Secondary Allylic Alcohols Research Articles

Gold(I)−Catalyzed Synthesis of Cyclic Sulfamides via an Intramolecular Dehydrative Amination of Allylic Alcohols: A Strategy for 1,3‐Diamine Synthesis

AbstractA gold(I)‐catalyzed intramolecular dehydrative amination method has been developed to synthesize diverse cyclic sulfamides efficiently. Reactions proceed smoothly at room temperature using a combination of (IPr)AuCl (5 mol%) and AgBF4 (5 mol%). This method showcases a broad substrate scope, encompassing challenging seven‐membered ring structures, and exhibits functional group compatibility. Moreover, the reaction demonstrates high stereoselectivity, allowing the synthesis of enantiomerically enriched cyclic sulfamides from chiral secondary allylic alcohols. The synthesized cyclic sulfamides serve as valuable intermediates for generating 1,3‐diamines. This approach provides an improved route for cyclic sulfamide synthesis and a strategic entry point for obtaining essential 1,3‐diamine derivatives.

Brønsted Acid Catalyzed Dehydroxylative Cyanation of Benzylic Alcohols with Trimethylsilyl Cyanide Using 1,1,1,3,3,3‐Hexafluoro‐2‐propanol as a Solvent

AbstractA concise and direct Brønsted acid catalyzed cyanation of secondary and tertiary benzylic and allylic alcohols has been developed using trimethylsilyl cyanide (TMSCN) as a cyanide source and 1,1,1,3,3,3‐hexafluoro‐2‐propanol (HFIP) as a solvent. The present transition‐metal‐free catalytic process is operationally simple to perform under “open‐flask” conditions and is applicable to the preparation of a number of α‐arylacetonitriles as well as late‐stage material transformations. The effectiveness of the present protocol was further demonstrated by the first enantioselective synthesis and determination of the absolute configuration of verimol F.

Brønsted Acid Catalyzed Intramolecular Allylic Substitution Reaction of Allylic Alcohols: A Facile Synthesis of 2-Vinylchromans

AbstractBrønsted acid catalyzed intramolecular allylic substitution reaction of secondary and tertiary allylic alcohols has been developed. A variety of 2-vinylchromans were efficiently prepared in moderate to excellent yields. The given method features wide substrate scope, operational simplicity, and mild, metal-free reaction conditions. The practicability of the method was demonstrated by a gram-scale reaction and further derivations of the product. Preliminarily studies on a catalytic asymmetric reaction were also undertaken.

Deoxygenative 1,3-carbophosphination of allylic alcohols enabled by manganese pincer catalyst

The first manganese-catalyzed three-component coupling between secondary alcohol, allylic alcohol, and phosphine via borrowing hydrogen is described. This four-stage, one-pot reaction afforded ε-hydroxy phosphines in a step-economical fashion.

Palladium-Catalyzed C-H Allylation/Annulation Reaction of Amides and Allylic Alcohols: Regioselective Construction of Vinyl-Substituted 3,4-Dihydroisoquinolones.

A palladium-catalyzed highly regioselective C-H allylation/annulation reaction of N-sulfonyl amides with secondary or tertiary allylic alcohols has been developed to construct 3,4-dihydroisoquinolones bearing a synthetically valuable vinyl substituent. This cascade cyclization approach of allylic alcohols involving C-H allylation has not been reported previously. The commercially available allylic alcohol substrates, the only by-product of water, and the used terminal oxidant of O2 provide environmentally benign advantages.

