Photo‐induced Substitutive Introduction of the Aldoxime Functional Group to Carbon Chains: A Formal Formylation of Non‐Acidic C(sp³)−H Bonds

Abstract

A photo‐induced substitutive introduction of an aldoxime functional group to carbon chains was achieved using photo‐excited 4‐benzoylpyridine as a C(sp3)−H bond cleaving agent and arylsulfonyl oxime as an aldoxime precursor. The non‐acidic C−H bonds in various substances, including cycloalkanes, ethers, azacycles, and cyclic sulfides, were chemoselectively converted at ambient temperature under neutral conditions. The present transformation is a formal formylation of non‐acidic C(sp3)−H bonds in a single step.

A General Photocatalytic Route to Prenylation

“…Zard[13c] has explored lauroyl peroxide mediated allylation of xanthate esters with α‐substituted allylic alkyl sulfones, which suggests it should be possible to use sulfones. Furthermore, more recently Ollivier, Kamijo, Zhu, Chen and Flechsig have shown that photocatalytically generated radicals can react with a range of sulfonyl reagents which are capable of trapping radicals, suggesting that it might be possible to identify a prenyl transfer reagent capable of working under photocatalytic conditions. Thus, we synthesized and tested a library of isoprenyl sulfones ( 1j – 1q ).…”

Morpholine As a Scaffold in Medicinal Chemistry: An Update on Synthetic Strategies

“…The α‐amino functionalization of morpholines via a radical mediated photo‐induced coupling, was initially developed by the Hoffmann group and then explored further by Kamijo and co‐workers. These reactions require the photoactive reagent either in catalytic (Scheme B−D) or stoichiometric (Scheme E) amounts. However, the need for 5 to 8 equivalents of the morpholine coupling partner is the main disadvantage of these methods, limiting their potential wider use in drug discovery projects.…”

“… A direct photo‐catalyzed C−H vinylation ( A ) and examples of photoredox α‐amino functionalization methodologies ( B – E ). Reagents and conditions : a) Ir[dF(CF3)ppy]2(dtbbpy)PF6 (1 mol %), CsOAc, DCE, 26 W fluorescent light, rt (yield: 79 %); b) 4,4’‐dimethoxybenzophenone (10 mol %), hv (350 nm), dithiocarbamate, MeCN (yield: 70 %); c) 5,7,12,14‐pentacenetetrone (5 mol %), hv (365 nm LED lamp), K 2 CO 3 , rt, 24 h (yield: 60 %); d) 2‐chloroanthraquinone (10 mol %), hv (365 nm Hg lamp), DCM, rt, 4 h (yield: 48 %); e) Ph 2 CO (1 equiv), hv (medium pressure Hg lamp), t ‐BuOH, rt, 1 h (yield: 98 %)]; (Bn: benzene).…”

“…After the abovementioned studies, a number of groups further researched the development of photoredox α-amino functionalization methodologies applicable to morpholines, by using iridium catalysts alone (Scheme 26A), [81] or in conjunction with another catalyst such as a transition state metal [82][83] or an organocatalyst, [84] as demonstrated in representative examples shown in Scheme 26BÀ E. The α-amino functionalization of morpholines via a radical mediated photo-induced coupling, was initially developed by the Hoffmann group and then explored further by Kamijo and co-workers. These reactions require the photoactive reagent either in catalytic (Scheme 26BÀ D) [85][86][87] or stoichiometric (Scheme 26E) [88] amounts. However, the need for 5 to 8 equivalents of the morpholine coupling partner is the main disadvantage of these methods, limiting their potential wider use in drug discovery projects.…”

“…[80] (DMA: N,Ndimethylacetamide, ppy: 2-phenylpyridine, dtbbpy: 4,4'-di-tert-butyl-2,2'bipyridine). [85] c) 5,7,12,14pentacenetetrone (5 mol %), hv (365 nm LED lamp), K 2 CO 3 , rt, 24 h (yield: 60 %); [86] d) 2-chloroanthraquinone (10 mol %), hv (365 nm Hg lamp), DCM, rt, A more recent report by the MacMillan group refers to CÀ H arylation of N-Boc-morpholine, mainly on the α-amino position. In this approach, generation of the carbon-centered radical is followed by a Ni-catalyzed cross-coupling reaction with an aryl bromide, resulting in CÀ C products with sp 3 hybridization.…”