Oxetane ring contraction

The oxetane tertiary amides 15 on treatment with methyl triflate in anhydrous nitrobenzene at 150 °C undergo ring expansion to the cyclic acetals 16 and, if the groups R and R2 are sufficiently bulky, the acetals undergo a ring contraction to form the azetidines 17 . 

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). 

The oxetane /-amides 222 undergo a ring expansion-contraction sequence in the presence of a Lewis acid to azetidine derivatives 223 (Equation 60) <2000JOC2253>. The overall reaction sequence has been described as double isomerization . The four-membered oxetane ring first enlarged to a [2.2.2]-dioxazabicycle, which in turn rearranged to the final azetidine derivatives. 

A generally applicable oxetane synthesis (e.g., 100 101) can be achieved by the anionic ring contraction of cyclic acetals fused to butanolide using organolithium reagents (Scheme 53) <2004SL651, CHEC-III(2.05.10.2)352>. 

Alkyllithium compounds have been used to induce a new anionic ring contraction proceeding by a complex mechanism involving carbenes and illustrated by reaction of a furan-fused 1,3-dioxolane to form the oxetane product (Equation 22) <2004SL651>. 

Oxetane ring from 2-ethylenealcohols with ring contraction... 

The base-catalysed ring-contraction of 5-lactone 2-triflates to homochiral tetrahydrofurans (Vol. 26, p. 169) now has a complementary acid catalysed procedure, as exemplified by the conversion of 23 to 24, and of 25 to 26, on treatment with HQ in methanol at room temperature. Under these conditions, the triflate 27 gave the expected product, but with K2CO3 in MeOH the bicyclic oxetane 28 was obtained in 86% yield, a result rationalized by a mechanism involving initial P-elimination fiom 27. Cyclic sulfates can also be used to make anhydroaldonic acids, as... 

SCHEME 4.12 Oxetane formation by ring contraction of aldonolactones. 

Xylonolactone 95, embodying an azide functionality, was submitted to the ring contraction conditions to determine whether it was possible to access 5-azidooxetanes in a smaller number of steps 5-azido oxetanes (Scheme 4.15). While 96 was obtained in a 67% yield, ring contraction of its epimer 98 afforded a mixture of the a and p anomers isolated in a 57% yield for 99 and a 7% yield for 101. Azide reduction and ester hydrolysis afforded Boc protected 8-amino acids in a good yield [37]. 

---