Cyclobutanol derivatives

Another convenient method for the preparation of functionalized cyclobutanol derivatives is by treatment of 1,2-diphenylethylene acetals containing a 1,3-dithiane moiety in the y-position, e.g. 14c. with butyllithium. The isolation of 2,2-(propane-l,3-diyldisulfanyl)cyclobutanol (15c) together with benzyl phenyl ketone in 90 and 92 % yield, respectively, indicates that the reaction mechanism should involve the intramolecular attack of the metalated dithiane on the acetal carbon atom with concomitant hydride shift at the acetal group.15... 

An esoteric attempt to synthesize cis-dianthrylethylene 38a via the cyclobutanol derivative 128 involved as starting material l,2-di-9-anthrylethanol 127, which was reportedly formed in good yield in a one-pot reaction by lithium aluminum hydride reduction of 9-anthraldehyde 129. Again, we had to abandon this route to cis-dianthrylethylene when the dianthrylethanol of the literature was found to be the 9,10-dihydroanth-racene derivative 130. However, dianthrylethanol 130 did form the acetate 131, which upon treatment with base afforded, via elimination product 114, hydrocarbon 113, viz. lepidopterene [147], whose structure, fortunately, had been established in 1975 [129,130]. 

Irradiation of the phenethyamine salt 58 in the solid state gave the chiral cyclobutanol derivative 59 of 97% ee [31]. 

Scheffer et al. provided another unimolecular asymmetric transformation involving the Norrish type II reaction, a well-known excited state process of ketones that is initiated by an intramolecular hydrogen atom transfer from carbon to oxygen through a six-membered transition state (Scheme 5). [19a] An adamantyl ketone derivative 27 was found to crystallize from ethanol in very large prisms in the chiral space group P2 2 2. Upon irradiation of these crystals to approximately 10% conversion, the chiral cyclobutanol derivatives 28 were afforded as the major products in 80% ee. 

Zucco, M. Le Bideau, F. Malacria, M. Palladium-catalyzed intramolecular cyclization of vinyloxirane. Regioselective formation of cyclobutanol derivatives. Tetrahedron Lett. 

Sml2 is used for the preparation of a cyclobutanol derivative (94) from a-formyl a,(3-unsaturatedester (93), via4-exo-trig ring closure ofthe formed ketyl radical (eq. 3.34b). 

To the solution of Sml2 (0.1 M, 1.0 mmol) in a mixture of THF (10 ml) and MeOH (2.5 ml) at 0 °C under a nitrogen atmosphere was added aldehyde (100 mg, 0.5 mmol) in THF (2 ml). After the mixture was stirred for 2 h at 0 °C, sat NaCl aq. solution (2 ml) and citric acid (128 mg, 0.61 mmol) were added to the mixture, and the organic layer was extracted with ethyl acetate three times. After the organic layer was dried over Na2S04, the solvent was removed. The residue was chromatographed on silica gel (eluent ethyl acetate /hexane = 3/7) to give 67 mg of a cyclobutanol derivative in 65% yield as an oil [111]. 

Scheme 5.16 Yang cyclization leading to cyclobutanol derivatives and p-lactams.

In addition to these, a third reaction has been identified recently (15) which results in the formation of a cyclobutanol derivative ... 

No cyclobutanol derivative was formed. It was proposed that the degenerate cyclopropylcarbinyl rearrangement proceeded via the bicyclobutonium ion [127]. 

Lipase-catalyzed asymmetric hydrolysis has also been conducted on numerous monocyclic, variously substituted five-, six-, and seven-membered cycloalkane and cycloalkene secondary alcohols and diols. More recent reports include cis-4-acetoxyflavan, substituted cyclopentenones, and the 1,2-bis(hydroxymethyl)cyclobutanol derivative exemplified in eq 3. ... 

An exception involves the passage of hot alcohol vapors over thorium oxide at 350-450°C, under which conditions Hofmann s mle is followed, and the mechanism is probably different. Cyclobutanol derivatives can be opened in the presence of a palladium catalyst. 2-Phenylbicyclo[3.2.0]octan-2-ol, for example, reacted with a catalytic amount of palladium acetate in the presence of pyridine and oxygen to give phenyl methylenecyclohexane ketone. ... 

The Kunz group used a variety of sugar derivatives as chiral auxiliaries for the [2+2] cycloadditions of ketenes and enol ethers, which produced eventually highly substituted cyclobutanol derivatives [73]. 

Hydrogen Transfer - The typical reaction of this type is exemplified by the conversion of the arylketones (23) into the cyclobutanol derivatives (24) and (25)... 

Norrish Type II reactivity is often a common reaction path for ketones with available Y 7< °sens. Hydrogen abstraction by the excited carbonyl group results in the formation of a 1,4-biradical which can undergo either bond cleavage to reform the carbonyl group and an alkene or bond formation to yield a cyclobutanol derivative. The fragmentation path is followed by the ketone (13). The interest in this reaction is the control which can be exercised on the ketonization of the resultant enol (14). Apparently in the presence of (->-ephedrine asymmetric formation of the final product, (R)-2-methylindanone (15),... 

