Stereoselective Synthesis of 2-Deoxy-β-Galactosides via 2-Deoxy-2-bromo- and 2-Deoxy-2-iodo-galactopyranosyl Donors

Durham, Timothy B.; Roush, William

doi:10.1021/ol034393t

Cited by 54 publications

(26 citation statements)

References 31 publications

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“…[12] Although mechanisms involving bridged intermediates such as the episulfonium ions 4 and 8 provide concise and satisfying explanations for observations such as those shown in Schemes 1 and 2, accumulating evidence suggests that such intermediates may not be involved in stereoselective substitution processes. The fact that reactions that would be expected to proceed through episulfonium, [6,7,[13][14][15] episelenonium, [13,16] or iodonium ions [9,10] (9, Figure 1) are not completely selective [17] indicates that these reactions may occur by a different pathway or through multiple pathways. The formation of the product that would not correspond to stereospecific opening of the onium ion 9 (i.e., the 1,2-cis product) is typically explained by invoking oxocarbenium ions 10 as reactive intermediates.…”

Section: Introductionmentioning

confidence: 99%

Nucleophilic Substitution Reactions of 2‐Phenylthio‐Substituted Carbohydrate Acetals and Related Systems: Episulfonium Ions vs. Oxocarbenium Ions as Reactive Intermediates

2008

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A powerful approach for controlling the stereochemistry of glycosylation reactions involves using a directing group at an adjacent carbon to influence the stereochemistry of nucleophilic attack. The use of substituents such as I, PhS, and PhSe has proven to be especially valuable because it enables the preparation of 2‐deoxysugars after reductive removal of the directing group. The mechanisms of these reactions are generally considered to involve nucleophilic opening of bridged onium ions and to proceed with inversion. Onium ions, however, equilibrate with open cations, and these open forms can be favored when the cation is highly stabilized. Although the selectivities of reactions of carbohydrate‐derived cations are consistent with the intermediacy of onium ions, the reactions of acyclic cations are not. Instead, consideration of the preferred conformations of the oxocarbenium ions and stereoelectronically favored additions to these intermediates provides a predictive model to explain the diastereoselectivities observed in reactions of oxocarbenium ions bearing proximal heteroatoms.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

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Section: Introductionmentioning

confidence: 99%

Nucleophilic Substitution Reactions of 2‐Phenylthio‐Substituted Carbohydrate Acetals and Related Systems: Episulfonium Ions vs. Oxocarbenium Ions as Reactive Intermediates

2008

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“…[7] Using directing groups at C-2 that are later removed is inherently inefficient. [6,8] Many direct methods rely on stoichiometric promoters and/or precursors that require several steps to synthesize. [9] Catalyzing the direct addition of an alcohol to a glycal (2) is the most atom-efficient route to 2-deoxyglycosides.…”

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confidence: 99%

“…To that end, perbenzylated galactal 2 d was used as a model donor and reacted with a range of differentially protected glycosyl acceptors 3 b-3 j under the optimized reaction conditions. Glycosyl acceptors with a primary alcohol [20] and either benzyl or benzoyl protecting groups, as well as either methoxy or thiophenyl as the anomeric substituents gave yields of the isolated product of 87-98 % and a-selectivity (Table 2, entries 1, 2, 8,9).…”

mentioning

confidence: 99%

α‐Selective Organocatalytic Synthesis of 2‐Deoxygalactosides

Balmond

Coe

Galan³

et al. 2012

Angew Chem Int Ed

155

139

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“…Highly selective methods for the synthesis of 2-deoxy-␤-glycosides by using 2-iodo-glycosyl acetate, trichloroacetimidate, and fluoride donors were recently reported from this laboratory (49)(50)(51)(52)(53). These glycosidation reactions afford the ␤-glycosides in high yield and with excellent ␤-selectivity.…”

