Allylic vinylepoxides

Metzner and co-workers reported a one-pot epoxidation reaction in which a chiral sulfide, an allyl halide, and an aromatic aldehyde were allowed to react to give a trons-vinylepoxide (Scheme 9.16c) [77]. This is an efficient approach, as the sulfonium salt is formed in situ and deprotonated to afford the corresponding ylide, and then reacts with the aldehyde. The sulfide was still required in stoichiometric amounts, however, as the catalytic process was too slow for synthetic purposes. The yields were good and the transxis ratios were high when Ri H, but the enantioselectivities were lower than with the sulfur ylides discussed above. 

The outcomes of intramolecular cyclizations of hydroxy vinylepoxides in more complicated systems can be difficult to predict. In a study of the synthesis of the JKLM ring fragment of dguatoxin, epoxide 44 was prepared and subjected to acid-mediated cydization conditions (Scheme 9.24) [114]. Somewhat surprisingly, the expected oxepane 45 was not formed, but instead a mixture of tetrahydropyran 46 and tetrahydrofuran 47 was obtained, both compounds products of attack of the C6 and C5 benzyl ether oxygens, respectively, on the allylic oxirane position (C3). Repetition of the reaction with dimsylpotassium gave a low yield of the desired 45 along with considerable amounts of tetrahydropyran 48. 

Addition of carbon nucleophiles to vinylepoxides is of particular importance, since a new carbon-carbon bond is formed. It is of considerable tactical value that conditions allowing for regiocontrolled opening of vinyloxiranes with this type of nucleophiles have been developed. Reactions that proceed through fonnation of a rr-allyl metal intermediate with subsequent external delivery of the nucleophile, or that make use of a soft carbon nucleophile, generally deliver the SN2 product. In contrast, the Sn2 variant is often the major reaction pathway when hard nucleophiles are employed. In some methods a nucleophile can be delivered selectively at either the Sn2 or SN2 positions by changing the reaction conditions. 

Additions of carbon nucleophiles to vinylepoxides are well documented and can be accomplished by several different techniques. Palladium-catalyzed allylic alkylation of these substrates with soft carbon nucleophiles (pKa 10-20) proceeds under neutral conditions and with excellent regioselectivities [103, 104]. The sul-fone 51, for example, was cyclized through the use of catalytic amounts of Pd(PPh3)4 and bis(diphenylphosphino)ethane (dppe) under high-dilution conditions to give macrocycle 52, an intermediate in a total synthesis of the antitumor agent roseophilin, in excellent yield (Scheme 9.26) [115, 116]. 

Pd(0)-catalyzed hydrogenolysis of vinylepoxides offers an attractive regio- and dia-stereoselective route to homoallylic alcohols (Scheme 9.36) [104, 155, 156]. Thus, hydrogenolysis of ( ) olefin 88 affords syn isomer 89 with inversion of configuration at the allylic carbon, while subjection of (Z) isomer 90 to identical reaction conditions results in the anti isomer 91. The outcomes of these reactions are ex-... 

Chiral racemic vinylepoxides react with phthalimide at the more substituted end of the 7t-allyl intermediate to give the chiral allylamine in up to 98% ee. Scheme 34 [ 116]. Some modification of the standard DPPBA-type ligand was required in order to achieve this level of selectivity. In particular, increased steric bulk in the form of a naphthyl moiety was claimed to restrict the number of ro-tamers and thereby increase the selectivity. This sequence was used to prepare vinylglycinol and a related reaction was used to synthesize a key intermediate for the synthesis of some anti-fungal agents [117]. 

Vinylepoxides (e.g., 61) undergo TsOH-catalyzed aminolysis regioselectively at the allylic position to give vicinal amino alcohols (e.g., 62) in generally high yields, although the reaction is sensitive to steric bulk about the epoxide nucleus <97TL2027>. 

One method to prepare cyclic carbonates of the structural type shown in Scheme 44 is by direct reaction of 1,2-diols with a phosgene synthetic equivalent, but they can also be prepared by Pd(0)-catalyzed reaction of vinylepoxides with carbon dioxide. Trost and Granja have found that the behavior of vinylepoxides and their related carbonates in Pd(0)-catalyzed allylations is different from the stereochemical viewpoint. ... 

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