The Homoconjugated Electron-Releasing Carbonyl Group of 1-Methylbicyclo[2.2.1]hept-5-en-2-one. Regioselective syntheses of 5-chloro- and 6-chloro-1-methylbicyclo[2.2.1]hept-5-en-2-one

Syntheses of (±)-2-exo-cyano-1-methyl-7-oxabicyclo[2.2.1]hept-5-en-2-endo-yl acetate ( 1 ) and of (±)-1-methyl-7-oxabicyclo[2.2.1]hept-5-en-2-one ( 2 ) are reported. The additon of PhSeCl to 1 afforded (±)-5-endo-chloro-2-exo-cyano-1-methyl-6-exo-(phenylselenenyl)-7-oxabicyclo[2.2.1]hept-2-endo-yl acetate ( 6 ), whereas 2 added to PhSeCl with the opposite regioselectivity giving (±)-6-endo-chloro-1-methyl-5-exo-(phenylselenenyl)-7-oxabicyclo[2.2.1]heptan-2-one ( 7 ). These adducts were converted into 5-chloro-1-methyl-7-oxabicyclo[2.2.1]hept-5-en-2-one ( 9 ) and 6-chloro-1-methyl-7-oxabicyclo[2.2.1]hept-5-en-2-one ( 10 ), respectively.     

Photoinduced Double Addition of Acetylene to 3-Oxocyclopent-1-ene-1-carbonitrile or 3-oxocyclopent-1-enyl acetate leading to 2,3-dihydro-1H-inden-1-one and other rearranged products

UV Irradiation of 3-oxocyclopent-1-enyl acetate ( 17 ) and acetylene in MeCN at 0° gives, besides the product of normal enone-alkyne [2 + 2] cycloaddition (cis-4-oxobicyclo[3.2.0] hept-6-en-1-yl acetate, 18 ) and its product of oxa-di-π-methane rearrangement (5-oxotricyclo[4.1.0.0^2,7]hept-2-yl acetate, 19 ), unexpected products of further addition of a molar equivalent of acetylene. These are indanone ( = 2,3-dihydro-1H-inden-1-one, 16 ), in 21% yield, cis-1-cisoid-1,2-cis-2- ( 20 ) and cis-1-transoid-1,2-cis-2-7-oxotricyclo[4.3.0.0^2,5]non-3-en-1-yl acetate ( 21 ), 4-oxo-7-‘exo’-vinyltricyclo[3.2.0.0^2,6]hept-2-yl acetate ( 22 ), cis-4-oxo-6-‘endo’- ( 23 ) and cis-4-oxo-6-‘exo’-vinylbicyclo[3.2.0]hept-1-yl acetate ( 24 ), and cis-4-oxo-7-‘exo’-vinylbicyclo[3.2.0]hept-1-yl acetate ( 25 ). At least in part, indanone must be formed via intermediates 20 and 21 . In fact, on heating a 9:1 mixture 20/21 , indanone is obtained quantitatively. With 3-oxocyclopent-1-ene-1-carbonitrile ( 15 ) in place of 17 , indanone is formed in lower (8%) yield besides much tars.     

Preparation of 7-Methyl-7-vinylbicyclo[3.2.0]hept-2-ene Via Cyclobutanone Reduction

A cyclobutanone to cyclobutane conversion has been performed on 7-methyl-7-vinylbicyclo[3.2.0]hept-2-en-6-one by low-temperature (25°C) Wolff-Kishner reduction of the hydrazone derivative. Upon heating, the exo-vinyl epimer affords predominantly cis-6-methyl-4,7,8,9-tetrahydroindene.     

Photochemical Synthesis and Some Reactions of 7-Oxa-and 7-Thiatricyclo[3.2.1.03,6]octan-2-ones