Section: Synthesis Of Glycosyl Donor 30mentioning

confidence: 99%

Total synthesis of (–)-spinosyn A

Mergott

Frank

Roush

2004

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

Self Cite

125

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A convergent, highly stereoselective total synthesis of (؊)-spinosyn A (1) is described. Key features of the synthesis include the transannular Diels-Alder reaction of macrocyclic pentaene 11 and the transannular Morita-Baylis-Hillman cyclization of 12 that generates tetracycle 26. The total synthesis of (؊)-spinosyn A was completed by a sequence involving the highly ␤-selective glycosidation reaction of 13 and glycosyl imidate 30.T he spinosyns are a family of polyketide natural products that possess extraordinary insecticidal activity. The biosynthetic mixture, generated by Saccharopolyspora spinosa, comprises mostly spinosyn A (1) (Scheme 1) (Ϸ85%) and spinosyn D (Ϸ10-15%) (1-8). This mixture is currently marketed for use as an insecticide against a variety of insects (6). Total syntheses of spinosyn A have been reported by Evans and Black (9) and Paquette et al. (10,11). Synthetic StrategyDiels-Alder reactions have been proposed as key steps in the biogenesis of several natural products, including lovastatin, solanapyrone, nargenicin, and ikarugamycin (12). Kirst et al. (3) suggested that the biosynthesis of spinosyn A may involve a transannular Diels-Alder (TDA) (13) reaction of a macrocyclic pentaene to form the C(4)OC(12) and C(7)OC (11) bonds (see 4 3 3; Scheme 1). Kirst also suggested that a transannular cyclization of a 1,3-dicarbonyl nucleophile may generate the C(3)OC (14) bond (3). Alternatively, we speculated that the C(3)OC(14) bond may be formed by a vinylogous Morita-Baylis-Hillman (MBH) reaction mediated by an enzymatic nucleophile (compare 3 3 1; Scheme 1). Based on these biosynthetic considerations, we sought to assemble spinosyn A (1) via a TDA and MBH cyclization sequence of an appropriately functionalized macrocyclic pentaene 4.Diastereoselectivity of the Diels-Alder Reaction. Paramount to the success of this synthetic strategy is the control of the diastereoselectivity of the TDA reaction (4 3 3). It is known from the work of Evans and Black (9) that the intrinsic diastereofacial selectivity of the intramolecular Diels-Alder (IMDA) reaction of 5a favors the incorrect C(7)OC(11) trans-fused diastereomer 6a with 6:1 selectivity (Scheme 2). Although Evans and Black (9) addressed this issue by incorporating a chiral auxiliary (13) in the dienophile (see 5b 3 7b), we would not have recourse to this strategy for the TDA cyclization of 4. Thus, some means for controlling the stereochemistry at the C(7)OC(11) ring fusion relative to the C(9)Oalkoxy substituent in the Diels-Alder reaction was required.We initially hoped to use the steric directing-group strategy to control the diastereoselectivity of the Diels-Alder reaction (15-17), which could involve appending a bromine steric directing group at C(6) of the IMDA or TDA substrate to control the stereochemical outcome of the cycloaddition, leading to the desired C(7)OC(11) trans-fused diastereomer. It was anticipated that TS2, which leads to the undesired C(7)OC(11) trans-fused isomer 10 and is favored in the absence of the C(6)OBr steric direct...

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Stereoselective Synthesis of 2-Deoxy-β-Galactosides via 2-Deoxy-2-bromo- and 2-Deoxy-2-iodo-galactopyranosyl Donors

Cited by 54 publications

References 31 publications

Nucleophilic Substitution Reactions of 2‐Phenylthio‐Substituted Carbohydrate Acetals and Related Systems: Episulfonium Ions vs. Oxocarbenium Ions as Reactive Intermediates

Nucleophilic Substitution Reactions of 2‐Phenylthio‐Substituted Carbohydrate Acetals and Related Systems: Episulfonium Ions vs. Oxocarbenium Ions as Reactive Intermediates

α‐Selective Organocatalytic Synthesis of 2‐Deoxygalactosides

Total synthesis of (–)-spinosyn A

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