Synthesis and Reactivity of 2‐(6,7‐Diethoxy‐3,4‐dihydroisoquinolin‐ 1‐yl)acetonitrile towards Hydrazonoyl Halides

The synthesis of 2‐(6,7‐diethoxy‐3,4‐dihydroisoquinolin‐1‐yl)acetonitrile ( 1 ) has been performed by ring closure of the corresponding amide according to the Bischler‐Napieralski method (Scheme 1). Based on spectroscopic data, the tautomeric 2‐(tetrahydroisoquinolin‐1‐ylidene)acetonitrile is the actual compound. The reactions of 1 with α‐oxohydrazonoyl halides 4 in the presence of Et₃N led to 2‐(aryldiazenyl)pyrrolo[2,1‐a]isoquinoline derivatives 8 (Scheme 2), whereas with C‐(ethoxycarbonyl)hydrazonoyl chlorides 14 , 2‐(arylhydrazono)pyrrolo[2,1‐a]isoquinoline‐1‐carbonitriles 16 were formed (Scheme 4). The structures of the products were established from their analytical and spectroscopic data and, in the case of 8b , by X‐ray crystallography.     

On the Formation of 2‐Sulfonylbenzo[a]heptalene‐1,3‐diols as Precursors for the Synthesis of Colchicinoids

The benzo[a]heptalene formation from 4‐[(R‐sulfonyl)acetyl]heptalene‐5‐carboxylates 15 and 5‐[(R‐sulfonyl)acetyl]heptalene‐4‐carboxylates 16 (R=Ph or morpholino) in the presence of R′SO₂CH₂Li and BuLi has been investigated (Scheme 6). Only the sulfonyl moiety linked to the C?O group at C(4) of the heptalene skeleton is found at C(3) of the formed benzo[a]heptalene‐2,4‐diols 3 in accordance with the general mechanism of their formation (Scheme 3). Intermediates that might rearrange to corresponding 2‐sulfonylbenzo[a]heptalene‐1,3‐diols lose HO^? under the reaction conditions to yield the corresponding cyclopenta[d]heptalenones of type 11 (Schemes 6 and 7). However, the presence of an additional Me group at C(α) of the lithioalkyl sulfones suppresses the loss of HO^?, and 4‐methyl‐2‐sulfonylbenzo[a]heptalene‐1,3‐diols of type 4c have been isolated and characterized for the first time (Schemes 8 and 10). A number of X‐ray crystal‐structure analyses of starting materials and of the new benzo[a]heptalenes have been performed. Finally, benzo[a]heptalene 4c has been transformed into its 1,2,3‐trimethoxy derivative 23 , a benzo[a]heptalene with the colchicinoid substitution pattern at ring A (Scheme 11).     

Synthesis of Derivatives of the Optically Active β‐Amino Acids from (+)‐Car‐2‐ene

The reaction of (+)‐car‐2‐ene ( 4 ) with chlorosulfonyl isocyanate (=sulfuryl chloride isocyanate; ClSO₂NCO) led to the tricyclic lactams 6 and 8 corresponding to the initial formation both of the tertiary carbenium and α‐cyclopropylcarbenium ions (Scheme 2). A number of optically active derivatives of β‐amino acids which are promising compounds for further use in asymmetric synthesis were synthesized from the lactams (see 16, 17 , and 19 – 21 in Scheme 3).     

Halogenation of Fluorinated 1,3,5‐Triketones

The behavior of linear and cyclic fluorinated 1,3,5‐triketones and their metal derivatives towards common halogenating agents was examined, and optimal reaction conditions for the straightforward synthesis of mono‐, di‐, and tetrahalogenated products were found (Schemes 1–3). An aromatization through a double HBr elimination from an α,α′‐dibrominated cyclohexanone was shown to be a promising synthetic route to 1,1′‐(2‐hydroxy‐1,3‐phenylene)bis[2,2,2‐trifluoroethanones] (= 2,6‐bis(trifluoroacetyl)phenols; Scheme 4). Additionally, the 1,3,5‐triketones prepared add readily H₂O or alcohols to produce novel bridged 2,6‐dihydroxypyran‐4‐ones (Scheme 2). The structure of the obtained compounds 6a and 7a was confirmed by X‐ray structure analysis.     