Irradiation (λ = 350 nm) of newly synthesized 2-acetyl- or 2-methyl-2-(alk-2-enyl)furan-3(2H)-ones 1 and 2-acetyl- or 2-methyl-2-(prop-2-enyl)thiophen-3(2H)-ones 2 affords the corresponding 1-acetyl- or 1-methyl-substituted 7-oxa- and 7-thiatricyclo[3.2.1.0^3,6]octan-2-ones 10 and 11 , respectively, via regioselective intramolecular [2 + 2] photocycloaddition in 65–95% yield (Scheme 2). The 1-acetyl-substituted O-derivatives 10b and 10c undergo ring opening on treatment with MeONa in MeOH at–78° to afford stereoselectively methyl 3-exo-acetyl-2-oxabicyclo[3.2.0]heptane-7-endo-carboxylates 12b and 12c , respectively, while a 2:1 diastereoisomeric mixture of methyl 3-acetyl-2-thiabicyclo[3.2.0]heptane-7-endo-carboxylates 13 and 14 is obtained from the corresponding S-derivative 11b . The outcome of the Huang-Minlon reduction of the 1-methyl-substituted ketones 10a and 11a is again influenced by the heteroatom in the tricycle. While 1-methyl-7-oxatricyclo[3.2.1.0^3,6]-octane ( 15 ) is the only product from the corresponding oxatricyclooctanone 10a , a 1:2 mixture of 1-methyl-7-thiatricyclo[3.2.1.0^3,6]-octane ( 16 ) and 3-methylbicyclo[3.1.1]hept-2-ene-6-endo-thiol ( 17 ) is obtained from the analogous S-compound 11a , both products stemming from a common carbanion precursor.     

Synthesis of (−)-Conduritol C (1L-Cyclohex-5-ene-1,2,3/4-tetrol)

(1R, 2R, 4R)-2-endo-Cyano-7-oxabicyclo[2.2.1]hept-5-en-2-yl acetate ((?)-7) has been transformed into the all-cis-configurated 4L -4,5,6/0-trihydroxycyclohex-2-en-1-one derivatives (?)- 12 and (?)- 19 . (?)-Conduritol C ((?)- 3 ) was derived in a stereospecific manner from (?)- 12 .     

NMR study of 4-membered rings. VIII—The sign of the four-bond couplings in adducts of cyclopentenone with vic-dichloroethylenes

The proton spectra of the four stereoisomers prepared by photocycloaddition of 2-cyclopentenone to cis and trans dichloroethylene have been analysed using tickling and INDOR techniques in order to obtain the sign of the cross-ring four-bond coupling constants in the cyclobutane ring. These parameters are correlated with the relative orientation of the protons involved. The complete NMR analysis of the seven-spin system of the cycloadduct endo-7-phenoxybicyclo[3.2.0]hept-2-en-6-one has been carried out and all the four-bond coupling constants have been obtained and discussed. The sign of the cross-ring coupling in the cyclobutanone ring has been determined.     

Stereoselective Synthesis of 2,4,6-Trimethylcyclohex-4-ene-1,3-diol Derivatives and of polypropionate fragments with four contiguous stereogenic centers

The Diels-Alder adduct (±)- 3 of 2,4-dimethylfuran and 1-cyanovinyl acetate was converted stereoselectively into benzyl 6-(4-chlorophenylsulfonyl)-1,3-exo,5-trimethyl-7-oxabicyclo[2.2.1]hept-5-en-2-exo-yl ( 26 ) and -2-endo-yl ether ( 36 ). Addition of LiAlH₄ to the latter led to the 3-O-benzyl derivatives 28 and 37 of (1RS,2SR,3SR,6SR)- and (1RS,2SR,3RS,6SR)-5-(4-chlorophenylsulfonyl)-2,4,6-trimethylcyclohex-4-ene-1,3-diol, respectively. Methylenation of 6-exo-(4-chlorophenylthio)-1-methyl-5-methylidene-7-oxabicyclo[2.2.1]heptan-2-one ( 16 ), obtained by reaction of (±)- 3 with 4-Cl-C₆H₄SCl and saponification gave, 6-exo-(4-chlorophenylthio)-1-methyl-3,5-dimethylidene-7-oxabicyclo [2.2.1]heptan-2-one ( 43 ), the reduction of which with K-Selectride afforded 6-exo-(4-chlorophenylthio)-1,3-endo-dimethyl-5-methylidene-7-oxabicyclo[2.2.1]heptan-2-endo-ol ( 44 ). The 3-O-benzyl derivative 48 of (1RS,2RS,3RS,6SR)-5-(4-chlorophenylsulfonyl)- 2,4,6-trimethylcyclohex-4-ene-1,3-diol was derived from 44 via based-induced oxa-ring opening of benzyl 6-endo-(4-chlorophenylsulfonyl)-1,3-endo-5-endo-trimethyl-7-oxabicyclo[2.2.1]hept-2-endo-yl ether ( 49 ). Benzylation of 28 , followed by reductive desulfonylation and oxidative cleavage of the cyclohexene moiety afforded (2RS,3SR,4RS,5RS)-3,5-bis(benzyloxy)-2,4-dimethyl-6-oxoheptanal ( 32 ).     