Syn‐Selektive Epoxidierung von chiralen, terminalen Allylalkoholen mit einem Titan‐Salalen‐Katalysator und Wasserstoffperoxid

AbstractIn der asymmetrischen Sharpless‐Epoxidierung von chiralen, sekundären Allylalkoholen wird ein Substratenantiomer bevorzugt zum anti‐Epoxyalkohol umgesetzt. In dieser Arbeit stellen wir die erste hoch syn‐selektive Epoxidierung von terminalen Allylalkoholen vor. Mit einem Titan‐Salalen‐Katalysator und H2O2 als Oxidationsmittel werden enantiomerenreine, terminale Allylalkohole mit bis zu 98 % Ausbeute und >99 : 1 dr (syn) zu Epoxyalkoholen umgesetzt. Diese syn‐Selektivität bleibt auch bei niedrigeren Katalysatorbeladungen (bis zu 1 mol‐%) erhalten. Auch die Modifizierung der Allylalkoholfunktion zu einem Ether beeinflusst die Diastereoselektivität nicht [>99 : 1 dr (syn)]. Wird die Katalysatorkonfiguration invertiert, so wird bevorzugt das anti‐Produkt gebildet, allerdings mit niedrigerem dr (ca. 20 : 1). Das Anwendungspotential wird am Beispiel der Synthese eines THF‐Bausteins mit drei Stereozentren im Grammmaßstab demonstriert, in welcher zwei Ti‐Salalen‐katalysierte Epoxidierungen durchlaufen werden.

Syn‐Selective Epoxidation of Chiral Terminal Allylic Alcohols with a Titanium Salalen Catalyst and Hydrogen Peroxide

In the Sharpless asymmetric epoxidation of chiral secondary allylic alcohols, one substrate enantiomer is predominantly converted to the anti‐epoxy alcohol. We herein report the first highly syn‐selective epoxidation of terminal allylic alcohols using a titanium salalen complex as catalyst, at room temperature, and aqueous hydrogen peroxide as oxidant. With enantiopure terminal allylic alcohols as substrates, the epoxy alcohols were obtained with up to 98 % yield and up to >99 : 1 dr (syn). Catalyst loadings as low as 1 mol % can be applied without eroding the syn‐diastereoselectivity. Modification of the allylic alcohol to an ether does not affect the diastereoselectivity either [>99 : 1 dr (syn)]. Inverting the catalyst configuration leads to the anti‐product, albeit at lower dr (ca. 20 : 1). The synthetic potential is demonstrated by a short, gram‐scale preparation of a tetrahydrofuran building block with three stereocenters, involving two titanium salalen catalyzed epoxidation steps.

Manganese(I) catalyzed cross-coupling of secondary allylic alcohols and primary alcohols

Cross-coupling of alcohols to value-added products by using sustainable catalytic reactions has gained attention in recent years. Isomerization of secondary allylic alcohol to the corresponding enolizable ketone is an atom economical and known transformation. Herein, a selective cross-coupling of secondary allylic alcohol and primary alcohol is reported to afford the corresponding α-alkenyl or alkylation products. These catalytic protocols proceed via acceptorless dehydrogenative coupling (ADC) or borrowing hydrogen (BH) strategies, which liberates water and/or hydrogen as the only byproducts. Highly abundant manganese-based pincer catalysts catalyze the reactions.

N-Methyl Allylic Amines from Allylic Alcohols by Mitsunobu Substitution Using N-Boc Ethyl Oxamate.

We report the practical, scalable synthesis of a range of N-methyl allylic amines. Primary and secondary allylic alcohols underwent a regioselective Mitsunobu reaction with readily accessible N-Boc ethyl oxamate to deliver the corresponding N-Boc allylic amines, including in enantiopure form via stereospecific substitution. Subsequent N-methylation and Boc deprotection without chromatography yielded the amine products as hydrochloride salts. This method solves the problem of converting commercially available alcohols into often volatile N-methyl allylic amines, many of which have limited commercial availability.