Formation of 6,10‐Diphenyl‐Substituted Heptalene‐4,5‐dicarboxylates

It is shown that 4,8‐diphenylazulene ( 1 ) can be easily prepared from azulene by two consecutive phenylation reactions with PhLi, followed by dehydrogenation with chloranil. Similarly, a Me group can subsequently be introduced with MeLi at C(6) of 1 (Scheme 2). This methylation led not only to the expected main product, azulene 2 , but also to small amounts of product 3 , the structure of which has been determined by X‐ray crystal‐structure analysis (cf. Fig. 1). As expected, the latter product reacts with chloranil at 40° in Et₂O to give 2 in quantitative yields. Vilsmeier formylation of 1 and 2 led to the formation of the corresponding azulene‐1‐carbaldehydes 4 and 5 . Reduction of 4 and 5 with NaBH₄/BF₃ ? OEt₂ in diglyme/Et₂O 1 : 1 and BF₃ ? OEt₂, gave the 1‐methylazulenes 6 and 7 , respectively. In the same way was azulene 9 available from 6 via Vilsmeier formylation, followed by reduction of azulene‐1‐carbaldehyde 8 (Scheme 3). The thermal reactions of azulenes 1, 6 , and 7 with excess dimethyl acetylenedicarboxylate (ADM) in MeCN at 100° during 72 h afforded the corresponding heptalene‐4,5‐dicarboxylates 11, 12 , and 13 , respectively (Scheme 4). On the other hand, the highly substituted azulene 9 gave hardly any heptalene‐4,5‐dicarboxylate.     

7‐Halogenated 7‐Deazapurine 2′‐Deoxyribonucleosides Related to 2′‐Deoxyadenosine, 2′‐Deoxyxanthosine,and 2′‐Deoxyisoguanosine: Syntheses and Properties

A series of 7‐fluorinated 7‐deazapurine 2′‐deoxyribonucleosides related to 2′‐deoxyadenosine, 2′‐deoxyxanthosine, and 2′‐deoxyisoguanosine as well as intermediates 4b – 7b, 8, 9b, 10b , and 17b were synthesized. The 7‐fluoro substituent was introduced in 2,6‐dichloro‐7‐deaza‐9H‐purine ( 11a ) with Selectfluor (Scheme 1). Apart from 2,6‐dichloro‐7‐fluoro‐7‐deaza‐9H‐purine ( 11b ), the 7‐chloro compound 11c was formed as by‐product. The mixture 11b / 11c was used for the glycosylation reaction; the separation of the 7‐fluoro from the 7‐chloro compound was performed on the level of the unprotected nucleosides. Other halogen substituents were introduced with N‐halogenosuccinimides ( 11a → 11c – 11e ). Nucleobase‐anion glycosylation afforded the nucleoside intermediates 13a – 13e (Scheme 2). The 7‐fluoro‐ and the 7‐chloro‐7‐deaza‐2′‐deoxyxanthosines, 5b and 5c , respectively, were obtained from the corresponding MeO compounds 17b and 17c , or 18 (Scheme 6). The 2′‐deoxyisoguanosine derivative 4b was prepared from 2‐chloro‐7‐fluoro‐7‐deaza‐2′‐deoxyadenosine 6b via a photochemically induced nucleophilic displacement reaction (Scheme 5). The pK_a values of the halogenated nucleosides were determined (Table 3). ¹³C‐NMR Chemical‐shift dependencies of C(7), C(5), and C(8) were related to the electronegativity of the 7‐halogen substituents (Fig. 3). In aqueous solution, 7‐halogenated 2′‐deoxyribonucleosides show an approximately 70% S population (Fig. 2 and Table 1).     