Zur Lenkung der intramolekularen Diels-Alder-Reaktion von Cyclopentadienen mit olefinischen Substituenten

On the Course of the Intramolecular Diels-Alder-Reaction of Cyclopentadienes with Olefinic Substituents The 1:3 mixture of 4-bromobicyclo [3.2.0]hept-2-en-6-one and -7-one ( 1/2 ), available by N-bromosuccinimide bromination of bicyclo [3.2.0]hept-2-en-6-one, reacted rapidly with the organo-magnesium and -zinc reagents 3, 10a, 10b and 10d by cyclobutanone ring opening and bromide ion expulsion to give the 5-substituted cyclopentadienes 5, 12a, 12b/12c , and 12d as non-isolated intermediates. Further transformation occured in situ either by a direct intramolecular Diels-Alder reaction (path a) or by a [1,5]-H-migration prior to the intramolecular Diels-Alder reaction (path b). The intermediate 5 followed only path a to give the bridged norbornene derivative 7 , the intermediates 12a, 12b and 12c followed only path b to give the annellated norbornene derivatives 15a, 15b and 15c , respectively, and the intermediate 12d followed both paths to give the bridged 14d and the annellated norbornene derivative 15d (in the ration of about 1.4:1). These observations are discussed in terms of the relative velocities of [1,5]-H-migrations and intramolecular Diels-Alder reactions. The major conclusions are: (1) bridged norbornene derivatives with a six-membered ring C (such as 14d ) can be prepared by an intramolecular Diels-Alder reaction from 5-alkenyl-cyclopentadienes 12 , as long as the dienophilic double bond is activated by an appropriate substituent (as in 12d ); (2) such 5-alkenyl-cyclopentadienes 12 are available from the reaction of the bromo-bicyclo-heptenones 1/2 with suitable C-nucleophiles 10 .     

Reduction of bicyclo[3.2.0] hept-2-en-6-one and 7,7-dimethylbicyclo[3.2.0]hept-2-en-6-one using dehydrogenase enzymes and the fungus mortierella ramanniana

Bicyclo[3.2.0]hept-2-en-6-one (1) was reduced with an alcohol dehydrogenase from $\text{Thermoanaerobium brockii}$ and a whole cell system ($\text{M. ramanniana}$) with excellent substrate enantioselectivity: 7,7-dimethylbicyclo[3.2.0]hept-2-en-6-one (2) was similarly reduced using the 3α,20β-hydroxysteroid dehydrogenase from Streptomyces $\text{hydrogenans}$ while $\text{M. ramanniana}$ furnished both 6S-alcohols (4a), (6b) with high optical purity.     

Synthesis of (+)-1,3:2,5-dianhydroviburnitol ((+)-(1R,2R,3S,5R,6S)-4,7-dioxatricyclo[3.2.1.03,6]octan-2-ol)

Epoxidation of (?)-(1R,2R,4R)-2-endo-cyano-7-oxabicyclo[2.2.1]hept-5-en-2-exo-yl acetate ((?)-5) followed by saponification afforded (+)-(1R,4R,5R,6R)-5,6-exo-epoxy-7-oxabicyclo[2.2.1]heptan-2-one ((+)-7). Reduction of (+)-7 with diisobutylaluminium hydride (DIBAH) gave (+)-1,3:2,5-dianhydroviburnitol ( = (+)-(1R,2R,3S,4R,6S)-4,7-dioxatricyclo[3.2.1.0^3,6]octan-2-ol; (+)-3). Hydride reductions of (±)-7 were less exo-face selective than reductions of bicyclo[2.2.1]heptan-2-one and its derivatives with NaBH₄, AlH₃, and LiAlH₄ probably because of smaller steric hindrance to endo-face hydride attack when C(5) and C(6) of the bicyclo-[2.2.1]heptan-2-one are part of an exo oxirane ring.     

