Photocycloaddition of Cyclohex‐2‐enones to 2‐Methylbut‐1‐en‐3‐yne

Irradiation (350 nm) of 2‐alkynylcyclohex‐2‐enones 1 in benzene in the presence of an excess of 2‐methylbut‐1‐en‐3‐yne ( 2 ) affords in each case a mixture of a cis‐fused 3,4,4a,5,6,8a‐hexahydronaphthalen‐1(2H)‐one 3 and a bicyclo[4.2.0]octan‐2‐one 4 (Scheme 2), the former being formed as main product via 1,6‐cyclization of the common biradical intermediate. The (parent) cyclohex‐2‐enone and other alkylcyclohex‐2‐enones 7 also give naphthalenones 8 , albeit in lower yields, the major products being bicyclo[4.2.0]octan‐2‐ones (Scheme 4). No product derived from such a 1,6‐cyclization is observed in the irradiation of 3‐alkynylcyclohex‐2‐enone 9 in the presence of 2 (Scheme 4). Irradiation of the 2‐cyano‐substituted cyclohexenone 12 under these conditions again affords only traces of naphthalenone 13 , the main product now being the substituted bicyclo[4.2.0]oct‐7‐ene 16 (Scheme 5), resulting from [2+2] cycloaddition of the acetylenic C−C bond of 2 to excited 12 .     

Electrophilic Bromination of N‐Acylated Cyclohex‐3‐en‐1‐amines: Synthesis of 7‐Azanorbornanes

The intramolecular bromo‐amidation and the dibromination‐cyclisation of the N‐acylcyclohex‐3‐en‐1‐amines 4, 8, 9, 11, 13, 14 , and 16 was studied in view of the synthesis of bicyclic amines that are of interest as building blocks and potential glycosidase inhibitors. The trifluoroacetamides 4, 9 , and 14 reacted with N‐bromosuccinimide (NBS) in AcOH to give dihydro‐1,3‐oxazines in good yields. The stereoselectivity of the dibromination of the alkenes 8 and 9 depends on the nature of the protecting group, the reagent, and the reaction conditions. Br₂ in CH₂Cl₂ transformed the alkenes 8 and 9 predominantly into diaxial trans,trans‐dibromides. Bromination of 9 with PhMe₃NBr₃ or with Br₂ in the presence of Et₄NBr gave predominantly the diequatorial trans,cis‐ 27 besides some trans,trans‐ 28 . A similar bromination of the C(5)‐substituted N‐acyl‐4‐aminocyclohexenes 11, 13, 14 , and 16 with PhMe₃NBr₃ was accompanied by intramolecular side reactions that were suppressed by the addition of excess Et₄NBr. Under these conditions, 11 gave diastereoselectively trans‐dibromides, while its reaction with Br₂ gave trans‐dibromides along with the dihydrooxazinone 31 . Also the carbamate 13 reacted with PhMe₃NBr₃/Et₄NBr selectively to the trans‐dibromide 32 and with Br₂ to the trans‐dibromides 32 and 33 , the dihydrooxazinone 34 , and the bicyclic ether 35 . Similarly, the trifluoroacetamide 14 provided the dibromide 36 (89%), while its reaction with Br₂ led to the dihydrooxazine 22 , and the dibromides 36 and 37 . The N‐benzyl‐N‐Boc derivative 16 did not yield any dibromide; it reacted with PhMe₃NBr₃/Et₄NBr to the dihydrooxazinone 38 , and with Br₂ to the oxazinone 38 and the bicyclic ether 39 . The high stereoselectivity of the bromination with PhMe₃NBr₃/Et₄NBr suggests an anchimeric assistance of the NHR substituent. Deprotection, cyclisation, and carbamoylation transformed the dibromides 27, 29 , and 32 into the 7‐azanorbornanes 42, 49 , and 53 . The diols 45 and 57 were obtained from 42 and 53 via HBr elimination and stereoselective dihydroxylation; they proved weak inhibitors of several glycosidases. In no case could the formation of a bicyclic azetidine (6‐azabicyclo[3.1.1]heptane) from the dibromides 26 and 30 be observed.     

