Cyclobutanones, conformation

The cyclobutanone 105, on thermolysis at 190°C, undergoes a retro-ene reaction yielding the crystalline 0,y-unsaturated ketone 115. This product in the solid regenerates 105 photochemically, in almost quantitative yield, whereas in solution the diketone 116 is the exclusive photoproduct. The ketone 115 is found in the solid to have the conformation 115a, a conformation that results, presumably, from the requirement for the bulky methyl at C-7 to adopt the pseudo-equatorial rather than the pseudoaxial position. This molecule in fact has a shape... 

Formation of CK-configurated cyclobutanones has also been observed with 2-methylcyclopen-tanone and 2-methylcyclohexanone/8 However, stereoreversed eyclobutanone formation can be achieved by opening the intermediate oxaspiropentane with sodium phenyl selenide, oxidation of the resulting / -hydroxy selenide with 3-chloroperoxybenzoic acid and subsequent rearrangement in the presence of pyridine/18 Thus, from one oxaspiropentane 8, either stereoisomeric eyclobutanone cis- or lrans-9 was produced. The stereoreversed eyclobutanone formation proceeds from a stereohomogenous / -hydroxy selenoxide and is thought to be conformationally controlled. 

A half-boat conformation of the cyclobutanone ring (in an octant projection) of 74 correctly explains the observed positive CD near 300 nm. A pseudo-axial chlorine substituent in 75 substantially enhances the positive Cotton effect. The cyclobutanone ring in 76 is nearly planar, thus the effect of exo and endo chloro substituents is effectively cancelled while the remainder of cholestane skeleton resides in a negative octant175. 

Eight derivatives of the dihydrodiazocine, for example 1, were prepared utilizing the known reaction of 1,2,4,5-tetraazines with the enolate of cyclobutanones with the aim to obtain the isoxazolyl eight-membered diazahetero-cycles with relatively few low-energy conformationally accessible states and, in turn, limited conformational flexibility <2006JOC2480>. 

Considering the "empirical rules" developed in the previous section, we can develop a simple general hypothesis to help us to understand all the results which conform to these rules direct excitation of cyclobutanones results in the formation of a reactive singlet state which predominantly undergoes a-cleavage to a singlet biradical,... 

The variation of rotational constants with ring-puckering vibrational state is very sensitive to the presence of a barrier at the planar conformation. This is shown for cyclobutanone16 and methylenecyclobutane17) in Fig. 2.6. The presence of a very small barrier, ca. 7.6 cm-1 in the case of cyclobutanone, causes deviation from a smooth variation for the lower levels. In the case of methylenecyclobutane, a very pronounced zig-zag of the rotational constants is observed due to the presence of a 140 cm-1 barrier. The dependence of the rotational constants on vibrational state may be used quantitatively to determine the shape of the potential function as discussed in subsequent sections. 

In both cases, these transformations are regioselective, and each has been used to make natural products with an excellent enantiomeric excess (Figure 9.4). Since both enantiomers of 1.5 (R = Ph) are available, either (K)- or (S)-dichloro-cyclobutanone can be prepared. The favored conformation of the end ether is probably s-trans, and the aromatic substituent hinders one face of the double bond so the reaction with dichloroketene occurs on the other face. End ethers of other chiral alcohols give less useful results [1528],... 

The effect of substituents on the temperature dependence of a-carbonyl-carbene reactivity has been examined using carbenes generated by low-temperature photolysis of methyl diazophenylacetate. A correction to the literature on the photoreaction of isopropylidene diazomalonate (98) with 1,3,3-trimethyl-cyclohexane (99) has been reported. The photoproduct, originally thought to be a cyclopropane derivative, has now been shown to be the cyclobutanone (100), the formation of which presumably involves a photo-Wolff rearrangement as illustrated in Scheme 11. Substituent effects observed in the product distribution of diazo-amide photochemistry have been ascribed to conformational factors the jS-lactam, oxindole, and Wolff rearrangement products appear to arise directly from the excited singlet state of the sym-Z form of the diazo-amide itself. 

In a novel approach, Trost and Keeley (102) used the annelation reagent lithiocyclopropylphenyl sulfide (85) to prepare first cyclobutanone (88) and then the fused biscyclobutane spiro system (89) as a mixture of diastereomers with the desired conformer in fom fold excess (Scheme 16). Haloform-type cleavage afforded cyclobutane derivative (90), which upon transformation of the various functionalities yielded grandisol. 

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