Umwandlung von Bicyclo [3.2.0]hept-2-en-6-on in Cyclopentadienessigsäure-Derivate

Conversion of Bicyclo [3.2.0]hept-2-en-6-one into Cyclopentadienylacetic Acid Derivatives The reaction of a mixture of 4exo-bromobicyclo [3.2.0]hept-2-en-6-one ( 2 ) and -7-one ( 3 ) with O- or N-nucleophiles yielded cyclopentadien-5′-yl-acetates 4a–f or-acetamides 4g–h . Due to their rapid isomerization, the products 4 were not isolated, but some of them were demonstrated spectroscopically or captured in situ with maleimide as 10′-substituted norbornene derivatives 7 . The formation of 4 from 2/3 involves a fragmentation of the bond between the carbonyl and the bridge-head C-atom, induced by the attacking nucleophile and the leaving Br-ion and aided by the relief of the four-membered ring strain. Some of the isomerization products of 4 , i.e. the cyclopentadiene-1′-yl- and 2′-yl-acetyl derivatives were captured with maleimide as the 1′- and 8′-substituted norbornene-derivatives 8 and 9 . Two C-nucleophiles did not induce the fragmentation: sodium acetylacetonate substituted the Br-atom and sodium (diethoxyphosphoryl)ethoxycarbonylmethide condensed with the carbonyl group of 2/3 , yielding 11/12 and 13/14 , respectively.     

Solvolysen von 4-Alkylidenbicyclo[3.2.0]hept-2-en-6-olen. Synthese von 1-Vinylfulvenen und 8,8-Diphenylheptafulven

Solvolysis of 4-Alkydenbicyclo[3.2.0]hept-2-en-6-oles. Synthesis of 1-Vinylfulvenes and 8,8-Diphenylheptafulvene Four 4-alkylidenebicyclo[3.2.0]hept-2-en-6-ones 2–5 , obtained via ketene cycloaddition to fulvenes, were reduced to separated mixtures of the ‘endo’ -alcohols ‘endo’- 6 to ‘endo’- 9 (68–73%) and ‘exo’- 6 to ‘exo’- 9 (3–20%). Treatment of some of these alcohols with (CF₃SO₂)₂O in CH₂Cl₂/pyridine caused a spontaneous solvolysis to yield unsaturated 7-membered rings as pyridinium triflates 10–12 or 1-vinylfulvenes 13 and 14 , a new class of reactive tetraenes: Both ‘endo’- 9 and ‘exo’- 9 , having two methyl groups at C(7), were converted into the vinylfulvene 13 (≈ 80%). The alcohols with two H-atoms at C(7) exhibited a stereochemically controlled reaction selectivity, inasmuch as ‘endo’- 6 to ‘endo’- 8 afforded only the corresponding 7-membered-ring pyridinium salts 10–12 (66–79%), while ‘exo’- 6 produced only the vinylfulvene 14 (77%). A stereoelectronic control argument explains the C(1), C(5)-bond cleavage with ‘endo’- B and ‘endo’– 6 -‘endo’- 8 , as well as the C(1), C(7)-bond cleavage with ‘exo’- B , ‘exo’- 6 , and with both ‘endo’- and ‘exo’- 9 . Thermolysis (120°) of the pyridinium triflates 10 and 11 yielded the 3-isopropenyl-cycloheptatrienes 18 and 19 , respectively (≈90%); similar conditions (145°) applied to the triflate 12 produced the doubly cyclized fluorene derivative 21 (60%). When the iodide 22 derived from the triflate 12 with Nal was heated in refluxing toluene, 8,8-diphenylheptafulvene ( 23 , 86%) was obtained.     

