Alkynes, oxetanes

The stereoselective synthesis of unsaturated oxetanes has recently been achieved by Feigenbaum and coworkers.Previous studies have indicated that photochemical cis-trans isomerization of enals is rapid and results in the formation of equivalent amounts of stereoisomeric alkene adducts. " For example, irradiation of rran.r-crotonaldehyde and 2,6-dimethylfuran produced a 1 1 mixture of alkenic isomers (174) and (175) in 64% yield. Irradiation of 4-trimethylsilylbutyn-2-one and furan provided with S 1 stereoselectivity the bicyclic oxetane (176) in which the methyl group occupies the exo position, presumably because of the small steric requirement of the triple bond. Desilyation of the protected al-kyne produced an alkynic oxetane which was hydrogenated under Lindlar conditions to bicyclic vinyl-oxetane (177) attempts to use the unprotected butyn-2-one gave low isolated yields of oxetane because of extensive polymerization. The stereochemical outcome thus broadens previous alkynyloxetane syn-theses and makes possible the preparation of new oxetane structures that may be synthetically useful. 

Preliminaiy investigations describing the photoadditions of ynones to alkenes have determined tiiat these species may react through n, n excitation to produce alkynic oxetanes. Irradiation of 3-butyn-2-one with isobutene gave a 46% isolated yield of (72) and (74) (14 86). 3-Octyn-2-one analogously provided a 50% isolated yield of (73) and (75) (15 85), a regioselectivity predicted on the basis of the best diradical intermediate. 

A mechanistic scheme involves intramolecular single-electron transfer (SET) from the enamino moiety toward carbon 5 of the ring, and subsequent transannular interaction in zwitter-ionic biradical 259 with formation of stabilized zwitter-ion 260. Opening of the oxetane ring in 260 leads to cyclobutene 256, while secondary photolysis of the latter gives olefin 257 and alkyne 258 (Scheme 100). 

In sharp contrast to silylformylation of alkynes, specific combination [Rh(GOD)Gl]2/THF of catalyst precursor and solvent is quite important for selective silylformylation of aldehydes. Go-use of A-methylpyrazole is crucial to perform silylformylation of epoxides ( [Rh(GO)2Gl]/GH2Cl2 " and oxetanes [Rh(GO)2Gl]2/toluene. ... 

The (n,n excited state of a ketone has electrophilic character, similar to that associated with alkoxy radicals, and it is not surprising that these excited states readily attack carbon-carbon multiple bonds. The overall reaction that normally ensues is a cycloaddition, giving a four-membered oxygen heterocycle—an oxetane from an alkene addend (4.62), or an oxete from an alkyne addend (4.63). Some oxetanes are of interest in their own right, but many are useful intermediates in the synthesis of other compounds. 

Oxetanes can be formed by intramolecular reaction between a carbonyl group and an alkene, and this has been used (4.74) in making analogues of thromboxane A, (one of the compounds responsible for the control of blood clotting), albeit usually as the minor product. A special case of intramolecular reaction is seen for a,p-unsaturated carboxylic acids 14.75), where the product is an oxete that is tautomeric with a p-lactone. Oxetes may also be formed by photocycloaddition of ketones or aldehydes with alkynes the oxete normally ring-opens at room temperature to give an a,p-unsaturated carbonyl compound (4.76), but at lower temperatures its spectral... 

Oxetenes (oxets) have been postulated as primary photoadducts between carbonyl compounds to alkyl- and aryl-substituted alkynes and alkylthio-acetylens [66]. The first evidence for an unstable intermediate with a lifetime of several hours at — 35 °C was reported for the benzaldehyde 55/2-butyne-photoproduct 76 [67]. On further irradiation in the presence of excess benzaldehyde, a Z /s-oxetane 77 was formed (Sch. 21). 

Numerous papers have been published describing the photochemical production of enones from carbonyl compounds and alkynes. The first detection of an oxetene intermediate involved low-temperature (-78 C) photolysis of 2-butyne and benzaldehyde to form the photoproduct (61), which was observed by NMR. The oxetene undergoes further photoreaction with benzaldehyde to form the novel fused oxetane (62). Recently, Friedrich has reported Either studies on the reactivity of oxetenes and developed alternative syntheses of the parent compound and 3-phenyloxete (64). The parent oxetene is found to have a thermal half-life of t proximately 8 h in solution at room temperature. The phenyl-substituted derivative (64) underwent slow ring-opening under acidic conditions to form 2-phenylprq)enal and air oxidation to yield a formate derivative, probably via a radical process. 

Bos and coworkers have developed several applications of alkyne-ketone photoadditions to organic synthesis. 2 Irradiation of a solution of acetone and 1-methylthio-l-propyne gives as a major product the cycloadduct (67) this results from selective oxetane formation due to radical stabilization by the methyl-thio group, followed by electrocyclic ring opening. Similarly, photoreaction of benzil and 1-t-butylthio-1-propyne gave the adduct (68) in 45% yield, which was transformed in 90% yield to the furan (69). 

Excited states undergo reaction at the C=0 bond to give oxetanes, whilst (7r,7r ) states react at the C=C bond to give cyclobutanes. In a similar way.p-quinones and alkynes on irradiation give quinone methides (equation 91) if the quinone has a... 

The fourth type of reaction with alkynes involves only cyclic bis-keto-ylides. Thus, the indanedione ylide (2) reacted with acetylenedicarboxylic ester to afford the new ylide (51), the result of an overall addition and oxygen transfer. Enolate anion attack on the triple bond, followed by oxetan ring formation and reopening, was proposed to account for the reaction, which was observed with several different ylides. 

Photo-induced addition reaction of aromatic carbonyl compounds with alkynes gives unstable oxetanes. For example, the reaction of benzaldehyde with 2-butyne 138 gives a,(3-unsaturated carbonyl compound 139 by cleavage of intermediate oxetane [80]. 

In addition, the Louie and Aissa groups reported similar transformations by activation of Boc-protected azetidinone (a recent DFT calculation suggests an alternative oxidative addition mechanism for the alkyne insertion into azetidinones [48]) and/or 3-oxetane as the coupling partner [49, 50]. A [4+2] coupling between protected azetidinones and internal alkynes was independently reported by the Louie [51] and Murakami groups [52]. As shown in Scheme 11, protected azetidinone (58) and internal alkynes (59) can undergo oxidative metallocyclization to afford the sterically more favored intermediate 61b, which will afford the... 

In the presence of catalytic amount of Cu(NCMe)4NTf2 (4 mol %), 4-methoxypyridine A -oxide (2 equiv) promotes the oxidative cyclization of alkynyl oxiranes and oxetanes (eqs 15 and 16). The mild reaction conditions tolerate a breath of functional groups such as distal epoxides, alkynes, ethers, acetamide, tosylamide, and aryl halides. 

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