A mild method for the replacement of a hydroxyl group by halogen: 3. the dichotomous behavior of α-haloenamines towards allylic and propargylic alcohols

A study of the deoxyhalogenation of allylic and propargylic alcohols with tetramethyl-α-halo-enamines is reported. Primary allylic and primary and secondary propargylic alcohols gave the corresponding halides in high yields. Secondary allylic and propargylic alcohols yielded the corresponding secondary halides but the reaction also produced some rearranged primary halides (I > Br > Cl). The reactions with tertiary allylic and tertiary propargylic alcohols gave several products and was therefore of little synthetic value. However, the addition of triethylamine to the reaction mixture or the use of lithium alkoxide instead of alcohol brought about a major change of the course of the reaction which led to amides carrying an allyl or an allenyl group at C 2 . This was shown to result from a Claisen-Eschenmoser rearrangement of an intermediate α-allyloxy- or propargyloxy-enamine.

Iridium-catalyzed C3-selective asymmetric allylation of 7-azaindoles with secondary allylic alcohols.

The development of efficient synthetic methods of 7-azaindoles has been desired due to the useful biological activities and physical properties. We report the first example of the iridium-catalyzed C3-selective asymmetric allylation of 7-azaindoles with racemic secondary allylic alcohols to give only branched allylation products in good to high yields with high enantioselectivity (up to >99.5% ee). Allylic alcohols and 7-azaindoles with a variety of functional groups including halogen and heteroaromatic groups are compatible with the reaction conditions. Furthermore, transformations of the obtained allylation products are demonstrated without a significant loss of enantiomeric excess.

Iridium-catalyzed regio- and enantioselective allylic esterification of secondary allylic alcohols with carboxylic acids.

We report herein an iridium-catalyzed asymmetric allylic esterification of racemic secondary allylic alcohols using free carboxylic acids as nucleophiles under mild conditions with broad functional group tolerance, exhibiting excellent regio- and enantioselectivity .

Chlorocyclization/cycloreversion of allylic alcohols to vinyl chlorides

Unprecedented chlorination of allylic alcohols: a simple mix-and-go procedure for the cyclization/cycloreversion of secondary and tertiary allylic alcohols with chloronium ions under mild conditions and practical access to remote carbonyl vinyl chlorides.

PQQ-dependent Dehydrogenase Enables One-pot Bi-enzymatic Enantio-convergent Biocatalytic Amination of Racemic sec-Allylic Alcohols.

The asymmetric amination of secondary racemic allylic alcohols bears several challenges like the reactivity of the bi‐functional substrate/product as well as of the α,β‐unsaturated ketone intermediate in an oxidation‐reductive amination sequence. Heading for a biocatalytic amination cascade with a minimal number of enzymes, an oxidation step was implemented relying on a single PQQ‐dependent dehydrogenase with low enantioselectivity. This enzyme allowed the oxidation of both enantiomers at the expense of iron(III) as oxidant. The stereoselective amination of the α,β‐unsaturated ketone intermediate was achieved with transaminases using 1‐phenylethylamine as formal reducing agent as well as nitrogen source. Choosing an appropriate transaminase, either the (R)‐ or (S)‐enantiomer was obtained in optically pure form (>98 % ee). The enantio‐convergent amination of the racemic allylic alcohols to one single allylic amine enantiomer was achieved in one pot in a sequential cascade.

Anti‐Markovnikov Hydroamination of Racemic Allylic Alcohols to Access Chiral γ‐Amino Alcohols

A ruthenium-catalyzed formal anti-Markovnikov hydroamination of allylic alcohols for the synthesis of chiral γ-amino alcohols is presented. Proceeding via an asymmetric hydrogen-borrowing process, the catalysis allows racemic secondary allylic alcohols to react with various amines, affording enantiomerically enriched chiral γ-amino alcohols with broad substrate scope and excellent enantioselectivities (68 examples, up to >99 % ee).

Anti‐Markovnikov Hydroamination of Racemic Allylic Alcohols to Access Chiral γ‐Amino Alcohols

AbstractA ruthenium‐catalyzed formal anti‐Markovnikov hydroamination of allylic alcohols for the synthesis of chiral γ‐amino alcohols is presented. Proceeding via an asymmetric hydrogen‐borrowing process, the catalysis allows racemic secondary allylic alcohols to react with various amines, affording enantiomerically enriched chiral γ‐amino alcohols with broad substrate scope and excellent enantioselectivities (68 examples, up to >99 % ee).

