Direct Asymmetric Epoxidation of Aldehydes Using Catalytic Amounts of Enantiomerically Pure Sulfides

Aggarwal, Varinder K.; Ford, J. Gair; Thompson, A.; Jones, Ray V. H.; Standen, M. C.

doi:10.1021/ja961144+

Cited by 131 publications

(60 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As expected, the control compound 12 yielded the product with the same absolute con®guration but with low enantioselectivity, underlining the crucial role of the gem-dimethyl function. The absolute stereochemistry of the product is consistent with the previously proposed reaction mechanism 3,5 and the stereochemistry of 11. The yield observed in the epoxidation with 11 as a catalyst was low (16%) but is well in line with the structurally corresponding catalyst 14 (11%) 2b , ( Table 1).…”

Section: ±20supporting

confidence: 88%

“…3 As the primary focus of our molecular design efforts is stereoselectivity, the literature conditions 3 were mimicked as closely as possible so that the stereoselectivity of 11 could be directly compared to those of reported catalysts.…”

Section: ±20mentioning

confidence: 99%

“…Furthermore, the recently introduced carbene-based conditions allow the use of catalytic amounts of sul®des and have expanded the scope of the reactions to base-sensitive substrates, such as enolizable aldehydes. 3 As different applications are likely to have different optimal chiral sul®des, easy ®ne tuning is a highly desirable property. Here, we describe the computer-assisted design of a novel family of chiral sul®des 2 that (1) offers a high degree of variability, (2) can be synthesized using a general route from common starting materials 1 and (3) is accessible in both enantiomeric forms (Scheme 1).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Computer-assisted discovery of novel amino acid derived sulfides for enantioselective epoxidation of aldehydes

Myllymäki

Lindvall²,

Koskinen³

2001

Tetrahedron

View full text Add to dashboard Cite

Section: ±20supporting

confidence: 88%

Section: ±20mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Computer-assisted discovery of novel amino acid derived sulfides for enantioselective epoxidation of aldehydes

Myllymäki

Lindvall²,

Koskinen³

2001

Tetrahedron

View full text Add to dashboard Cite

“…Although sulfur ylide reactions have traditionally operated with stoichiometric amounts of sulfonium salts, we have recently reported a user-friendly, catalytic, and asymmetric process for epoxidation of carbonyl compounds that operated under neutral conditions by using tosylhydrazone sodium salts as diazocompound precursors and substoichiometric amounts (5 mol% in many cases) of chiral sulfide 1 and metal catalyst (Scheme 1) (13)(14)(15)(16). This chiral sulfide could be recovered in high yield and reused without any loss of asymmetric induction.…”

mentioning

confidence: 99%

Effect of sulfide structure on enantioselectivity in catalytic asymmetric epoxidation of aldehydes: Mechanistic insights and implications

Aggarwal

Charmant

Dudin

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Bridged bicyclic sulfide 1 was originally found to provide high levels of asymmetric induction in sulfur ylide-mediated epoxidations. This sulfide possesses chirality in the [2.2.1] thioether moiety and the [2.2.1] camphor-derived carbocyclic moiety. To determine whether the optimal sulfide had been used, a diastereomer of sulfide 1 in which the stereochemistry of the [2.2.1] carbocycle was reversed (sulfide 5) was prepared and studied as an epoxidation catalyst. This diastereomer gave considerably lower levels of asymmetric induction than the original sulfide 1. From computational and x-ray studies it was found that sulfide 5 gave rise to a more hindered ylide, which reacted more reversibly with aldehydes leading to lower enantioselectivity. Conditions that reduced reversibility were also tested and high enantioselectivities were returned for sulfide 5 (similar to sulfide 1). The implications for the synthesis of chiral sulfides for asymmetric epoxidations are discussed.T he reaction of sulfur ylides with carbonyl compounds to give epoxides (1-8) provides a complementary method with oxidation of alkenes (9-12) for the preparation of these valuable synthetic intermediates. Although sulfur ylide reactions have traditionally operated with stoichiometric amounts of sulfonium salts, we have recently reported a user-friendly, catalytic, and asymmetric process for epoxidation of carbonyl compounds that operated under neutral conditions by using tosylhydrazone sodium salts as diazocompound precursors and substoichiometric amounts (5 mol% in many cases) of chiral sulfide 1 and metal catalyst (Scheme 1) (13-16). This chiral sulfide could be recovered in high yield and reused without any loss of asymmetric induction. A broad range of aldehydes, including aromatic, aliphatic, and certain ␣,␤-unsaturated aldehydes, could be converted into the corresponding epoxides in generally high yield with high levels of enantioselectivity and diastereoselectivity (17). Sulfide 1 could also be used in a stoichiometric variant of this process, which allows access to epoxides that are difficult to form using the catalytic protocol (18).We have recently proposed a model to explain the high enantioselectivity in this system based on both experimental and computational data (Scheme 2) (19). The high enantioselectivity observed resulted from ylide 2A being strongly favored over 2B because of steric interactions between the ylide substituent and methylene unit of the [2.2.1] bicycle, and the high face selectivity in reaction of ylide conformer 2A was due to the camphor moiety effectively blocking attack from the si face. Based on this model, the camphor moiety was simply acting as a sterically large blocking group. But was it? If that was simply its role, similar levels of enantioselectivity should result from the diastereomer 5 where the carbonyl group is placed on the right of the [2.2.1] carbocycle (Fig. 1). ‡ In contrast, if the current model is too simplistic and the carbonyl group of the camphor skeleton does play a subtle role in contro...

show abstract

“…Scheme 7 Another chiral, sulfide-catalyzed asymmetric ylide aziridination also appeared in 1996 [17], which gave high ee values and proceeded in a catalytic mode, albeit it requires strict reaction conditions and suffers from low trans/cis selectivity (Ϸ3/1). The present asymmetric aziridination is a stoichiometric reaction but may represent a promising general and practical approach to optically active aziridines due to its compatibility with a wide range of substrates, high yields, and very mild reactions conditions.…”

Section: Aziridination Via Ylide Routementioning

confidence: 99%

Stereoselective synthesis of three-membered ring compounds via ylide routes

Dai¹,

Hou²,

Zhou³

1999

Pure and Applied Chemistry

View full text Add to dashboard Cite

Three types of small ring compounds (epoxides, aziridines and cyclopropanes) can be synthesized stereoselectively via ylide route. Among them, the stereochemistry of vinyloxiranes, vinylaziridines, cyclopropylesters, amides and ketones can be tuned by the choice of reaction conditions and ylides with varying heteroatoms and ligands. Optically active epoxides and acetylenylaziridines can be prepared via camphor-derived chiral sulfonium ylide routes.

show abstract

Direct Asymmetric Epoxidation of Aldehydes Using Catalytic Amounts of Enantiomerically Pure Sulfides

Cited by 131 publications

References 25 publications

Computer-assisted discovery of novel amino acid derived sulfides for enantioselective epoxidation of aldehydes

Computer-assisted discovery of novel amino acid derived sulfides for enantioselective epoxidation of aldehydes

Effect of sulfide structure on enantioselectivity in catalytic asymmetric epoxidation of aldehydes: Mechanistic insights and implications

Stereoselective synthesis of three-membered ring compounds via ylide routes

Contact Info

Product

Resources

About