“…Under optimal conditions, we were able to show that the process could be applied to a range of aromatic, 20 aliphatic, and base-sensitive aldehydes. 21 Having developed a catalytic process with good substrate scope, the next goal was to make it asymmetric.…”
Section: Introduction To Sulfur Ylide-mediated Epoxidationmentioning
The reaction of sulfur ylides with carbonyl compounds to give epoxides is an important synthetic method. This Account charts the recent advances in rendering this process both asymmetric and catalytic. Two catalytic methods have been developed: the first involving the reaction of a sulfide with an alkyl halide in the presence of a base and aldehyde and the second involving the reaction of a sulfide with a diazo compound or diazo precursor in the presence of a metal catalyst and aldehyde. These catalytic methods coupled with suitable chiral sulfides provide a new catalytic asymmetric epoxidation process for the preparation of epoxides. The scope of the two catalytic processes is discussed together with the factors that influence both relative and absolute stereochemistry. The application of these methods in target-orientated synthesis is also reviewed.
“…Under optimal conditions, we were able to show that the process could be applied to a range of aromatic, 20 aliphatic, and base-sensitive aldehydes. 21 Having developed a catalytic process with good substrate scope, the next goal was to make it asymmetric.…”
Section: Introduction To Sulfur Ylide-mediated Epoxidationmentioning
The reaction of sulfur ylides with carbonyl compounds to give epoxides is an important synthetic method. This Account charts the recent advances in rendering this process both asymmetric and catalytic. Two catalytic methods have been developed: the first involving the reaction of a sulfide with an alkyl halide in the presence of a base and aldehyde and the second involving the reaction of a sulfide with a diazo compound or diazo precursor in the presence of a metal catalyst and aldehyde. These catalytic methods coupled with suitable chiral sulfides provide a new catalytic asymmetric epoxidation process for the preparation of epoxides. The scope of the two catalytic processes is discussed together with the factors that influence both relative and absolute stereochemistry. The application of these methods in target-orientated synthesis is also reviewed.
“…An alternative method for ylide formation involves the reaction of a sulfide with a carbene or metal carbenoid. , Indeed, we recently reported the successful application of this strategy to carbonyl epoxidation using catalytic quantities of sulfide (Scheme ) . As these reaction conditions do not require the use of strong base, this method can be applied to readily enolizable and even base-sensitive aldehydes. , In this paper we describe the design and optimization of chiral sulfides for use in the catalytic cycle (Scheme ) to produce nonracemic epoxides and our studies into the mechanism of the enantioselectivity. 4 …”
A range of 1,3-oxathianes based on camphorsulfonic acid have been prepared and tested in the
catalytic asymmetric epoxidation of carbonyl compounds. It was found that the 1,3-oxathiane derived from
acetaldehyde 5b gave the highest yield and enantioselectivity in the epoxidation process. The enantioselectivity
was independent of the solvent and metal catalyst used (although yields were dependent on both). The optimum
conditions were applied to a range of aldehydes, and good enantioselectivities and diastereoselectivities were
observed. The origin of the enantioselectivity was probed, and in particular the role of the oxygen of the
1,3-oxathiane was investigated. Thus, the sulfur and carbon analogues of the camphorsulfonic acid based
1,3-oxathiane (derived from formaldehyde) were prepared (i.e., 1,3-dithiane and thiane analogues). With this
series of analogues the steric effects are minimized so that the electronic effects can be investigated. The
series of compounds was reacted in the catalytic cycle with benzaldehyde and gave stilbene oxides with 44%
ee (sulfur analogue), 41% ee (1,3-oxathiane), and 20% ee (carbon analogue). Thus, it was concluded that the
oxygen of the 1,3-oxathiane exerted a significant electronic effect in controlling the face selectivity of the
ylide reactions. This electronic effect was a result of combined anomeric (higher with the sulfur analogue,
not present with the carbon analogue) and Cieplak effects. A strong anomeric effect was observed in the
X-ray structures of one of the 1,3-oxathianes, and an even greater one was observed in the corresponding
sulfoxide (this was used as an electronic analogue of the ylide). The face selectivity of the ylide was believed
to be complete in reactions with 5b. The minor enantiomer resulted from reaction of the minor conformer of
the ylide, reacting again with high face selectivity. This was proven by using a more substituted diazo compound,
which was expected to give much less of the minor conformer. Indeed, reaction with mesityldiazomethane
gave the corresponding epoxide in essentially enantiomerically pure form.
“…In yet another approach, Tanzawa and co-workers reported the generation of S -benzylsulfonium ylides via fluoride-mediated desilylation of trimethylsilylmethylbenzyl sulfonium precursors under essentially nonbasic conditions . The generation of sulfur ylides under mild conditions has been shown to be particularly beneficial in situations where base-sensitive aldehydes are employed …”
A novel protocol for the generation of sulfur ylides is described. The overall process involves thermal decarboxylation of a carboxymethylsulfonium betaine to give a sulfur ylide that, in the presence of an aldehyde, affords the corresponding terminal oxirane. Yields were found to correlate with the electron deficiency of the aryl aldehyde. In situ generation of betaine in the presence of an aldehyde successfully afforded the desired oxirane in moderate yield, thus demonstrating the feasibility of a catalytic process. [reaction: see text]
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
