Asymmetric Addition of Allylsilanes to Aldehydes – A Cr/Photoredox Dual Catalytic Approach Complementing the Hosomi–Sakurai Reaction

Abstract

The allylation of aldehydes is a fundamental transformation in synthetic organic chemistry. Among the multitude of available reagents, especially allylsilanes have been established as preferred allyl source. As initially reported by Hosomi & Sakurai, these non-toxic and highly stable reagents add to carbonyls via an open transition state upon Lewis acid activation. Herein, we report a general strategy to access a variety of valuable homoallylic alcohols in opposite chemo- and diastereoselectivity to the established Hosomi–Sakurai conditions by switching to photocatalytic activation in combination with a closed transition state (Chromium catalysis). Moreover, this dual catalytic approach displays a straightforward way to introduce excellent levels of enantioselectivity and its mild conditions allow for a broad substrate scope including chiral boron-substituted products as a highlight. To emphasize the synthetic utility, our method was applied as the key step in the synthesis of a bioactive compound and in the late-stage functionalization of steroid derivatives. Detailed mechanistic studies and DFT calculations hint towards an unprecedented photo-initiated chain being operative.

Merging Carbonyl Addition with Photocatalysis

“…By using a visible-light-mediated dual catalytic approach to coupling allylsilanes 97 with aldehydes 96, our group achieved high levels of selectivity (Scheme 6). 56 Using a suitable organophotocatalyst initially developed by our group 15 and a chiral ligand originally introduced by Kanai's group, 16 homoallylic alcohols 98−99 could be generated in high yields that a formal σ-bond metathesis may take place, which is supported by an in-depth DFT study.…”

“…47 By employing catalytic amounts of 4CzIPN and CrCl 2 , homoallylic alcohols 55 could be formed from suitable aldehydes 52, Hantzsch esters 53, and 1,3-dienes 54 under visible-light irradiation (Scheme 4). Both aliphatic and aromatic aldehydes, featuring protected amines (56,59), free alcohols (57), ethers (58), halides, and alkenes, were all tolerated in this multicomponent reaction. Various 4-alkyl Hantzsch esters and 1,3-dienes were also investigated in the current system, delivering the corresponding products in good to excellent yields and diastereoselectivities.…”

“…By using a visible-light-mediated dual catalytic approach to coupling allylsilanes 97 with aldehydes 96 , our group achieved high levels of selectivity (Scheme ). Using a suitable organophotocatalyst initially developed by our group and a chiral ligand originally introduced by Kanai’s group, homoallylic alcohols 98–99 could be generated in high yields and enantioselectivities. Both aromatic ( 104 – 106 ) and aliphatic aldehydes ( 100 – 103 , 107 – 109 ) showed remarkable reactivity, even in the presence of a variety of functional groups.…”

Chromium/Photoredox Dual Catalyzed Synthesis of α‐Benzylic Alcohols, Isochromanones, 1,2‐Oxy Alcohols and 1,2‐Thio Alcohols

“…This nucleophilic species chemoselectively adds to the aldehyde leading to the formation of chromium alkoxide C. Afterwards, the TMS + (where [TMS + ] shows a possible solvated/coordinated cage) generated within the oxidation step is most likely to mediate the [CrÀ O]-bond breakage. [41] The cycle continues after the Cr III gets reduced back again to Cr II (E 1/2 (Cr III /Cr II ) = À 0.51 V vs SCE in DMF), [33] with simultaneous regeneration of PC1 (E red = À 0.536 V vs SCE in MeCN) [29] in its ground state. Another possible route could be the direct nucleophilic addition of Crspecies B to TMS + -coordinated carbonyl.…”

Chrom/Photoredox‐dualkatalysierte Synthese von α‐benzylischen Alkoholen, Isochromanonen, 1,2‐Oxyalkoholen und 1,2‐Thioalkoholen

“…Erstens deuten die Stern-Volmer Lumineszenz Löschungsstudien darauf hin, dass alle untersuchten Klassen von Silylsubstraten die Lumineszenz von Photokatalysator PC1 löschen, was mit einer zuvor berichteten Studie übereinstimmt (Abbildung 7A). [28] Die Raten sind jedoch wie folgt: [41] Der Zyklus setzt sich fort, nachdem Cr III wieder zu Cr II reduziert wurde (E 1/2 (Cr III /Cr II ) = À 0.51 V vs SCE in DMF). [33] mit gleichzeitiger Regeneration von PC1 (E red = À 0.536 V vs SCE in MeCN) [29]…”