Oxidative Fragmentations of the 5α‐ and 5β‐Hydroxy‐B‐norcholestan‐ 3β‐yl Acetates

Oxidations of 5α‐hydroxy‐B‐norcholestan‐3β‐yl acetate ( 8 ) with Pb(OAc)₄ under thermal or photolytic conditions or in the presence of iodine afforded only complex mixtures of compounds. However, the HgO/I₂ version of the hypoiodite reaction gave as the primary products the stereoisomeric (Z)‐ and (E)‐1(10)‐unsaturated 5,10‐seco B‐nor‐derivatives 10 and 11 , and the stereoisomeric (5R,10R)‐ and (5S,10S)‐acetals 14 and 15 (Scheme 4). Further reaction of these compounds under conditions of their formation afforded, in addition, the A‐nor 1,5‐cyclization products 13 and 16 (from 10 ) and 12 (from 11 ) (see also Scheme 6) and the 6‐iodo‐5,6‐secolactones 17 and 19 (from 14 and 15 , resp.) and 4‐iodo‐4,5‐secolactone 18 (from 15 ) (see also Scheme 7). Oxidations of 5β‐hydroxy‐B‐norcholestan‐3β‐yl acetate ( 9 ) with both hypoiodite‐forming reagents (Pb(OAc)₄/I₂ and HgO/I₂) proceeded similarly to the HgO/I₂ reaction of the corresponding 5α‐hydroxy analogue 8 . Photolytic Pb(OAc)₄ oxidation of 9 afforded, in addition to the (Z)‐ and (E)‐5,10‐seco 1(10)‐unsaturated ketones 10 and 11 , their isomeric 5,10‐seco 10(19)‐unsaturated ketone 22 , the acetal 5‐acetate 21 , and 5β,19‐epoxy derivative 23 (Scheme 9). Exceptionally, in the thermal Pb(OAc)₄ oxidation of 9 , the 5,10‐seco ketones 10, 11 , and 22 were not formed, the only reaction being the stereoselective formation of the 5,10‐ethers with the β‐oriented epoxy bridge, i.e. the (10R)‐enol ether 20 and (5S,10R)‐acetal 5‐acetate 21 (Scheme 8). Possible mechanistic interpretations of the above transformations are discussed.     

Enzyme‐Mediated Preparation of (+)‐ and (−)‐β‐Irone and (+)‐ and (−)‐cis‐γ‐Irone from Irone alpha®

The (−)‐ and (+)‐β‐irones ((−)‐ and (+)‐ 2 , resp.), contaminated with ca. 7 – 9% of the (+)‐ and (−)‐trans‐α‐isomer, respectively, were obtained from racemic α‐irone via the 2,6‐trans‐epoxide (±)‐ 4 (Scheme 2). Relevant steps in the sequence were the LiAlH₄ reduction of the latter, to provide the diastereoisomeric‐4,5‐dihydro‐5‐hydroxy‐trans‐α‐irols (±)‐ 6 and (±)‐ 7 , resolved into the enantiomers by lipase‐PS‐mediated acetylation with vinyl acetate. The enantiomerically pure allylic acetate esters (+)‐ and (−)‐ 8 and (+)‐ and (−)‐ 9 , upon treatment with POCl₃/pyridine, were converted to the β‐irol acetate derivatives (+)‐ and (−)‐ 10 , and (+)‐ and (−)‐ 11 , respectively, eventually providing the desired ketones (+)‐ and (−)‐ 2 by base hydrolysis and MnO₂ oxidation. The 2,6‐cis‐epoxide (±)‐ 5 provided the 4,5‐dihydro‐4‐hydroxy‐cis‐α‐irols (±)‐ 13 and (±)‐ 14 in a 3 : 1 mixture with the isomeric 5‐hydroxy derivatives (±)‐ 15 and (±)‐ 16 on hydride treatment (Scheme 1). The POCl₃/pyridine treatment of the enantiomerically pure allylic acetate esters, obtained by enzymic resolution of (±)‐ 13 and (±)‐ 14 , provided enantiomerically pure cis‐α‐irol acetate esters, from which ketones (+)‐ and (−)‐ 22 were prepared (Scheme 4). The same materials were obtained from the (9S) alcohols (+)‐ 13 and (−)‐ 14 , treated first with MnO₂, then with POCl₃/pyridine (Scheme 4). Conversely, the dehydration with POCl₃/pyridine of the enantiomerically pure 2,6‐cis‐5‐hydroxy derivatives obtained from (±)‐ 15 and (±)‐ 16 gave rise to a mixture in which the γ‐irol acetates 25a and 25b and 26a and 26b prevailed over the α‐ and β‐isomers (Scheme 5). The (+)‐ and (−)‐cis‐γ‐irones ((+)‐ and (−)‐ 3 , resp.) were obtained from the latter mixture by a sequence involving as the key step the photochemical isomerization of the α‐double bond to the γ‐double bond. External panel olfactory evaluation assigned to (+)‐β‐irone ((+)‐ 2 ) and to (−)‐cis‐γ‐irone ((−)‐ 3 ) the strongest character and the possibility to be used as dry‐down note.     

