Stereoselectivity cyclobutanols

Another example of a diene undergoing a [2 + 2] cycloaddition reaction with an alkene has been reported recently4. 2-Dimethylaluminumoxy-l,3-cyclohexadiene (7) reacted with phenyl vinyl sulfoxide (8) to afford a diastereomeric mixture of cis substituted cyclobutanols 9 (equation 3). The occurrence of a [2 + 2] cycloaddition as well as the high cis stereoselectivity observed were explained by a pre-organization of the reactants by complexation of the diene bound aluminum with the sulfoxide oxygen on the olefin. 

Griesbeck, A.G. and Heckroth, H. (2002) Stereoselective synthesis of 2-amino-cyclobutanols via photocyclization of... 

There has been considerable interest in the factors that control the stereoselectivity of cyclobutanol formation. Three main factors were identified quite early pre-existing conformational preferences due to steric effects or to internal hydrogen bonding solvation of the OH group and variable rotational barriers for cyclization. More recently Griesbeck has proposed that orbital orientation favoring soc produces another form of conformational preference in triplet biradicals [55], These factors have different importance depending upon the molecule. 

An intriguing combination of two cyclopropyl systems allows cyclobutanone formation according to equation 105 base-induced fragmentation of an intermediate cyclobutanol stereoselectively forms a functionalized olefin . 

O-Pivaloyl-D-galactopyranosides were shown to be efficient stereodifferentiating tools [9]. Thus, the [2-1-2] cycloaddition of dichloroketene to chiral vinyl galactoside 27 afforded the cyclobutanone 28 with reasonable stereoselectivity (dr 4 1) [26] (Scheme 10.6). The resulting 2,2-dichlorocyclobutanones are reactive and often cannot be isolated in pure form. More stable cyclobutanols were isolated after reduction of the keto group [26]. 

This procedure is an adaptation of a photoannulation reaction, originally developed by de Mayo ( ref 22 ) and leads initially to the stereoselective formation of a cyclobutanol ring (intermediate 44 ) which undergoes a spontaneous ring opening to the typical iridoidic dialdehyde ( intermediate 45 ) which is theoretically in equilibrium with the lactol iridoidic moiety ( intermediate 46 ), as depicted in the scheme 9. 

This constitutes the first catalytic enantioselective vinylogous a-ketol rearrangement reported in the literature. As depicted in Scheme 10.7, the reaction affords the corresponding spirocyclic rings in good yields and excellent stereoselectivities. The scope of the reaction is rather limited because of the nature of the vinylogous a-ketol rearrangement, which requires the presence of cyclobutanol moieties. 

Studies of solvent and multiplicity effects on the efficiency and stereochemistry of cyclobutanol formation from 1-adamantylacetone are reported. Quantum-yield measurements indicate that efficiency is about three times greater in methanol than in benzene. The cyclobutanol product ratio (339) (340) is 1,0—1.8 1 from Ty of the ketone and ca. 5 1 for the excited singlet state reaction. The stereoselectivity of the excited singlet state reaction accords with the picture in which the short-lived 1,4-biradical undergoes rehybridization with preferential rotation and closure, for steric reasons, to yield (339) rather than (340). 

Rh-catalyzed stereoselective isomerization of tert-cyclobutanols into chiral indanoles 2.2.1 Overview... 

Figure 2.6 Computed catalytic cycle for Rh-Catalyzed Stereoselective Isomerizatioit of fert-Cyclobutanol tcb imder DFT/B3LYP/LANL2DZ(Rh)/6-31G (all other) level of fheoiy in the gas-phase. (Data from Yu, H. et al., Chem. Fur.., 20,3839-3848,2014.)...

A distinction is often made between coiled and stretched conformations in order to rationalize cyclization/ cleavage ratios however, disproportionation also requires a coiled conformation, and it is not at all clear what affects the competition between cyclization and disproportionation, other than that hydrogen bonding to Lewis bases dramatically inhibits the latter and changes the stereoselectivity of the former. The bond rotations needed to initiate both cyclization and disproportionation must be different, but they likely are quite small and thus not very different. Examples of the wide variations among cyclization/ disproportionation ratios are provided in Table 58.2. Inasmuch as conformer populations determine product ratios, cyclobutanol yields are determined primarily by how weU cycHzation competes with disproportionation. 

Table 58.2 also indicates diastereomer ratios for the cyclobutanols formed from some of the ketones. One particularly interesting case involves a-methylbutyrophenone (aMeBP) and valerophenone (VP) forming the same 2-methyl-1-phenylcyclobutanol but with much different stereoselectivity. aMeBP forms a single isomer with the methyl and phenyl groups trans, whereas VP forms a 3 1 ratio favoring that isomer. VP exemplifies stereoselectivity induced by nonbonded interactions created as the two radical sites approach each other, whereas aMeBP exemplifies stereoselectivity induced by pre-existing nonbonded interactions in the biradical. In the former case, selectivity appears to mirror relative product energies in the latter, it mirrors relative biradical conformational preferences. Scheme 6 illustrates both types of selectivity. 

A much bigger symmetric macrocycle, crystalline 1,14-cyclohexacosanedione exists as both plates and needles. When irradiated as crystals, the former yields only a cis-cyclobutanol, while the latter form gives the trans-cyclobutanol with >90% selectivity neither undergoes type II elimination. In solution, type II cleavage accounts for half the products, the other half are cyclobutanols in a 2.3 1 trans/ds ratio. These results provide another example of how crystal lattices enforce conformationally driven stereoselectivity, which can vary with the exact crystal morphology. A full paper has been published that provides details for a wide range of symmetric and unsymmetric cycloalkanediones. ... 

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