Intermolecular facial diastereoselectivity

The intermolecular [2 + 2]-photocycloaddition of para-tetrahydronaphthoqui-nones has been applied by Ward et al. to the synthesis of cyathin diterpenes [52], An example is represented by the total synthesis of ( )-allocyathin B3 (46), during the course of which the diastereoselective [2 + 2]-photocycloaddition of allene to substrate 44 served as one of the pivotal steps (Scheme 6.17) [53]. The addition delivered a mixture of regioisomers (r.r. = 80/20), from which compound 45 was separated. The facial diastereoselectivity was perfect due to the concave shape of the quinone. 

A non-biomimetic synthesis of /J-(-)-horsfiline (57) has also been recently reported which was based on a thermal intermolecular 1,3-dipolar cycloaddition reaction as outlined in Scheme 7 [63J. The reaction of the optically active menthyl ester 67 acting as a dipolarophile, with the JV-methylazomethine ylide 68 (thermally generated in situ from sarcosine and formaldehyde) proceeded with n-facial diastereoselectivity to produce a chromatographically separable mixture of 69 and the unwanted diastereomer. Subsequent cleavage of the chiral auxiliary, followed by removal of the carboxylic acid group by the Barton radical method provided J7-(-)-horsfiline. 

Bach, T., Bergmann, H., Harms, K., High Facial Diastereoselectivity in the Photocycloaddition of a Chiral Aromatic Aldehyde and an Enamide Induced by Intermolecular Hydrogen Bonding, J. Am. Chem. Soc. 1999,121, 10650 10651. 

Bach, T, Bergmann, H., and Harms, K., High facial diastereoselectivity in the photocycloaddition of a chiral aromatic aldehyde and an enamide induced by intermolecular hydrogen bonding, /. 

Trisubstituted 2-azetidinones have been prepared by diastereoselective and jr-facially selective Lewis acid-catalyzed intermolecular Diels-Alder reactions of 3-butadienylazetidin-... 

The diastereoselectivity inherent to the Diels-Alder reaction can be seen in most of the examples in preceding reactions. The reaction is not, however, enantioselective since there is no facial control for intermolecular reactions (some facial control is available for intramolecular reactions). The ortho rule, the endo rule (secondary orbital interactions), and steric interactions provide some orientational control but facial control is also required for enantioselectivity. When ethyl acrylate reacts with 2-methyl-1,3-pentadiene, it can approach from the bottom as in 247A or from the top as in 247B. Clearly, the two products (248A and 248B) are mirror images and enantiomers. This lack of facial selectivity leads to racemic mixtures in all Diels-Alder cyclizations discussed to this point. 

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