Synthesis of (±)‐Kempa‐6,8‐dien‐3‐ol (=(2aRS,3SR,4aSR,7RS,7aSR,10bSR,10cSR)‐2,2a,3,4,4a,5,6,7,7a,8,10b,10c‐Dodecahydro‐2a,7,10,10c‐tetramethylnaphth[2,18‐cde]azulen‐3‐ol)

The synthesis of kempa‐6,8‐dien‐3β‐ol ( 4a ), as a synthetic leading model of the natural product 4b , was carried out starting from intermediate 12 , the synthetic route of which has been developed previously (Scheme 1). The conversion of 12 to the model compound 4a involved the elaboration of three structure modifications by three processes, Tasks A, B, and C (see Scheme 2). Task A was achieved by epoxy‐ring opening of 41 with Me₃SiCl (Scheme 9), and Task B being performed by oxidation at the 13‐position, followed by hydrogenation, and then epimerization (Schemes 4 and 5). The removal of the 2‐OH group from 12 (Task C) was achieved via 30b according to Scheme 6, whereby 30b was formed exclusively from 30a / 31a 1 : 1 (Scheme 7). In addition, some useful reactions from the synthetic viewpoint were developed during the course of the present experiments.     

A Direct Synthesis of Nucleoside Analogs Homologated at the 3′‐ and 5′‐Positions

A new route is presented to prepare analogs of nucleosides homologated at the 3′‐ and 5′‐positions. This route, applicable to both the D ‐ and L ‐enantiomeric forms, is suitable for the preparation of monomeric bis‐homonucleosides needed for the synthesis of oligonucleotide analogs. It begins with the known monobenzyl ether 3 of pent‐2‐yne‐1,5‐diol, which is reduced to alkenol 4 . Sharpless asymmetric epoxidation of 4 , followed by opening of the epoxide 5 with allylmagnesium bromide, gives a mixture of diols 6 and 7 . Protection of the primary alcohol as a silyl ether followed by treatment with OsO₄, NaIO₄, and mild acid in MeOH, followed by reduction, yields (2R,3R) {{[(tert‐butyl)diphenylsilyl]oxy}methyl}tetrahydro‐2‐(2‐hydroxyethyl)‐5‐methoxyfuran (=methyl 3‐{{[(tert‐butyl)diphenylsilyl]oxy}methyl}‐2,3,5‐trideoxy‐α/β‐D ‐erythro‐hexafuranoside; 10 ) (Scheme 1). Protected nucleobases are added to this skeleton with the aid of trimethylsilyl triflate (Scheme 2). The o‐toluoyl (2‐MeC₆H₄CO) and p‐anisoyl (4‐MeOC₆H₄CO) groups were used to protect the exocyclic amino group of cytosine. The bis‐homonucleoside analogs 11 and 14a are then converted to monothiol derivatives suitable for coupling (Schemes 3 and 4) to oligonucleotide analogs with bridging S‐atoms. This synthesis replaces a much longer synthesis for analogous nucleoside analogs that begins with diacetoneglucose (=1,2 : 5,6‐di‐O‐isopropylideneglucose), with the stereogenic centers in the final products derived from the Sharpless asymmetric epoxidation. The new route is useful for large‐scale synthesis of these building blocks for the synthesis of oligonucleotide analogs.     

