Asymmetric Transfer Hydrogenation of o-Hydroxyphenyl Ketones: Utilizing Directing Effects That Optimize the Asymmetric Synthesis of Challenging Alcohols

Abstract

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Escaping from Flatland: Stereoconvergent Synthesis of Three‐Dimensional Scaffolds via Ruthenium(II)‐Catalyzed Noyori–Ikariya Transfer Hydrogenation

“…The DKR–ATH of such 5‐methoxy‐4‐chromanones was highly stereoselective but required very high (30 mol %) loading of the catalyst ( R , R )‐ A to achieve >90 % conversions. peri ‐Methoxy‐benzofused ketones or o ‐methoxyacetophenones are known to be difficult substrates for ruthenium‐ and rhodium‐catalyzed transfer hydrogenation because the interaction with a Ru II ‐catalyst is hampered by the methoxy substituent [30] . This liability can generally be overcome by leading the synthesis via the hydroxy‐substituted ketones, the reduction of which is typically significantly more efficient compared to their methoxy analogs, [30, 31] or by switching to the catalyst G , which displays superior efficiency for the reduction of o ‐methoxyacetophenone [32] …”

“…peri-Methoxybenzofused ketoneso ro-methoxyacetophenones are known to be difficult substrates for ruthenium-and rhodium-catalyzed transfer hydrogenation because the interaction with aR u II -catalyst is hampered by the methoxy substituent. [30] This liability can generally be overcomeb yl eading the synthesis via the hydroxy-substitutedk etones, the reduction of which is typically significantly more efficient compared to their methoxy analogs, [30,31] or by switching to the catalyst G,w hich displays superior efficiency for the reduction of o-methoxyacetophenone. [32] Expanding the scope of the accessible stereopure 1,2,3-trisubstituted indans,w es tudied DKR-ATH of am odel 6-hydroxy-11H-indeno[1,2-c]quinolin-11-one 59 (Figure 15).…”

Asymmetric Transfer Hydrogenation of Aryl Heteroaryl Ketones using Noyori‐Ikariya Catalysts

“…This was also supported by the formation of S-17 (oOH/Im) under the same conditions, which, upon methylation was converted to S-16 (oOMe/Im). It has been demonstrated that ortho-hydroxyphenyl groups have a strong propensity to occupy the position near the catalyst η 6 -arene during ketone reduction (Figure 2C), [11] and the same selectivity is likely operating here. In contrast, ATH of substrate 22 containing two ortho-hydroxy groups failed (Figure 4).…”

Organocatalytic Discrimination of Non-Directing Aryl and Heteroaryl Groups: Enantioselective Synthesis of Bioactive Indole-Containing Triarylmethanes

“…[3][4] Asymmetric addition to the 1,1-diaryl C=C and C=X (X = heteroatom) bonds represents one of the most direct approaches for the construction of this unit. [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] However, this requires effective discrimination between two (often) sterically similar aryl groups, which represents a notable challenge in asymmetric catalysis (Fig 1b). 5 So far, success has mainly relied on the use of a directing group [6][7][8][9][10][11][12][13][14] in one aryl group to allow catalyst recognition (e.g., by coordination) or electronic difference by incorporating electron-donating/withdrawing groups 15,16 .Notably, the effective enantiodifferentiation between aryl and heteroaryl groups still remains challenging, particularly in the absence of a directing group or electronic manipulation.…”

“…[5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] However, this requires effective discrimination between two (often) sterically similar aryl groups, which represents a notable challenge in asymmetric catalysis (Fig 1b). 5 So far, success has mainly relied on the use of a directing group [6][7][8][9][10][11][12][13][14] in one aryl group to allow catalyst recognition (e.g., by coordination) or electronic difference by incorporating electron-donating/withdrawing groups 15,16 .Notably, the effective enantiodifferentiation between aryl and heteroaryl groups still remains challenging, particularly in the absence of a directing group or electronic manipulation. [17][18][19][20][21] Currently, successful differentiation between aryl and heteroaryl mostly involves a pyridine heterocycle due to its special coordinating ability.…”