Hexagonal packing of cis,cis‐cyclohexane‐1,3,5‐tricarboxamide

The title compound, C₉H₁₅N₃O₃, which has crystallographically imposed threefold symmetry, crystallizes as a hexagonal columnar structure. The crystal structure is stabilized by a less common amide–amide synthon, where one amide group is hydrogen bonded to four others. The amide groups form cyclic amide–amide hexamers via N—H...O hydrogen bonds.     

3β‐(1‐Allyl‐1‐pyrrolidinio)‐16‐(2‐pyridylmethylene)androst‐5‐en‐17β‐ol bromide hemihydrate

The title compound, C₃₂H₄₅N₂O⁺·Br^?·0.5H₂O, has the outer two six‐membered rings in chair conformations, while the central ring is in an 8β,9α‐half‐chair conformation. The five‐mem­bered ring of the steroid nucleus adopts a slightly deformed 14α‐envelope conformation. The pyridyl­methyl­ene moiety has an E configuration with respect to the hydroxyl group at position 17. The structure is stabilized by a network of O—H?Br‐type intermolecular hydrogen bonds.     

16‐(4‐Cyanobenzylidene)‐3β‐pyrrolidinoandrost‐5‐en‐17β‐ol monohydrate

In the title compound, C₃₁H₄₀N₂O·H₂O, the outer two six‐membered rings are in chair conformations, while the central ring is in an 8β,9α‐half‐chair conformation. The five‐membered ring adopts a 13β‐envelope conformation and the cyano­benzyl­idene moiety has an E configuration with respect to the hydroxyl group at position 17. The steroid nuclei are linked by intermolecular O—H?O and O—H?N hydrogen bonds to form a molecular network. The molecular packing has an interesting feature, with the steroids aligned parallel to the b axis, forming a closed loop through hydrogen bonds linked via water mol­ecules.     

Enantioselective Synthesis of Arene cis‐Dihydrodiols from 2‐Pyrones

An enantioselective chemical synthesis of arene cis‐dihydrodiols has been realized from 2‐pyrones through sequential ytterbium‐catalyzed asymmetric inverse‐electron‐demand Diels–Alder (IEDDA) reaction of 2‐pyrones and retro‐Diels–Alder extrusion of CO₂. By using this strategy, a series of substituted arene cis‐dihydrodiols can be obtained efficiently with high enantioselectivity (>99 % ee in many cases). Based on this strategy, efficient and concise asymmetric total syntheses of (+)‐MK7607 and 1‐epi‐(+)‐MK7607 were accomplished.     

Alternative Synthesis of 2‐Hydroxy‐3,5,5‐trimethylcyclopent‐2‐en‐1‐one

The 2‐hydroxy‐3,5,5‐trimethylcyclopent‐2‐en‐1‐one ( 1 ) was synthesized in 42% yield by rearrangement of epoxy ketone 10 on treatment with BF₃⋅Et₂O under anhydrous conditions. Intermediate 10 was available from the known enone 8 , either via direct epoxidation (60% H₂O₂, NaOH, MeOH; yield 50%), or via reduction to the corresponding allylic alcohol 14 (LiAlH₄, THF), followed by epoxidation ([VO(acac)₂], ^tBuOOH) and reoxidation under Swern conditions, in 37% total yield.     

Synthesis of 2‐Thioxohydropyridine‐3‐Carbonitrile, 2‐Alkylthiopyridine,Thienopyridine, Pyrazolopyridine Derivatives and Their Theoretical Calculations

Cyanothioacetamide ( 1 ) reacted with but‐2‐enal ( 2 ) to give the corresponding 4‐methyl‐2‐sulfanylpyridine‐3‐carbonitrile ( 7 ) which was used as a good starting material for the synthesis of 1‐(3‐amino‐4‐methylthieno[2,3‐b]pyridin‐2‐yl)ethan‐1‐one ( 10 ), 3‐amino‐4‐methylthieno[2,3‐b]pyridine‐2‐carboxamide ( 15 ), 3‐amino‐4‐methylthieno[2,3‐b]pyridine‐2‐carboxylate ( 18 ) and 3‐amino‐4‐methylthieno[2,3‐b]pyridin‐2‐ylarylketone 25a‐c through its reactions with each of (1‐chloroacetone ( 8 ), 3‐chloropentane‐2,4‐dione ( 11 ) or ethyl 2‐chloro‐3‐oxo‐butanoate ( 19 )), 2‐chloroacetamide ( 13 ), ethyl 2‐chloroacetate ( 16 ) and 2‐bromo‐1‐arylethan‐ 1 ‐one 23a‐c , respectively. Considering the data of elemental analyses, IR, ¹HNMR, mass spectra and theoretical calculations, structures of the newly synthesized heterocyclic compounds were elucidated.     