Synthesis of Bis(2,4‐diarylimidazol‐5‐yl) Diselenides from N‐Benzylbenzimidoyl Isoselenocyanates

The reaction of N‐benzylbenzamides 6 with SOCl₂ under reflux gave the corresponding N‐benzylbenzimidoyl chlorides 7 . Further treatment with KSeCN in dry acetone yielded imidoyl isoselenocyanates 3 (Scheme 2). These compounds, obtained in satisfying yields, proved to be stable enough to be purified and analyzed. Reaction of 3 with morpholine in dry acetone led to the corresponding selenourea derivatives 8 . On treatment with Et₃N, the 4‐nitrobenzyl derivatives of type 3 were transformed into bis(2,4‐diarylimidazol‐5‐yl) diselenides 9 (Scheme 3). This transformation takes place only when the benzyl residue bears an NO₂ group and the phenyl group is not substituted with a strong electron‐donating group. A reaction mechanism for the formation of 9 is proposed in Scheme 4. The key structures have been established by X‐ray crystallography.     

One‐Pot Synthesis of 4‐(Alkylamino)‐1‐(arylsulfonyl)‐3‐benzoyl‐1,5‐ dihydro‐5‐hydroxy‐5‐phenyl‐2H‐pyrrol‐2‐ones via a Multicomponent Reaction

An effective route to novel 4‐(alkylamino)‐1‐(arylsulfonyl)‐3‐benzoyl‐1,5‐dihydro‐5‐hydroxy‐5‐phenyl‐2H‐pyrrol‐2‐ones 10 is described (Scheme 2). This involves the reaction of an enamine, derived from the addition of a primary amine 5 to 1,4‐diphenylbut‐2‐yne‐1,4‐dione, with an arenesulfonyl isocyanate 7 . Some of these pyrrolones 10 exhibit a dynamic NMR behavior in solution because of restricted rotation around the C? N bond resulting from conjugation of the side‐chain N‐atom with the adjacent α,β‐unsaturated ketone group, and two rotamers are in equilibrium with each other in solution ( 10 ? 11 ; Scheme 3). The structures of the highly functionalized compounds 10 were corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS), by elemental analyses, and, in the case of 10a , by X‐ray crystallography. A plausible mechanism for the reaction is proposed (Scheme 4).     

Preparation of the β3‐Homoselenocysteine Derivatives Fmoc‐β3hSec(PMB)‐OH and Boc‐β3hSec(PMB)‐OH for Solution and Solid‐Phase‐Peptide Synthesis and Selenoligation

The title compounds, 4 and 7 , have been prepared from the corresponding α‐amino acid derivative selenocystine ( 1 ) by the following sequence of steps: cleavage of the Se? Se bond with NaBH₄, p‐methoxybenzyl (PMB) protection of the SeH group, Fmoc or Boc protection at the N‐atom and Arndt–Eistert homologation (Schemes 1 and 2). A β³‐heptapeptide 8 with an N‐terminal β³‐hSec(PMB) residue was synthesized on Rink amide AM resin and deprotected (‘in air’) to give the corresponding diselenide 9 , which, in turn, was coupled with a β³‐tetrapeptide thiol ester 10 by a seleno‐ligation. The product β³‐undecapeptide was identified as its diselenide and its mixed selenosulfide with thiophenol (Scheme 3). The differences between α‐ and β‐Sec derivatives are discussed.     

