With oxetanes

Synthesis of paclitaxel and resiniferatoxin analogs, diterpenoids with oxetane fragments 97G461. 

Grignard reagents react with oxetane, a four-membered cyclic ether, to yield primary alcohols, but the reaction is much slower than the corresponding reaction with ethylene oxide. Suggest a reason for the difference in reactivity between oxetane and ethylene oxide. 

Another new modification is the 2 -deoxy-2 flouro-Darabinonucleic acid (2 F-ANA), which increases the strength of the oligonucleotide-mRNA hybrids, elicits efficient RNaseH-mediated degradation of the target, is more nuclease resistant and reaches high intracellular concentrations for prolonged time. Similar results could be obtained with oxetane modified ASONs. 

Oxetanes are significantly less reactive with nucleophiles due to diminished ring strain. Under certain conditions, however, amines can open oxetanes to give amino alcohols. tert-Butylamine reacts with oxetanes in the presence of Yb(OTf)3 to give 3-hydroxy amines. Lithium tetrafluorohorate has also been used for this... 

SPOCC resin is based on the cross-linking of long-chain Poly(ethylene glycol) (PEG)terminally substituted with oxetane by cationic ring-opening polymerization. 

If the olefin bears easily abstractable hydrogens, this reaction can also compete with oxetane formation and the resulting radical coupling products will predominate. This competition can be expressed as a ratio of yields of addition products to abstraction products (A add/A abs), and will be different for each pair of reactants. This ratio is delicately balanced, and seemingly small changes in the structure of either starting material can shift the predominant reaction. 

Dichlorine heptoxide, which can be a powerful oxidizing agent, reacts with oxetane in carbon tetrachloride solution at 0°C to give a fair yield of propane-1,3-diperchlorate (equation 38). It was suggested that the mechanism involved formation of a per-chlorooxetanium ion, which subsequently reacted with perchlorate ion (75JOC81). 

The reaction of oxetanes with Grignard reagents and organolithium compounds is well known and has been useful, particularly with oxetane itself. A recent application involves use of the reaction of isopentylmagnesium bromide with oxetane as the first step of a synthesis of an insect pheromone (equation 43) (76CB3375). The Grignard reaction with 2-methyloxetane and 2-phenyloxetane is less satisfactory, due to the extensive formation of by-products. 

Carbonylcarbene reacts with oxetane in a complex manner, giving cyclopropane and propene by a deoxygenation process and ketene plus ethylene as apparent insertion-fragmentation products (equation 66). The reaction is carried out by irradiation of a solution of carbon suboxide in oxetane under these conditions, photodecomposition of intermediates is possible. The initial attack is believed to be at the ring oxygen atom to give a zwitterionic species (78JA6425). 

The use of oxetanes has been also explored. Both primary and secondary aliphatic amines react with oxetanes, under C02 (4MPa), at 373-393 K, in the absence of any catalyst, to afford monocarbamates of 1,3-propanediols, together with amino alcohols as side products [84]. 

The perbenzylated a-glycosyl iodides are thought to react with oxetane via the mechanisms shown in Schemes 21 and 22 (where R=PhCH2).138 The amount of the -product increases as the reaction temperature decreases. In fact, at — 60 °C, the fi a ratio in the product from the perbenzylated derivatives of galactosyl, mannosyl, and glucosyl iodides ranges from 10 1 to 50 1, indicating that the reaction in Scheme 21 is faster than that in Scheme 22. 

Unlike ethylene oxide, oxetane reacted very slowly with the alkaloid imine derivatives to afford low yields of tetrahydro-l,3-oxazine derivatives. Treatment of veatchine azomethine acetate (10) with oxetane in acetic acid at 50° afforded the six-membered carbinolamine ether, homoveatchine acetate (220), in 25% yield. The latter was isolated as a mixture of C-20 epimers. 

Grignard reagents react slowly with oxetane to produce primary alcohols. Propose a mechanism for this reaction, and suggest why oxetane reacts with Grignard reagents even though most ethers do not. 

To make ethers more reactive, they must be complexed with strong Lewis acids. BF3 is commonly used with cyclic ethers, and even with epoxides it increases the rate and yield of the reaction when organometallic reagents are used as nucleophiles. BF3 is most easily handled as its complex with diethyl ether, written BF3 OEt, BuLi does not react with oxetane, for example, unless a Lewis acid, such as BF3, is added, when it opens the fouremembered ring to give a quantitative yield of H-heptanoI. 

Reactions of Grignard reagents with oxetane lead to three-carbon homologation yields are often good, but 3-halogenopropanol may be a significant by-product [37] ... 

Polymerization of 2-oxa-6-thio (3.3) spiroheptane at 270 K yields a soluble crystalline polymer with oxetane rings... 

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