Selective oxidation of benzylic and allylic alcohols using Mn(OAc)3/catalytic 2,3-dichloro-5,6-dicyano-1,4-benzoquinone

A practical, chemoselective oxidation of alcohols employing catalytic quantities of DDQ as the oxidant and Mn(OAc)(3) as the co-oxidant is described. Electron-rich benzylic alcohols are oxidized efficiently to their corresponding carbonyls, but less electron-rich benzylic alcohols remain unchanged. Allylic alcohols are rapidly oxidized to their corresponding aldehyde or ketone counterparts in high yields. This protocol is operationally simple, employs an inexpensive source of Mn(OAc)(3), has short reaction times, and exhibits a significant chemoselectivity favoring allylic alcohols over benzylic alcohols. This procedure also avoids the use of very large excesses of reagents and sometimes poor reproducibility that characterize previously developed reagents such as MnO(2).     

Cyclohexene Promoted Efficient Biomimetic Oxidation of Alcohols to Carbonyl Compounds Catalyzed by Manganese Porphyrin under Mild Conditions

Selective oxidation of alcohols to corresponding carbonyl compounds is one of the most important processes both in academic and application research. As a kind of biomimetic catalyst, metalloporphyrins‐catalyzed aerobic oxidation of alcohols with aldehyde as hydrogen donator is gathering much attention. However, using olefins as another kind hydrogen donator for aerobic oxidation of alcohols has not been reported. In this study, a system comprising managenese porphyrin and cyclohexene for biomimetic aerobic oxidation of alcohols to carbonyl compounds was developed. The catalytic system exhibited excellent catalytic performance and selectivity towards the corresponding products for most primary and secondary alcohols under mild conditions. Based on the results obtained from experiments as well as in situ EPR (electron paramagnetic resonance) and UV‐vis spectroscopy, the role of cyclohexene was demonstrated.     

CuCl catalyzed selective oxidation of primary alcohols to carboxylic acids with tert-butyl hydroperoxide at room temperature

Direct oxidation of primary alcohols to the corresponding carboxylic acids is performed highly efficiently at room temperature with anhydrous tert-butyl hydroperoxide in the presence of a catalytic amount of easily available CuCl under ligand free conditions in acetonitrile. Benzylic alcohols are more reactive than aliphatic alcohols, and these benzylic alcohols are selectively oxidized to the corresponding acids in the presence of aliphatic alcohols such as 1-octanol and 1-decanol.     

Functionalized Resins for the Synthesis of Peptide Alcohols

Peptide alcohols are clinically important compounds that are underexplored in structure–activity relationship (SAR) studies in drug discovery. One reason for this underutilization is that current syntheses are laborious and time consuming. Herein, we describe the preparation and utility of Rink, Ramage, and Sieber-chloride resins, which enables the use of a general, easy and practical method for the attachment of fluorenylmethoxycarbonyl (Fmoc)-amino alcohols to a solid support, in the synthesis of peptide alcohols. This method is the first straightforward Fmoc/tBu synthesis of peptide alcohols starting from a pre-loaded resin. The synthesized peptide alcohols can be detached from the linkers through conventional methods. Treatment with trifluoroacetic acid (TFA) (95 %) and scavengers such as triisopropylsilane and water for 2 h is sufficient to obtain a fully deprotected peptide alcohol, while treatment with 20 % hexafluoroisopropanol in dichloromethane renders a fully protected peptide alcohol that can be further modified at the C-terminus. As examples, the new resins were used in straightforward, relatively rapid syntheses of the peptide alcohols octreotide, alamethicin, and a segment of trichogin GA IV, as well as the first synthesis of stapled peptide alcohols.     

Oxygen transfer from sulfoxides: selective oxidation of alcohols catalyzed by polyoxomolybdates

Benzylic, allylic, and aliphatic alcohols are oxidized to aldehydes and ketones in a reaction catalyzed by Keggin-type polyoxomolybdates, PV(x)Mo(12-x)O(40)(-(3+x)) (x = 0, 2), with DMSO as a solvent. The oxidation of benzylic alcohols is quantitative within hours and selective, whereas that of allylic alcohols is less selective. Oxidation of aliphatic alcohols is slower but selective. Further mechanistic studies revealed that, for H(3)PMo(12)O(40) as a catalyst and benzylic alcohols as substrates, the sulfoxide is in fact an oxygen donor in the reaction. Postulated reaction steps as determined from isotope-labeling experiments, kinetic isotope effects, and Hammett plots include (a) sulfoxide activation by complexation to the polyoxometalate and (b) oxygen transfer from the activated sulfoxide and elimination of water from the alcohol. The mechanism is supported by the reaction kinetics.     

Efficient selective oxidation of alcohols to aldehydes catalyzed by a morpholinone nitroxide

Efficient chemoselective oxidation of primary alcohols to the corresponding aldehydes is described. The transformation is promoted by a catalytic morpholinone nitroxide radical catalyst which can be easily synthesized. A broad range of substrates including aromatic and aliphatic primary alcohols are converted with excellent yields under mild conditions. The control experiments reveal that the morpholinone nitroxide can be used as a selective oxidant for primary alcohols in the presence of secondary alcohols.     