Synthesis of the Major Mammalian Metabolites of THCV.

A simple synthesis of the major oxidized metabolites in mammalian tissues of (-)-Δ9-tetrahydrocannabivarin (THCV) (1) has been accomplished by kinetic studies of allylic oxidation using SeO2 on botanically derived THCV with the aim to yield primary and secondary allylic alcohols concurrently. This synthetic approach led to the preparation of numerous THCV derivatives, including two new compounds, 8α-hydroxy-Δ9-tetrahydrocannabivarin (2) and 8β-hydroxy-Δ9-tetrahydrocannabivarin (3), and the known compounds 11-hydroxy-Δ9-tetrahydrocannabivarin (4) and Δ9-tetrahydrocannabivarin-11-oic acid (5), without affecting the C-10a stereogenic center in the natural precursor and without formation of tricyclic dibenzopyran derivatives. This simple synthetic methodology could be useful to investigate the pharmacological role of THCV metabolites at, among others, the endocannabinoid CB1 and CB2 receptors for which THCV reportedly acts as respectively a neutral antagonist and partial agonist.

One-pot two-step chemoenzymatic deracemization of allylic alcohols using laccases and alcohol dehydrogenases

A series of enantioenriched (hetero)aromatic secondary allylic alcohols has been synthesized through deracemization of the corresponding racemic mixtures combining a non-selective chemoenzymatic oxidation (laccase from Trametes versicolor and oxy-radical TEMPO) and a stereoselective biocatalyzed reduction (lyophilized cells of E. coli overexpressing an alcohol dehydrogenase, ADH). Both steps were performed in aqueous medium under very mild reaction conditions. After optimization, a sequential one-pot two-step protocol was set up, obtaining the corresponding chiral alcohols in moderate to high conversions (48–95%) and enantiomeric excess (65->99% ee). Depending on the ADH stereopreference, both antipodes from these valuable chiral synthons could be prepared, even at preparative scale (119−178 mg), in a straightforward manner.

Cover Feature: Rhodium‐Catalyzed Asymmetric [2+2+2] Cycloaddition of 1,6‐Enynes with Racemic Secondary Allylic Alcohols through Kinetic Resolution (Chem. Eur. J. 17/2020)

We have established that a cationic rhodium(I)/P-phos complex catalyzes the asymmetric [2+2+2] cycloaddition of 1,6-enynes with racemic secondary allylic alcohols to produce the corresponding chiral bicyclic cyclohexenes, possessing three stereogenic centers, as a single diastereomer with excellent ee values. Mechanistic experiments revealed that the present cycloaddition proceeds through the kinetic resolution of the racemic secondary allylic alcohols, in which one enantiomer preferentially reacts with the 1,6-enyne. This cover feature uses a mirror to portray how one enantiomer reacts preferentially over the other enantiomer. Also, the starry sky on the background is inspired by the structure of the bicyclic cyclohexene. More information can be found in the Communication by K. Tanaka et al. on page 3698.

Rhodium-Catalyzed Asymmetric [2+2+2] Cycloaddition of 1,6-Enynes with Racemic Secondary Allylic Alcohols through Kinetic Resolution.

It has been established that a cationic rhodium(I)/P-phos complex catalyzes the asymmetric [2+2+2] cycloaddition of 1,6-enynes with racemic secondary allylic alcohols to produce the corresponding chiral bicyclic cyclohexenes, possessing three stereogenic centers, as a single diastereomer with excellent ee values. Mechanistic experiments revealed that the present cycloaddition proceeds through the kinetic resolution of the racemic secondary allylic alcohols, in which one enantiomer preferentially reacts with the 1,6-enyne.