Unexpected Configurational and Conformational Preference in Bicyclo [3.2.0]heptane Systems

Einige 7endo-monosubstituierte Bicyclo[3.2.0]hept-2-en-6-one and Bicyclo-[3.2.0]heptan-6-one zeigen eine unerwartete thermodynamische Stabilität gegenüber den entsprechenden 7exo-Isomeren. Die basenkatalysierte Epimerisierung (NaOH oder N(CH2CH3)3) verschiedener 7-monosubstituierter Bicyclo[3.2.0]-hept-2-en-6-one (1-7) und Bicyclo[3.2.0]heptan-6-one (8–10) führt je nach Substituent (R) zu folgenden endo/exo-Gleichgewichtsgemischen: (a) Bicyclo[3.2.0]-hept-2-en-6-one: R = F: 89/11, R = C1: 87/13, R = CH3: 76/24, R = CH2CH3: 65/35, R = CH (CH3)2: 57/43, R= C (CH3)3: 10/90, R= C6H5: 66/34; (b) Bicyclo[3.2.0]-heptan-6-one: R = C1: 85/15, R = CH3: 45/55, R= C (CH3)3: 0,4/99,6. In jedem Fall wurde das gleiche Epimerengemisch erhalten, ausgehend sowohl vom endo- wie auch vom exo-Isomeren. Die bemerkenswerte endo-Stabilität wird einer Bevorzugung der Konformation 11 des Cyclobutanonringes zugeschrieben, verursacht durch geringere Pitzer-Spannung. So kann ein endo-Substituent an C(7) eine pseudoäquatoriale Lage am Cyclobutanonring einnehmen. Bei sehr sperrigen Substituenten mit zunehmender Raumerfüllung nimmt eine 1,2-abstossende Wechselwirkung langsam überhand, bis im Falle des t-Butylsubstituenten die exo-Konfiguration die stabilere wird. Die Dehalogenierung von 7-Halo-substituierten Bicyclo [3.2.0]hept-2-en-6-onen (15 bis 21) mit Zink und Eisessig und mit Tributylzinnhydrid führte zu den folgenden endo/exo-Epimerengemischen der entsprechenden 7-monosubstituierten Bicyclo [3.2.0]hept-2-en-6-one (2 bis 7): R = C1: 92/8, R = CH3: 93/7, R = CH2CH3: 93/7, R = CH(CH3)2: 92/8, R = C(CH3)3: 93/7, R = C6H5: 93/7. In allen Fällen, also unabhängig vom Substituenten R, war das endo-isomere stark bevorzugt. Es muss sich also um eine kinetische Kontrolle im isomerenbestimmenden Schritt handeln: Die Reduktion verläft über das Enolat, bzw. über eine Radikalspezies mit trigonal-planarer Anordnung am C(7), so dass die (irreversible) Wasserstoff-Anlagerung von der weniger behinderten Site, der exo-Seite her erfolgt.     

Synthesis of Polypropionate Fragments Containing Tertiary-Alcohol Moieties. Cross-aldolisations with lithium enolates of 7-oxabicyclo[2.2.1]heptan-2-one derivatives

The Diels-Alder adduct of 2,4-dimethylfuran to 1-cyanovinyl (1′R)-camphanate ((+)-(1R,2S,4R)-2-exo-cyano-1,5-dimethyl-7-oxabicyclo[2.2.1]hept-5-en-2-endo-yl (1′R)-camphanate ((+)- 1 )) was converted into (+)-2,7-dideoxy-2,4-di-C-methyl-L -glycero- ((+)- 6 ) and -D -glycero-L -altro-heptono-1,4-lactone ((+)- 7 ), into (?)-(3R,4R,5R,6S)-3,4:5,7-bis(isopropylidenedioxy)-4,6-dimethylheptan-2-one ((?)- 22 ), and into (+)-(2R,3R,4R,5S,6S)-3,4:5,6-bis(isopropylidenedioxy)-2,4-dimethylheptanal ((+)- 34 ). Condensation of ((+)- 34 with the lithium enolate of (?)-(1R,4R,5S,6R)-6-exo-[(tert-butyl)dimethylsilyloxy]-1,5-endo-dimethyl-7-oxabicyclo[2.2.1] heptan-2-one ((?)- 38 ; derived from (+)- 1 ) gave a 3:2 mixture of aldols (+)- 39 and (+)- 40 (mismatched pairs of a α-methyl-substituted aldehyde and (E)-enolate) whereas the reaction of (±)- 34 with (±)- 38 gave a 10:1 mixture of aldols (±)- 41 and (±)- 39 . A single aldol, (?)- 44 , was obtained to condensing (+)- 34 with the lithium enolate of (+)-(1S,4S,5S,6S)-5-exo-(benzyloxy)-1,5-endo-dimethyl-7-oxabicyclo[2.2.1]heptan-2-one ((+)- 43 ; derived from (?)-(1S,2R,4S)-2-exo-cyano-1,5-dimethyl-7-oxabicyclo[2.2.1]hept-5-en-2-endo-yl (1′S)-camphanate ((?)- 3 )). All these cross-aldolisations are highly exo-face selective for the bicyclic ketones. The best stereochemical matching is obtained when the lithium enolates and α-methyl-substituted aldehydes can realize a ‘chelated transition state’ that obeys the Cram and Felkin-Anh models (steric effects). Polypropionate fragments containing eleven contiguous stereogenic centres and tertiary-alcohol moieties are thus prepared with high stereoselectivity in a convergent fashion. The chiral auxiliaries ((1R)- and (1S)-camphanic acid) are recovered at the beginning of the syntheses.     

