Stereochemistry of cycloaddition

Another strategy to control the regio- and stereochemistry of cycloaddition is a silicon-tethered reaction, as discussed in the section of nitronates (Section 8.2.3) (Eq. 8.65).100... 

A directing effect of a methyl group at the allylic stereocenter, located between the nitrile oxide and the alkene moieties, on the stereochemistry of cycloaddition was found with the carbon analogues (Scheme 6.46 and Table 6.14) (18,256). 

Stereochemical path of 1,3-dipolar cycloadditions as shown above. As the major secondary orbital interaction works on the substituents of dipoles, the stereochemistry of cycloadditions depends upon the ylide configuration. A more reliable methodology to control the stereochemistry of cycloadditions has been recently developed. In the cycloadditions of N-metallated azomethine ylides with carbonyl-activated olefins, the carbonyl oxygyen chelates the metal to allow the endo approach of olefinic dipolarophiles. 

The stereochemistry of cycloaddition of chiral alkyl ketenes with imines has been explored in cycloadditions designed to prepare intermediates for carbapcncm synthesis. Reaction of kctcnc (S)-57, prepared by treatment of the acid chloride with diisopropylethylamine at —40 C. with imine 58 gives 90% of the cw-/3-lactam 59 with d.r. [(35,47 )/(3/f,45 )] 87.5 12.579. The ketene rat-60 reacts with imine 61 to give the ci x-/3-lactam 62, d.r. [(2R, 3R )I(2S, 3S )] 70 30 80. 

A firm mechanistic understanding of concerted cycloadditions had to await the formulation of the reaction mechanism within the framework of molecular orbital theory. Consideration of the molecular orbitals of reactants and products revealed that in some cases a smooth transformation of orbitals of the reactant to those of the product is possible. In other cases, reactions that appear feasible, if no consideration is given to the symmetry and spatial orientation of the orbitals, are found to require high-energy transition states when the orbital properties are considered in detail. Those considerations have permitted description of many types of cycloadditions as allowed or forbidden. As has been discussed (Part A, Chapter 10), the application of orbital-symmetry relationships permits a conclusion as to whether a given concerted reaction is or is not energetically feasible. In this chapter, the synthetic application of these reactions will be emphasized. The same orbital-symmetry relationships that are informative as to the feasibility of a given reaction often are predictive of features of the stereochemistry of cycloaddition products. This predictable stereochemistry is an attractive feature for synthetic purposes. 

Cyclohexenes and Cyclohexadienes. The stereochemistry of cycloadditions to methyl-enecyclohexanes has been a somewhat neglected area. Recently, the addition of dichloroketen and chlorosulphonyl isocyanate to methylenecyclohexane and 4-t-butylmethylenecyclohexane has been studied as models for a 2s + 2a allowed cycloaddition. The reaction is kinetically controlled and axial attack dominates, yielding the thermodynamically less stable isomer (as confirmed by a molecular mechanics calculation). There is complete regiospecificity due to the polar character of the transition state. 

The stereochemistry of cycloaddition of phenyl azide to hexamethyl Dewar benzene has been established by an X-ray diffraction structural analysis of the cjco-isomer of a )z-bromo-derivative of triazoline (240). The exo-triazoline thus formed was converted into the ejro-aziridine (241) by u.v. light. The addition of cyanogen azide to hydrocarbon olefins yields 1-... 

Electrocycllc Reactions Cycloadditlon Reactions Stereochemistry of Cycloadditions... 

CYCLOADDITION REACTIONS Stereochemistry of Cycloaddition Reactions Molecular Orbitals in Cycloaddition Reactions... 

---