used to confirm the spectral assignments. In situ prepared ruthenium catalytic systems were successfully applied to ruthenium-catalyzed asymmetric transfer hydrogenation of acetophenone derivatives by iso-PrOH. Under optimized conditions, these chiral ruthenium catalyst systems serve as catalyst precursors for the asymmetric transfer hydrogenation of acetophenone derivatives in iso-PrOH and act as good catalysts, giving the corresponding optical secondary alcohols in 99% yield and up to 79% ee.     

An efficient synthesis of enantiopure (+)- and (−)-3-exo-amino-7,7-dimethoxynorbornan-2-exo-ols

We describe the synthesis of new amino alcohols (+)- and (−)-3-exo-amino-7,7-dimethoxynorbonan-2-exo-ols. The (+)- or (−)-7,7-dimethoxy-1,4,5,6-tetrachlorobicyclo[2.2.1]hept-5-en-2-endo-ol, obtained from the enzyme catalysed transesterification of the racemate, was reduced and dechlorinated (Na/NH₃; ethanol), followed by pyridinium chlorochromate oxidation of the resultant alcohols to the corresponding ketones. After treatment with t-BuOK/BuONO, in a nitrosation reaction, α-keto oximes were obtained. Reduction over two steps with NaBH₄ and NaBH₄/NiCl₂·6H₂O followed by in situ acetylation furnished the corresponding acetamido esters, which were hydrolysed with CH₃OH/Na to produce the enantiopure amino alcohols in good yields.     

Introduction of the Aib-Pro unit into peptides by means of the ‘azirine/oxazolone method’ on solid phase

A method for the direct introduction of Aib-Pro into peptides on solid phase was developed. The Aib-Pro unit was introduced by means of the ‘azirine/oxazolone method’ using allyl N-(2,2-dimethyl-2H-azirin-3-yl)-l-prolinate as the synthon. After the reaction of the resin-bound amino or peptide acid with allyl N-(2,2-dimethyl-2H-azirin-3-yl)-l-prolinate, the allyl protecting group of the resulting extended peptide could be removed by a mild Pd⁰-promoted procedure. Cleavage of the peptide from the resin was performed with UV light at 352 nm and yielded C-terminal protected peptides. The method found a successful application in the syntheses of different Aib-Pro containing peptaibol segments. Furthermore, a protected derivative of the peptide antibiotic Trichovirin I 1B was prepared by segment condensation.     

Base-Mediated Claisen Rearrangement of CF3-Containing Bisallyl Ethers

We have previously clarified that the strongly electron-withdrawing CF₃ group nicely affected the base-mediated proton shift of CF₃-containing propargylic or allylic alcohols to afford the corresponding α,β-unsaturated or saturated ketones, respectively, which was applied this time to the Claisen rearrangement after O-allylation of the allylic alcohols with a CF₃ group, followed by isomerization to the corresponding allyl vinyl ethers via the proton shift, enabling the desired rearrangement in a tandem fashion, or in a stepwise manner, the latter of which was proved to have attained an excellent diastereoselectivity with the aid of a palladium catalyst.     

Synthesis of bi- and tetracatenar highly fluorinated compounds for grafting on silicone materials

A series of highly fluorinated compounds bearing two or four perfluoroalkyl (R_F) chains, with a flexible or rigid core have been synthesized. Radical additions, nucleophilic addition or condensation reactions were implemented for these synthesis, using perfluoroalkylated iodides and alcohols and various type of substrates: bis(allylic) derivatives, epichlorhydrin, diacid derivatives. All compounds contain an unsaturated moiety (vinyl, allyl or internal double bond) to be grafted on silicone materials by a catalyzed hydrosilylation reaction.     

Organosilicon compounds of the furan series VIII. Reaction of triethylsilane with unsaturated alcohols

When triethylsilane is reacted with unsaturated primary alcohols such as allyl, cinnamic, and furylallyl alcohols, in the presence of H₂PtCl₆, the main reaction is one of dehydrocondensation. With secondary unsaturated alcohols such as methylallylcarbinol and furylallylcarbinol, dehydrocondensation and hydrosilylation take place simultaneously. A number of new furylalkoxy- and furyl-alkenoxysilanes are synthesized and described.