The low quantum yield indicates that intermediate complexes and diradicals decay unproduc-tively. In general, Norrish type II photoreactions and other hydrogen abstraction processes must be overcome in order to achieve successful cycloaddition. Only in a few reported cases is intramolecular hydrogen abstraction a serious competitive reaction path. For example, the cycloheptenyl-substituted ketone 5 yields an oxetane 6 in addition to a cyclobutanol derivative 758, whereas the unsaturated cycloheptanone 8 only gives oxetane products 9 and 10 on irradiation59. The main product 10 was converted in two steps to azulene in 25 % overall yield. The reaction sequence 11 - 12 - 13 also demonstrates the high synthetic potential of the intramolecular Paterno-Biichi reaction61. 

Both cyclobutanones and the tertiary cyclobutanols derived from them behave as intramolecular alkylating reagents towards 0-substituted aromatic rings under 4-TsOH catalysis yielding cyclobuta[c]chromans 23. The use of an equimolar amount of 4-TsOH results in subsequent fission of the cyclobutane ring and the formation of chromenes <04T449>. 

An enantioselective semipinacol rearrangement has been reported. For example, the cyclobutanol derivative (184) reacts with an iodonium source (186) to provide the rearrangement product (185) in good yield (Scheme 39). In the presence of a chiral phosphoric acid, good chrial induction is obtained in product formation. The key steps in this conversion involve facial selectivity of iodonium attack and stereocontrol of the Wagner-Meerwein rearrangement step (187). Both steps are thought to be controlled by the chiral counterion. 

Chiral cyclopropanes, such as (9), have been obtained by degradation of (+)-a-pinene using a sequence of reactions that features a stereocontrolled ring contraction of a cyclobutanol derivative/ The iron carbonyl complex (10) has been resolved, and used to prepare the optically active cyclopropanes (11)."... 

The reaction of the four-membered ring eneamide 196 with dichloroketene provides the unstable [2+2] cycloadduct 197, which on reduction with NaBltt in THF affords the cyclobutanol derivative 198 in a combined yield of 54 %... 

Few aliphatic ketones can photorearrange to cyclobutanol derivatives. This reaction does not appear to be an important process during the photolysis of aliphatic ketones. Both Norrish Type I and Type II reactions are very important in the mechanism of photodegradation of polymers containing carbonyl (CO) groups (cf. section 3.2.1). 

A third primary process was also observed in ketone photoly b (61, 69) this results in the formation of a cyclobutanol derivative. This reaction, however, was recognized in only a few of the ketones studied. The last primary reaction to be considered is the excitation of the carbonyl group to the biradical triplet state (5) and subsequent intermoelcular hydrogen abstraction from the substrate RH with formation of free radicals... 

Two-carbon ring expansions of the five-, six,- and seven-membered rings of P-indanone, P-tetralone, and P-suberone can be achieved via a sensitized [2-1-2]-photoaddition of the trimethylsilyl enol ethers of the cyclic ketones with acrylonitrile or methyl acrylate followed by P-fragmentation of the alkoxyl radicals generated from the hypoiodites of the resulting cyclobutanols and mercury(ll) oxide-iodine, as outlined in Scheme 72. The ring expansion of the cyclobutanol derived from P-indanone enol ether and acrylonitrile gave an a,P-unsaturated nitrile. 

The photolysis of the hypoiodites of cyclobutanols derived from the [2+2]-photoadducts of 3-hydrox-yquinolin-2(lH)-one with alkenes induced P-fragmentation at the outer bonds of the corresponding cyclobutanoxyl radicals to give furo [2,3-c] quinolin-4(5H)-ones in 5 to 50% yields with an accompanying formation of products arising from a ring expansion, as outlined in Scheme 74. ... 

The photolysis of the hypoiodite generated from a cyclobutanol derived from the [2-1-2]-photoaddition of 4-hydroxy-1(2H)-isoquinolinone with an electron-deficient alkene in the presence of mercury(ll) oxide and iodine resulted in a (3-scission at the ring-fusion bond of the cyclobutanoxyl radical to give a 3,6-epoxybenzazocinone derivative in 76% yield (Scheme 75). A weaker aromatic stabilization and destabilization by the cyano substituent in the carbon-centered radical arising from a fragmentation at the non-fusion bond led to ring expansion. 

The photolysis of the hypoiodites generated from the cyclobutanols, derived from the [2-l-2]-photo-addition of 2-hydroxynaphthoquinone with alkenes (A) and of 2-aminonaphthoquinone with vinyl arenes (B) in the presence of mercury(II) oxide and iodine induced regioselective P-fragmentations of the cyclobutanoxyl radicals to give a 2,3-dihydronaphtho[2,3-h]furan-4,9-dione and its [ l,2-h]furan-4,5-dione isomer (Scheme 76). 

The photochemistry of 2-pentanone follows the pattern of the other small ketones in that photodissociation occurs to form radicals in processes (I), (II), and (III), but an additional photodecomposition pathway appears (Calvert et al., 2008). This is the smallest ketone that exhibits photodecomposition by the Norrish type-II rearrangement in process (IV) that occurs in all aldehydes and ketones that contain a y-hydrogen atom. Also process (V) leading to a cyclobutanol derivative has been observed. 

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