Selenium‐Containing Heterocycles from Isoselenocyanates: Synthesis of 5‐Amino‐2,4‐dihydro‐3H‐1,2,4‐triazole‐3‐selones

The reaction of S‐methylisothiosemicarbazide hydroiodide (=S‐methyl hydrazinecarboximidothioate hydroiodide; 1 ), prepared from thiosemicarbazide by treatment with MeI in EtOH, and aryl isoselenocyanates 5 in CH₂Cl₂ affords 3H‐1,2,4‐triazole‐3‐selone derivatives 7 in good yield (Scheme 2, Table 1). During attempted crystallization, these products undergo an oxidative dimerization to give the corresponding bis(4H‐1,2,4‐triazol‐3‐yl) diselenides 11 (Scheme 3). The structure of 11a was established by X‐ray crystallography.     

Synthesis of Bis‐Heterocyclic 1H‐Imidazole 3‐Oxides from 3‐Oxido‐1H‐imidazole‐4‐carbohydrazides

The reaction of 1H‐imidazole‐4‐carbohydrazides 1 , which are conveniently accessible by treatment of the corresponding esters with NH₂NH₂?H₂O, with isothiocyanates in refluxing EtOH led to thiosemicarbazides (=hydrazinecarbothioamides) 4 in high yields (Scheme 2). Whereas 4 in boiling aqueous NaOH yielded 2,4‐dihydro‐3H‐1,2,4‐triazole‐3‐thiones 5 , the reaction in concentrated H₂SO₄ at room temperature gave 1,3,4‐thiadiazol‐2‐amines 6 . Similarly, the reaction of 1 with butyl isocyanate led to semicarbazides 7 , which, under basic conditions, undergo cyclization to give 2,4‐dihydro‐3H‐1,2,4‐triazol‐3‐ones 8 (Scheme 3). Treatment of 1 with Ac₂O yielded the diacylhydrazine derivatives 9 exclusively, and the alternative isomerization of 1 to imidazol‐2‐ones was not observed (Scheme 4). It is important to note that, in all these transformations, the imidazole N‐oxide residue is retained. Furthermore, it was shown that imidazole N‐oxides bearing a 1,2,4‐triazole‐3‐thione or 1,3,4‐thiadiazol‐2‐amine moiety undergo the S‐transfer reaction to give bis‐heterocyclic 1H‐imidazole‐2‐thiones 11 by treatment with 2,2,4,4‐tetramethylcyclobutane‐1,3‐dithione (Scheme 5).     

A Novel,One‐Pot Four‐Component Route to 2′‐Thioxo‐2′,3′‐dihydrospiro[indole‐3,6′‐[1,3]thiazin]‐2‐one Derivatives

An efficient route to 2′,3′‐dihydro‐2′‐thioxospiro[indole‐3,6′‐[1,3]thiazin]‐2(1H)‐one derivatives is described. It involves the reaction of isatine, 1‐phenyl‐2‐(1,1,1‐triphenyl‐λ⁵‐phosphanylidene)ethan‐1‐one, and different amines in the presence of CS₂ in dry MeOH at reflux (Scheme 1). The alkyl carbamodithioate, which results from the addition of the amine to CS₂, is added to the α,β‐unsaturated ketone, resulting from the reaction between 1‐phenyl‐2‐(1,1,1‐triphenyl‐λ⁵‐phosphanylidene)ethan‐1‐one and isatine, to produce the 3′‐alkyl‐2′,3′‐dihydro‐4′‐phenyl‐2′‐thioxospiro[indole‐3,6′‐[1,3]thiazin]‐2(1H)‐one derivatives in excellent yields (Scheme 2). Their structures were corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS) and by elemental analyses.     