N-溴代丁二酰亚胺水相氧化醇类化合物反应研究

以水为反应介质、NBS为氧化剂,在水相无催化剂条件下实现了醇的氧化.芳香醇、脂肪醇都可以达到95%以上的醛(或酮)产率,但该体系对一些含供电子取代基的醇的反应活性不高,选用salen-Co(Ⅲ)配合物作为催化剂,可拓宽反应的底物适用范围.     

Transition-Metal-Catalyzed Direct Substitution of Alcohols in Aqueous Media

The direct use of alcohols as the much greener and more sustainable alkylated reagents in substitution reactions is one of the emerging areas in green chemisty. However, owing to the poor leaving character of OH group, the direct substitution of alcohols is not an easy thing. Transition metal (TM) catalysis such as Pd-catalyzed allylic/benzyl substitution and Ir-catalyzed borrowing hydrogen provides efficient protocols for the direct substitution of alcohols, however, an organic solvent and servely anhydrous conditions are generally required. In recent decade, TM-catalyzed direct substitution of alcohols in aqueous media was developed as a much greener alternative. In this review, the recent develpoments of this area are summarized. The activation mechanism of alcohols in aqueous reactions are emphatically discussed.     

Copper‐Catalyzed Trifluoromethylation of Trisubstituted Allylic and Homoallylic Alcohols

An efficient copper‐catalyzed trifluoromethylation of trisubstituted allylic and homoallylic alcohols with Togni’s reagent has been developed. This strategy, accompanied by a double‐bond migration, leads to various branched CF₃‐substituted alcohols by using readily available trisubstituted cyclic/acyclic alcohols as substrates. Moreover, for alcohols in which β‐H elimination is prohibited, CF₃‐containing oxetanes are isolated as the sole product.     

Highly selective 1,3-isomerization of allylic alcohols via rhenium oxo catalysis

Two reaction strategies are developed to promote the highly selective 1,3-isomerization of a variety of allylic alcohols using O3ReOSiPh3 as a catalyst. The first strategy utilizes substrates whose 1,3-regioisomer contains a conjugated alkene, which relies on thermodynamics to obtain high selectivity. The second strategy employs N,O-bis(trimethylsilyl)acetamide as an additive to selectively and irreversibly remove the product from the reaction equilibrium and works well for the isomerization of tertiary allylic alcohols into primary allylic alcohols containing trisubstituted alkene components. High stereoselectivity is also observed in the 1,3-isomerization of enantioenriched allylic alcohols.     

β-Arylation of Racemic Secondary Benzylic Alcohols to Access Enantioenriched β-Arylated Alcohols

The transformation of alcohols into value-added products is of great importance, as simple alcohols are widespread and can be easily derived from both fossil fuels and biomass. The selective functionalization of a sp³ C−H bond on the alkyl side chain of an alcohol over its hydroxyl group would offer an expedient route to expand the chemical space of alcohols but it remains a challenging task. Harnessing the borrowing hydrogen strategy, the β-arylation of secondary alcohols with aryl bromides has been achieved in this study, which allows for the selective functionalization of a β-Csp³−H bond in an alcohol substrate. Under the catalysis of a Pd complex, secondary alcohols reacted with aryl bromides to afford 1,2-diaryl alcohols with broad substrate scope in the presence of a ketone additive. Furthermore, the enantioconvergent version of the reaction has also been realized, transforming racemic secondary alcohols into enantioenriched chiral 1,2-diaryl alcohols under the cooperative Pd and Ru catalysis. Mechanism studies indicate that the reactions are enabled by borrowing hydrogen catalysis.     

Enantioselective oxidation of racemic secondary alcohols catalyzed by chiral Mn(III)-salen complexes with N-bromosuccinimide as a powerful oxidant

We demonstrate an efficient enantioselective oxidation of secondary alcohols catalyzed by Mn(III)-salen complex using N-bromosuccinimide (NBS) as the oxidant. The new protocol is very efficient for the oxidative kinetic resolution of a variety of secondary alcohols, including ortho-substituted benzylic alcohols.     

Barium dichromate [BaCr2O7], a mild reagent for oxidation of alcohols to their corresponding carbonyls in non-aqueous polar aprotic media

Barium dichromate is used as a mild oxidizing agent for the selective conversion of primary and secondary alcohols to their corresponding aldehydes and ketones, respectively. Over-oxidation does not occur and primary alcohols undergo oxidation to the aldehyde. Primary and secondary benzylic alcohols are oxidized faster and more efficiently.     

AgOTf catalyzed direct amination of benzyl alcohols with sulfonamides

AgOTf catalyzed direct amination of primary alcohols with sulfonamides is described. This effective catalyst requires no preactivation of the hydroxy group of alcohols and the reaction is environmentally benign with water as a by-product. Various primary alcohols on amination with sulfonamides gave the corresponding products in moderate to good yields.     