cis,cis,cis‐Tetra­methyl 1,2,4,5‐cyclo­hexane­tetra­carboxyl­ate

The title compound, C₁₄H₂₀O₈, was synthesized from the hydrogenation of tetra­methyl 1,4‐cyclo­hexa­diene‐1,2,4,5‐tetra­carboxyl­ate with a catalytic amount of palladium/carbon. All four carbonyl moieties of the methyl ester groups are on the same face of the chair‐conformed ring. The substantial ring distortion associated with the 1,3‐diaxial methoxycarbonyl substituents is reflected in the large difference between bond angles as well as torsion angles, respectively, that in undistorted cyclo­hexanes would be approximately the same.     

rac‐Eudesm‐7(11)‐en‐4‐ol

The isolation and structural determination of rac‐eudesm‐7(11)‐en‐4‐ol, C₁₅H₂₆O, from the steam distillate of the flowers of Dipterocarpus cornutus Dyer (Dipterocarpaceae) is described. The structure was determined from spectroscopic data and a single‐crystal X‐ray study. Two similar independent mol­ecules comprise the asymmetric unit of the structure.     

16‐(4‐Cyano­benzyl­idene)‐17‐oxo­androst‐5‐en‐3β‐ol

In the title compound, 4‐(3β‐hydroxy‐17‐oxoandrost‐5‐en‐16‐ylidenemethyl)benzonitrile, C₂₇H₃₁NO₂, rings A and C of the steroid nucleus are in chair conformations. The central six‐membered ring B is in an 8β,9α‐half‐chair conformation, while the five‐membered ring D adopts a 13β,14α‐half‐chair conformation. The cyano­benzyl­idene moiety has an E configuration with respect to the carbonyl group at position C17. The dihedral angle between the planes of the steroid nucleus and the cyano­benzyl­idene moiety is 22.61 (15)°. Intermolecular O—H⃛N hydrogen bonds formed between the hydroxyl group of the steroid and the N atom of the cyano­benzyl­idene moiety of symmetry‐related mol­ecules link the steroid mol­ecules into chains which run parallel to the b axis.     

17‐Oxo‐16‐(2‐pyridyl­methyl­ene)­androst‐5‐en‐3β‐ol monohydrate

The title compound, C₂₅H₃₁NO₂·H₂O, has the outer two six‐membered rings in chair conformations, while the central ring is in an 8β,9α‐half‐chair conformation. The five‐membered ring adopts a 13,14‐half‐chair conformation. The pyridyl­methyl­ene moiety has an E configuration with respect to the carbonyl group at position 17. The structure is stabilized by intermolecular O—H?N and O—H?O hydrogen bonds.     

cis,cis,cis‐1,2,4,5‐Cyclo­hexane­tetra­carboxyl­ic acid and its dianhydride

cis,cis,cis‐1,2,4,5‐Cyclo­hexane­tetra­carboxyl­ic acid, C₁₀H₁₂O₈, (I), contains a mirror plane and the cyclo­hexane ring exhibits a chair conformation. Two crystallographically independent hydrogen bonds form (14), (16) and (16) ring motifs, and propagation of these two hydrogen bonds along the c and b axes generates (16) and (7) chains. cis,cis,cis‐1,2:4,5‐Cyclo­hexane­tetra­carboxyl­ic dianhydride, C₁₀H₈O₆, (II), was prepared by the reaction of (I) with acetic anhydride. The cyclo­hexane ring of (II) exhibits a boat conformation and the dihedral angle between the two an­hydro rings is 117.5 (1)°.