7‐Iodo‐5‐aza‐7‐deazaguanine: Syntheses of Anomeric D‐ and L‐Configured 2‐Deoxyribonucleosides

Iodination of N²‐isobutyryl‐5‐aza‐7‐deazaguanine ( 7 ) with N‐iodosuccinimide (NIS) gave 7‐iodo‐N²‐isobutyryl‐5‐aza‐7‐deazaguanine ( 8 ) in a regioselective reaction (Scheme 1). Nucleobase‐anion glycosylation of 8 with 2‐deoxy‐3,5‐di‐O‐toluoyl‐α‐D ‐ or α‐L ‐erythro‐pentofuranosyl chloride furnished anomeric mixtures of D ‐ and L ‐nucleosides. The anomeric D ‐nucleosides were separated by crystallization to give the α‐D ‐anomer and β‐D ‐anomer with excellent optical purity. Deprotection gave the 7‐iodo‐5‐aza‐7‐deazaguanine 2′‐deoxyribonucleosides 3 (β‐D ; ≥99% de) and 4 (α‐D ; ≥99% de). The reaction sequence performed with the D ‐series was also applied to L ‐nucleosides to furnish compounds 5 (β‐L ; ≥99% de) and 6 (α‐L ; ≥95% de).     

Synthesis of (2′S)‐2′‐Deoxy‐2′‐C‐methylpurine Nucleosides and Their Phosphoramidites

We describe the stereoselective synthesis of (2′S)‐2′‐deoxy‐2′‐C‐methyladenosine ( 12 ) and (2′S)‐2′‐deoxy‐2′‐C‐methylinosine ( 14 ) as well as their corresponding cyanoethyl phosphoramidites 16 and 19 from 6‐O‐(2,6‐dichlorophenyl)inosine as starting material. The methyl group at the 2′‐position was introduced via a Wittig reaction (→ 3 , Scheme 1) followed by a stereoselective oxidation with OsO₄ (→ 4 , Scheme 2). The primary‐alcohol moiety of 4 was tosylated (→ 5 ) and regioselectively reduced with NaBH₄ (→ 6 ). Subsequent reduction of the 2′‐alcohol moiety with Bu₃SnH yielded stereoselectively the corresponding (2′S)‐2′‐deoxy‐2′‐C‐methylnucleoside (→ 8a ).     

Preparation and Structures of 2‐Substituted 5‐Benzyl‐3‐methylimidazolidin‐4‐one‐Derived Iminium Salts,Reactive Intermediates in Organocatalytic Transformations Involving α,β‐Unsaturated Aldehydes

Preparations of the title compounds, 5 – 7 (Scheme 1 and Table 1), of their ammonium salts, 9 – 11 (Scheme 2 and Table 2), and of the corresponding cinnamaldehyde‐derived iminium salts 12 – 14 (Scheme 3 and Table 3) are reported. The X‐ray crystal structures of 15 cinnamyliminium PF₆ salts have been determined (Table 4). Selected ¹H‐NMR data (Table 5) of the ammonium and iminium salts are discussed, and structures in solution are compared with those in the solid state.     

Base‐Induced Decarboxylation of Polyunsaturated α‐Cyano Acids Derived from Malonic Acid: Synthesis of Sesquiterpene Nitriles and Aldehydes with β‐, φ‐, and ψ‐End Groups

Catalytic base‐induced decarboxylation of polyunsaturated α‐cyano‐β‐methyl acids derived from malonic acid led to the corresponding nitriles 3 (Schemes 2 and 3), 6 (Scheme 5), and 9 (Scheme 6). This decarboxylation occurred with previous deconjugation of the α,β‐alkene moiety of the α‐cyano‐β‐methyl acid, leading to an α‐cyano‐β‐methylene propanoic acid which was easily decarboxylated (see Scheme 2). β‐Methylene intermediates, in some cases, could be isolated; mechanistic pathways are proposed. The nitriles 3, 6 , and 9 were reduced to the sesquiterpene aldehydes 4 (β‐end group), 7 (φ‐end group), and 10 (ψ‐end group), respectively.