仲醇的氧化动力学拆分

光学活性仲醇是非常重要的合成多种具有药物和生物活性化合物的原料和关键中间体,它们可通过外消旋仲醇的氧化动力学拆分获得。本文按氧化剂和手性催化剂的类别分类综述了近年来通过氧化动力学拆分获得光学活性仲醇方法的进展,并对一些方法的机理进行了描述。对以(-)-金雀花碱-钯(Ⅱ)、金雀花碱类似物-钯(Ⅱ)、N-杂环卡宾(NHC)-钯(Ⅱ)、手性双官能团-铱配合物以及手性(ON)-钌(salen)配合物催化的分子氧为氧化剂的仲醇的氧化动力学拆分进行了充分讨论。此外,还讨论了手性salen-锰(Ⅲ)催化二乙酰基碘苯以及通过不对称氢转移的方法对仲醇的氧化动力拆分。可以发现,(-)-金雀花碱-钯(Ⅱ)-分子氧体系在目前所有仲醇氧化动力学拆分体系中表现最佳。用于仲醇氧化动力学拆分的高效体系仍有待进一步开发。     

Practical Cu(OAc)2/TEMPO-catalyzed selective aerobic alcohol oxidation under ambient conditions in aqueous acetonitrile

We reported a ligand- and additive-free Cu(OAc)₂/TEMPO catalyst system that enables efficient and selective aerobic oxidation of a broad range of primary and secondary benzylic alcohols, primary and secondary 1-heteroaryl alcohols, cinnamyl alcohols, and aliphatic alcohols to the corresponding aldehydes and ketones. This ambient temperature oxidation protocol is of practical features like aqueous acetonitrile as solvent, ambient air as the terminal oxidant, and low catalyst loading, presenting a potential value in terms of both economical and environmental considerations. Based on the experimental observations, a plausible reaction mechanism was proposed.     

无催化剂下醇和酚的高效O-硅基化

硅醚类化合物广泛应用于有机合成、 分离分析和精细化工等领域. 六甲基二氮硅烷是近年来发展的一种新型硅基化试剂, 被用于硅醚的高效合成, 但由于六甲基硅烷较为惰性, 通常需要加入催化剂活化. 本文报道了一种无催化剂下醇、 酚的高效硅基化新方法. 研究结果表明, 该方法可以兼容一级苄醇、 杂芳基苄醇、 脂肪醇, 二级醇甚至三级醇, 多数反应可以实现定量转化, 无需柱层析即可实现产物的分离纯化. 该方法可以拓展到酚的高效硅醚化, 也可以很方便地放大到100 mmol, 收率达到99%, 表明该方法具有较好的实用价值.     

DMSO-catalyzed chlorination of alcohols using N-phenylbenzimidoyl chloride

N-phenylbenzimidoyl chloride has been demonstrated as an efficient chlorination reagent catalyzed by dimethyl sulfoxide (DMSO) in conversion of alcohols to corresponding chlorides. The reaction conditions were mild, and most of the substrates gave satisfactory yields. The configuration inversion of the chlorination was proved using optically active phenyl alcohols. The amount of DMSO can be as low as 0.001 eq without reducing the efficiency of the chlorination. A plausible mechanism for the reaction was proposed and proved by experiments. The reaction is stereoselective and potentially chemoselective among primary benzyl alcohols, secondary benzyl alcohols, and unactivated aliphatic alcohols.     

Facile One-pot Transformation of 2,3-Epoxy Alcohols into Allylic Alcohols

Optically-active allylic alcohols have been frequently used as chiral building blocks for the preparation of optically pure compounds.¹ There are at present various methods for the synthesis of optically active allylic alcohols including the kinetic resolution racemic allylic alcohols,² reductive rearrangement of 2,3-epoxy alcohol by metal, halide and telluium-based chemistry.³ To our knowledge, One-pot Transformation of 2,3-epoxy alcohols into allylic alcohols, especially via epoxy iodides,is limited to Dorta's method³ using a Ph₃P,iodine, imidazole,2,6-lutidine and water system. The original Dorta's method can be successfully applied to the formation of tertiary allylic alcohols, but give unsatisfactory results in formation of secondary allylic alcohols.     

N-thioacyl 1,3-amino alcohols: synthesis via ring-opening of oxiranes with thioamide dianions and applications as key intermediates leading to stereochemically defined 5,6-dihydro-4H-1,3-oxazines and 1,3-amino alcohols

N-Thioacyl 1,3-amino alcohols were synthesized via the ring-opening of oxiranes with thioamide dianions generated from N-benzyl thioamides and BuLi in a highly regio- and stereoselective manner. The diastereomers of N-thioacyl 1,3-amino alcohols were readily separated by column chromatography to give stereochemically defined N-thioacyl 1,3-amino alcohols. They underwent intramolecular cyclization with Bu4F and EtI to give 5,6-dihydro-4H-1,3-oxazines. The reaction was specific with anti-N-thioacyl 1,3-amino alcohols, and cis-5,6-dihydro-4H-1,3-oxazines were obtained with high efficiency, whereas the reaction of a syn-alcohol gave a thioimidate as a major product. The reduction of N-thioacyl 1,3-amino alcohols with LiAlH4gave N-alkyl 1,3-amino alcohols in high yields. The use of optically active propylene oxide as a starting material gave the corresponding oxazine and alcohols in optically pure forms.