Neighboring‐Group Participation by C‐2 Acyloxy Groups: Influence of the Nucleophile and Acyl Group on the Stereochemical Outcome of Acetal Substitution Reactions

Chun, Yu Sung; Remmerswaal, Wouter A.; Codée, Jeroen D. C.; Woerpel, K. A.

doi:10.1002/chem.202301894

Cited by 5 publications

(3 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The relative stability of the cations was assessed through a density functional theory (DFT) protocol, in which the conformational energy landscape (CEL) maps for these cations were generated. ,− This method maps the energy of the glycosyl cations as a function of their shape by probing the complete conformational space that these cations can occupy. We plotted the relative stability of the dioxanium ion versus the oxocarbenium ion for the glucosyl (Figure a) and the mannosyl (Figure b) cations.…”

Section: Resultsmentioning

confidence: 99%

Anomeric Triflates versus Dioxanium Ions: Different Product-Forming Intermediates from 3-Acyl Benzylidene Mannosyl and Glucosyl Donors

Remmerswaal,

Elferink,

Houthuijs

et al. 2024

J. Org. Chem.

Self Cite

View full text Add to dashboard Cite

Minimal structural differences in the structure of glycosyl donors can have a tremendous impact on their reactivity and the stereochemical outcome of their glycosylation reactions. Here, we used a combination of systematic glycosylation reactions, the characterization of potential reactive intermediates, and indepth computational studies to study the disparate behavior of glycosylation systems involving benzylidene glucosyl and mannosyl donors. While these systems have been studied extensively, no satisfactory explanations are available for the differences observed between the 3-O-benzyl/benzoyl mannose and glucose donor systems. The potential energy surfaces of the different reaction pathways available for these donors provide an explanation for the contrasting behavior of seemingly very similar systems. Evidence has been provided for the intermediacy of benzylidene mannosyl 1,3-dioxanium ions, while the formation of the analogous 1,3glucosyl dioxanium ions is thwarted by a prohibitively strong flagpole interaction of the C-2-O-benzyl group with the C-5 proton in moving toward the transition state, in which the glucose ring adopts a B 2,5 -conformation. This study provides an explanation for the intermediacy of 1,3-dioxanium ions in the mannosyl system and an answer to why these do not form from analogous glucosyl donors.

show abstract

Section: Resultsmentioning

confidence: 99%

Anomeric Triflates versus Dioxanium Ions: Different Product-Forming Intermediates from 3-Acyl Benzylidene Mannosyl and Glucosyl Donors

Remmerswaal,

Elferink,

Houthuijs

et al. 2024

J. Org. Chem.

Self Cite

View full text Add to dashboard Cite

show abstract

“…The analysis of these reactions emerged during stimulating conversations with the group of Professor Codée. 105 Taken together, we concluded that, just as for the systems with remote substituents (Scheme 45 and Figure 21 ), the presence of an intermediate is not sufficient to say that it is responsible for the stereochemistry of the reaction.…”

Section: Neighboring-group Participation Is Not As Simple As It Seemsmentioning

confidence: 85%

“…Acyloxy groups can engage in participation, but this participation, like in the case of the sulfur system, depended upon the nature of the nucleophile. 105 With relatively weak alkene nucleophiles, the reaction favored the 1,2- cis product (e.g., 246 in Scheme 49 ), but the expected 1,2- trans product became the major product as the nucleophile became more reactive and more hindered (Scheme 49 ). The correlation between reactivity and stereoselectivity was also observed with oxygen nucleophiles (Scheme 50 ).…”

Section: Neighboring-group Participation Is Not As Simple As It Seemsmentioning

confidence: 99%

Acetal Substitution Reactions: Stereoelectronic Effects, Conformational Analysis, Reactivity vs Selectivity, and Neighboring-Group Participation

Woerpel,

Chun,

Luu

2024

Synlett

Self Cite

View full text Add to dashboard Cite

Acetal substitution reactions can proceed by a number of mechanisms, but oxocarbenium ion intermediates are involved in many of these reactions. Our research has focused on understanding the conformational preferences, structures, and reactions of these intermediates. This account summarizes our observations that electrostatic effects play a significant role in defining the preferred conformations, and that torsional effects determine how those intermediates react. Neighboring-group effects are not as straightforward as they might seem, considering that oxocarbenium ion intermediates are in equilibrium with structures that involve stabilization by a nearby substituent.1 Introduction2 Unexpected Stereoselectivities3 Determining Conformational Preferences of Oxocarbenium Ions4 Structures of Carbocations by NMR Spectroscopy and X-ray Crystallography5 Stereoelectronic Models for Reactions Involving Other Oxocarbenium Ions6 Stereoselectivity and Reactivity: When They Correlate, When They Do Not7 Neighboring–Group Participation Is Not as Simple as It Seems8 What Is True for Carbocations Is True for Carbonyl Compounds9 Stereoelectronic and Torsional Effects in Reactions of Enolates10 Summary of Expected Selectivities for Reactions of Cyclic Acetals11 Conclusion

show abstract

The influence of acceptor acidity on hydrogen bond mediated aglycone delivery (HAD) through the picoloyl protecting group

Remmerswaal,

Hoogers,

Hoopman

et al. 2024

Eur J Org Chem

Self Cite

View full text Add to dashboard Cite

The outcome of glycosylation reactions heavily relies on the specific protecting group patterns employed on both the donor and acceptor molecules. The picoloyl (Pico) protecting group stands out as it can steer the stereoselectivity in a glycosylation reaction through hydrogen bond‐mediated aglycone delivery (HAD). This provides syn‐stereoselectivity, with respect to the stereochemistry of the Pico group, by forming a hydrogen bond between the incoming acceptor and the picoloyl ring nitrogen. We here probe how acceptor acidity influences the stereodirecting effect of the picoloyl protecting group. A set of 3‐O‐functionalized glucosyl and mannosyl donors, each bearing different protecting groups (picolinate, nicotinate, isonicotinate, and benzoate), were synthesized for systematic evaluation. For the 3‐O‐picoloyl‐glucose series, the picoloyl group exhibited minimal influence on stereoselectivity, with only weak nucleophiles showing a modest shift in selectivity for the 3‐O‐Pico protected glucosyl donor in comparison to the other C‐3‐acyl glucosides. In contrast, in the 3‐O‐picoloyl‐mannose series a much stronger β‐directing effect was observed, wherein more acidic acceptors led to increased β‐selectivity. The results provide insights into the complex interplay of acceptor acidity and glycosylation stereoselectivity mediated by the picoloyl protecting group.

show abstract

Neighboring‐Group Participation by C‐2 Acyloxy Groups: Influence of the Nucleophile and Acyl Group on the Stereochemical Outcome of Acetal Substitution Reactions

Cited by 5 publications

References 74 publications

Anomeric Triflates versus Dioxanium Ions: Different Product-Forming Intermediates from 3-Acyl Benzylidene Mannosyl and Glucosyl Donors

Anomeric Triflates versus Dioxanium Ions: Different Product-Forming Intermediates from 3-Acyl Benzylidene Mannosyl and Glucosyl Donors

Acetal Substitution Reactions: Stereoelectronic Effects, Conformational Analysis, Reactivity vs Selectivity, and Neighboring-Group Participation

The influence of acceptor acidity on hydrogen bond mediated aglycone delivery (HAD) through the picoloyl protecting group

Contact Info

Product

Resources

About