Lactones ring contraction

Selective silylation of aldohexono-1,4-lactones with tert-butylchlorodi-methylsilane gave the 2,6-di-O-silylated derivatives as major products (40). However, D-glucono-1,5-lactone underwent ring-contraction during silylation to give 2,6-di-O-terl-butyldimethylsilyl-D-glucono-1,4-lactone (31a) together with its 5,6-di-O-silyl isomer (31b), in 65 and 18% yields, respectively. 

The 2-trifluoromethanesuIfonates of the four diastereomeric 3,5-di-O-benzyl-pentono-1,4-lactones (such as D-ribono-1,4-lactone, 283) gave, upon treatment with potassium carbonate in methanol, the ring-contraction product, methyl oxetane-2-carboxylate (284). The stereochemistry at C-2 of the resulting oxetanes is determined by the configuration at C-3, rather than C-2, of the starting lactones (267). 

Methyl oxetane-2-carboxylate derivatives (e.g., 284), obtained by ring contraction of aldonolactones, have been employed for the synthesis (279) of the nucleoside / -noroxetanocin [9-(/ -D-eryt/iro-oxetanosyl)adenine, 304] and its a-anomer via an a-chloride obtained by a modified Hunsdiecker reaction. Displacement of chloride by adenine and debenzylation gave 304. The threo isomer of304, /J-epinoroxetanocin (305), was likewise synthesized from D-lyxono-1,4-lactone. The oxetane nucleosides display potent antiviral activity against the human immunodeficiency virus (HIV). 

Oxygen- and sulfur-assisted methods have been described to synthesize strained macrolactams by ring contraction through attack of the amine on the intermediate macro(thio)lactone [37]. 

Ring contraction of readily available sugar derivatives has been used in synthetic approaches towards C-nucleosides, and the first ring contraction under acidic conditions of benzylated 2-bromo-2-deoxy-1,5-lactones to give... 

A wide range of acetal-protected aldono-1,5-lactones ready for preparing C-2 activated aldonolactones has been published [115] and used for preparation of highly functionalized tetrahydrofurans. The ring contractions were... 

Other ring contractions that give azapentalene derivatives include the rearrangement of a fused oxazine to a pyrazolo[l,5-a]indol-4-one with acetic anhydride,165 and an interesting photochemical contraction of a cyclic lactone, which produces an isomeric fused indolone by a mechanism thought to involve the first meta photo-Fries rearrangement [Eq. (19)].166 The product was used as an intermediate for the synthesis of mitomycin antibiotics (Section VI,A). 

The enantiopure (A)-(+)-6-amino-l,3-oxazepan-4-one 29 was obtained in 35% yield by acid-catalyzed condensation of 28 (obtained in two steps from natural asparagine) with dimethoxypropane (Equation (3) see also Section 13.08.3.1). This reaction, which was very sensitive to both reaction conditions and the nature of the acid catalyst, was shown to proceed via the amide 30. Further reaction of 28 under forcing conditions (heating in toluene with />-toluenesulfonic acid) resulted in ring contraction to lactone 31 <1999H(51)365>. 

E is facile. Dehydrochlorination provides the aromatic products 233. An alternatively possible HC1 elimination/electrocyclization/decarboxylation pathway was excluded, since lactone 230B was thermally stable under the reaction conditions in the absence of the catalyst. (NHC)Cu(I) catalyst 232 gave comparable or better yields than 231 in these ATRC/ring contraction sequences, while other (NHC)Cu(I) complexes provided considerably lower yields [320]. Chlorinated cyclic compounds arising from ATRC can also be transformed to chlorinated furans [321]. 

While the condensation of enamine 37 with methyl OY7 s-2-butenoate, followed by acid hydrolysis and sodium borohydride reduction affords lactone 38 with reasonable efficiency, the cyclodehydrative ring contraction of this intermediate with PPA gives a mixture of bicyclo[3.3.0]octenones in abysmal (< 5 %) yield.66 To circumvent this difficulty and enable the large scale production of 39,2-carbo-methoxy-4,4-dimethylcyclohexanone was initially transformed to tram diacid 40 under Favoiskii conditions (Scheme 14). Conversion to the diacid chloride and condensation with lithium dimethylcuprate resulted in formation of the diacetyl derivative. In basic solution, the latter is reported to experience epimerization and aldol cyclization with dehydration in 82 % yield. With hydrogen and palladium on charcoal, the essentially quantitative production of 39 was achieved.66 ... 

A-Protected 7-amino-8-hydroxyoctenoic acids were cyclized to their corresponding nine-membered ring lactones (Scheme 38, Section 14.01.5.2). Subsequent hydrogenation of the double bond using Pd/C in MeOH afforded the saturated lactone 95, which underwent intramolecular O-to-A-acyl (lactone-to-lactam) ring contraction to 8-hydro-xymethyl-6,7-dehydro-2-azocanone 197 (Scheme 83 <1998TL9309>). 

The Baeyer-Villiger oxidation has been utilized as an element of several novel functional group manipulations. Suginome and Yamada converted adamantanone (64) to 2-thiaadamantane (66) via the lactone (65 Scheme 19). Eaton et al.P in the synthesis of pentaprismane (70) from homopentaprismanone (67 Scheme 20), required that a leaving groiq) be introduced a to the carbonyl group in or r to carry out a Favorskii ring contraction. Oxidation of (67) afforded lactone (68), which was converted in several steps to the requisite hydroxy ketone (69). 

Whereas empirical force-field calculations predict a ring A boat conformation for lanost-8-en-3-one, combined empirical force-field-extended Hiickel molecular orbital calculations favour a ring A chair conformation. Europium-shift n.m.r. results indicate that the molecule adopts the latter conformation. Studies on the peracetic acid-boron trifluoride etherate Baeyer-Villiger oxidation of 4,4-dimethyl-3-keto-triterpenoids to 5-lactones (18) and their subsequent ring contraction to y-lactones have been reported. Dehydrogenation of lanost-8-en-3j8-ol with 2,3-dichloro-5,6-dicyanobenzoquinone afforded, in addition to the corresponding 7,9(1 l)-diene, the aromatic seco-lanostane derivatives (19)... 

---