A bicyclo[3.2.0]hept-3-en-6-one approach to prostaglandin intermediates

[reaction:see text] The substituted cyclopentanic structures, 6-benzyloxymethyl-7-hydroxy-2-oxabicyclo [3.3.0]octan-3-one (1), a Corey lactone derivative, and 6-exo-benzyloxymethyl-2-oxabicyclo[3.3. 0]oct-7-en-3-one (2), have been obtained stereoselectively through the bicyclo[3.2.0]hept-3-en-6-one approach via 5-benzyloxymethyl-3-hydroxy-6-heptenoic acid, easily accessible from the inexpensive monoprotected cis-2-butene-1,4-diol.     

Metal-free diastereoselective synthesis of diaza-bicyclo[3.2.0]heptan-7-one and its transformation to functionalized proline esters

A metal-free diastereoselective synthesis of novel 4-halo-3,6-di-aryl-2,6-diaza-bicyclo[3.2.0]heptan-7-one by intramolecular endo-trig haloamination of 3-amino-2-azetidinone is reported. The amidiolytic ring opening of diaza-bicyclo[3.2.0]heptan-7-one with sodium methoxide provides an easy access to previously unknown 4-halo-3-aryl amino-pyrrolidine-2-carboxylic acid methyl esters in good yields.     

Enantiomerically pure 7-oxabicylo[2.2.1]hept-5-en-zyl derivatives as synthetic intermediates. Part III. Total synthesis of D- and L-ribose derivatives

Enantiomerically pure methyl 5-bromo-5-deoxy-2,3-O- isopropylidene-β-D - (D - 5b ) and -β-l-ribofuranoside (l- 5b ) have been derived from (?)-(1R,2S,4R)-2-exo-cyano-7-oxabicylo[2.2.1]hept-5-en-endo,-yl (1′S)-camphanate ( 1 ) and (+)-(1S,2R,4S)-2-exo-cyano-7-oxabicyclo[2.2.1]hept-5-en-2-endo-yl(1′R)-camphanate ( 2 ), respectively, in 5 synthetic steps and 28% overall yield. Hydrolysis of D-5b and L - 5b afforded methyl 2,3-O isopropylidene-β-D -ribofuranoside (D -5a) and methyl 2,3-O-isopropylidene β-L-ribofuranoside (L-5a), respectively. The intermediate (+)-(1R,4R,5R,6R) 5-exo,6-exo-(isopropylidenedioxy)- 7 -oxabicyclo[2.2.1]heptan-2-one ((+)- 7 ) and its enantiomer(–)-7 were also obtained enantiomerically pure by resolution of (=)- 7 by the Johnson-Zeller method. In bothe approaches, the chiral auxiliaries ((–)- and (+)-camphanic acids, or (+)-(S)-N,S-dimethyl-S-phenylsulfoximide) were recovered at an early stage of the synthesis.     

Copper(I)- and Copper(II)-catalyzed Diels-Alder Additions of α-Substituted Acrylonitrile to Furan. The Synthesis of 7-Oxa-bicyclo[2.2.1]hept-5-en-2-one

The difficult Diels-Alder additions of α-acetoxy- and α-chloroacrylonitrile to furan can be run at 20–35° and atmospheric pressure in the presence of CuCl. Cu(BF₄) · 6 H₂O, Cu(OOCCH₃)₂ · H₂O or cupric tartrate · 3H₂O. Under kinetic control, the exo-carbonitrile adducts 2 and 8 , respectively, are favoured. Saponification of the 2endo-acetoxy-7-oxabicyclo[2.2.1]hept-5-ene-2exo-carbonitrile ( 2 ) furnished the 7-oxabicyclo[2.2.1]hept-5-en-2-one ( 4 ). Basic hydrolysis of the adducts ( 8 + 9 ) of α-chloroacrylonitrile to furan and its 5exo, 6exo-isopropylidenedioxy derivatives did not give the corresponding ketones, the carboxamides 14 + 15 and 16 + 17 , respectively, were isolated.     

A simple and efficient synthesis of enantiomeric (3aRS,4RS,6aSR)-4-hydroxy-3,3a,4,6a-tetrahydro-1H-cyclopenta[c]furan-1-ones

Diastereomeric amides produced via the cleavage of easily available (±)-7,7-dichloro-4-exo-trimethylsilylbicyclo[3.2.0]hept-2-en-6-one by treatment with (+)-α-methylbenzylamine were transformed into bicyclic lactam-aminals, which can easily be separated by column chromatography on SiO₂. The latter products lead to enantiomeric (3a,6a)-4-hydroxy-3,3a,4,6a-tetrahydro-1H-cyclopenta[c]furan-1-ones after the removal of the chiral auxiliary and epoxidation.     

The Diels-Alder Reactivity of 2,2′-Ethylidenebis[3,5-dimethylfuran] and Exploratory Chemistry of the Mono-adducts

In the presence of Me₃Al, 1-cyanovinyl acetate added to 2,2′-ethylidenebis[3,5-dimethylfuran] ( 1 ) to give a 20:10:1:1 mixture of mono-adducts 4,5,6 , and 7 resulting from the same regiocontrol (‘para’ orienting effect of the 5-methyl substituent in 1 ). The additions of a second equiv. of dienophile to 4–7 were very slow reactions. The major mono-adducts 4 (solid) and 5 (liquid) have 2-exo-carbonitrile groups. The molecular structure of 4 (1RS,1′RS,2SR,4SR)-2-exo-cyano-4-[1-(3,5-dimethylfuran-2-yl)ethyl-7-oxabicyclo[2.2.1]hept-5-en-2-endo-yl acetate) was determined by X-ray single-crystal radiocrystallography. Mono-adducts 4 and 5 were saponified into the corresponding 7-oxanorbornenones 8 and 9 which were converted with high stereoselectivity into (1RS,1′SR,4RS,5RS,6RS)-4-[1-(3,5-dimethyl furan-2-yl)ethyl]-6-exo-methoxy-1,5-endo-dimethyl-7-oxabicyclo [2.2.1]heptan-2-one dimethyl acetal ( 12 ) and its (1′RS-stereoisomer 12a , respectively. Acetal hydrolysis of 12a followed by treatment with (t-Bu)Me₂SiOSO₂CF₃ led to silylation and pinacol rearrangement with the formation of (1RS,1′RS,5RS,6RS)-4-[(tert-butyl)dimethy lsilyloxy]-1-(3,5-dimethylfuran-2-yl)ethyl]-5-methoxy-6-methyl-3-methylidene- 2-oxabicyclo[2.2.1]heptane ( 16 ). In the presence of Me₃Al, dimethyl acetylenedicarboxylate added to 12 giving a major adduct 19 which was hydroborated and oxidized into (1RS,1′RS,2″RS,3″RS,4SR,4″RS,5 SR,6SR)-dimethyl 5-exo-hydroxy-4,6-endo-dimethyl-1-[1-(3-exo,5,5-trimeth oxy-2-endo,4-dimethyl-7-oxabicyclo[2.2.1]hept-2-yl)ethyl]-7-oxabicyclo [2.2.1]hept-2-ene-2,3-dicarboxylate ( 20 ). Acetylation of alcohol 20 followed by C?C bond cleavage afforded (1′RS,1″SR,2RS,2′″SR,3RS, 3″SR,4RS,4″SR,5RS)-dimethyl {3-acetoxy-2,3,4,5-tetrahydro-2,4-dimethyl-5-[1-(3-exo,5,5-trimethoxy ?2-endo,4-dimethyl-7-oxabicyclo[2.2.1]hept-1-yl)-ethyl]furan-2,5-diyl} bis[glyoxylate] ( 24 ).