Uracil-Cu(i) catalyst: allylation of cyclopropanols with Morita-Baylis-Hillman alcohols under water-tolerant conditions.

Inspired by the high affinity of copper with DNA and RNA, a uracil-copper catalytic system was developed to promote ring-opening allylation of cyclopropanols with allylic alcohols under water-tolerant conditions. A new C-OH bond-breaking model can well resolve the trade-off between the need for acidic activators for C(allyl)-OH bond cleavage and the demand for strong basic conditions for generating homoenolates. Therefore, Morita-Baylis-Hillman alcohols, rather than their pre-activated versions, could be incorporated directly into dehydrative cross-coupling with cyclopropanols delivering water as the only by-product. A variety of functionalized δ,ε-unsaturated ketones were obtained in good-to-high yield with high E-selectivity.

Sulfination of Unactivated Allylic Alcohols via Sulfinate-Sulfone Rearrangement.

A dehydrative cross-coupling of unactivated allylic alcohols with sulfinic acids was achieved under catalyst-free conditions. This reaction proceeded via allyl sulfination and concomitant allyl sulfinate-sulfone rearrangement. Various allylic sulfones could be obtained in good to excellent yields with water as the only byproduct. This study expands the synthetic toolbox for constructing allylic sulfone molecules.

Fluoroalkylation of Activated Allylic Acetates through Radical-Radical Coupling: Organophotoredox/DABCO Catalytic System.

A novel organophotoredox/DABCO catalytic system for the fluoroalkylation of activated allylic acetates via radical-radical coupling is described. The method offers mild reaction conditions, high selectivity, and broad substrate compatibility and enabled diverse bioactive molecules, FDA-approved drugs, and amino acid derivatives to be incorporated into transformation. This study expands the synthetic toolbox for the construction of fluorine-containing molecules.

Organophotoredox-Catalyzed Intermolecular Formal Grob Fragmentation of Cyclic Alcohols with Activated Allylic Acetates.

We have developed an efficient method that employs organophotoredox-catalyzed relay Grob fragmentation to facilitate the smooth ring-opening allylation of cyclic alcohols in an environmentally friendly manner. This protocol directly incorporates a wide spectrum of cyclic alcohols and activated allylic acetates into the cross-coupling reaction, eliminating the need for metal catalysts. The process yields a variety of distally unsaturated ketones with good to excellent outcomes and stereoselectivity, while acetic acid is the sole byproduct.

One-Pot and Unsymmetrical Bis-Allylation of Malononitrile with Conjugated Dienes and Allylic Alcohols.

A Pd/Ca catalytic system to promote the unsymmetrical bis-allylation of malononitrile was developed by selecting conjugated dienes and allylic alcohols as allylic reagents. This catalytic system suppressed the competitive symmetrical bis-allylation process and guaranteed the desired unsymmetrical bis-allylation with high chemoselectivity. A wide range of conjugated dienes and allylic alcohols were tolerated well in this transformation, and diverse 1,6-dienes were obtained with high efficiency.

Dehydrative Cross-Coupling for C-N Bond Construction under Transition-Metal-Free Conditions.

A transition-metal-free catalytic system was designed to address the dehydrative cross-coupling of unactivated primary/secondary alcohols with amines/amides under environmentally benign conditions. Mg2+ and counteranion (PF6-) worked synergistically to realize C-OH bond cleavage and concomitant C-N bond formation. A wide range of allylic alcohols and amines/amides were tolerated well in this transformation, which allowed C-N bond construction with high efficiency.

Visible-Light-Induced Trifluoromethylation of Allylic Alcohols.

An organic photoredox-catalyzed dehydroxylative trifluoromethylation of allylic alcohols was developed in an environmentally benign manner. In this reaction, the readily available CF3SO2Na was selected as the trifluoromethylation reagent. The in situ generated byproduct SO2 was reutilized to activate C-OH bond, which enabled this dehydroxylative trifluoromethylation to be performed conveniently. A variety of multifunctionalized CF3-allylic compounds were obtained in high yields and excellent stereoselectivity.

Dehydrative Allylation of Alkenyl sp2 C-H Bonds.

We designed a cooperative catalytic system by combining commercially available Ca(NTf2)PF6 and Pd(PPh3)4 to address the dehydrative allylation of alkenyl sp2 C-H bonds in an environmentally benign manner. A novel C-OH bond cleavage method was found to be crucial for this practical protocol. A variety of alkenes and allylic alcohols equipped with wide-spectrum functional groups can be successfully incorporated into the desired cross-coupling, affording 1,4-dienes with moderate to excellent yields and high stereo- and regioselectivity.

Reciprocal-Activation Strategy for Allylic Sulfination with Unactivated Allylic Alcohols.

A reciprocal-activation strategy for allylic sulfination with unactivated allylic alcohols was developed. In this reaction, the hydrogen bond interaction between allylic alcohols and sulfinic acids allowed for reciprocal activation, which enabled a dehydrative cross-coupling process to occur under mild reaction conditions. This reaction worked in an environmentally friendly manner, yielding water as the only byproduct. A variety of allylic sulfones could be obtained in good to excellent yields with wide functional group tolerance. In gram scale reactions, allylic sulfones could be conveniently isolated in high yield by filtration.

Dehydrative Cross-Coupling of Allylic Alcohols with Alkynes.

A highly efficient Pd/Ca catalytic system for the directly dehydrative cross-coupling of allylic alcohols with terminal alkynes was developed. This calcium salt cocatalyst facilitates the oxidative addition of the palladium catalyst (1 mol %) to the C-OH bond. Then, the in situ-generated hydroxide ion deprotonates the terminal alkynes to promote the formation of the allylalkynylpalladium intermediate, liberating water as the only byproduct. This proposed mechanism is also supported by density functional theory calculations. An anticancer agent was prepared from inexpensive starting materials on a 10 g scale.

Alkaline-Earth Metal Catalyzed Dehydrative Allylic Alkylation.

An alkaline-earth metal catalytic system for environmentally benign allylic alkylation was developed. Allylic alcohols can be utilized directly at room temperature in this transition-metal-free process, producing water as the only byproduct. A variety of allylic compounds, including the ones containing all-carbonyl quaternary centers, can be obtained with high yields.

A Ba/Pd Catalytic System Enables Dehydrative Cross-Coupling and Excellent E-Selective Wittig Reactions.

A Ba/Pd cooperative catalysis system was developed to enable the dehydrative cross-coupling of allylic alcohols with P-ylides to occur directly and promote a subsequent Wittig reaction in one pot. A variety of multisubstituted 1,4-dienes were isolated in good to excellent yields with broad P-ylides (stabilized by both ester and ketone carbonyl groups) and aldehyde (aliphatic and aromatic) substrates with excellent E selectivity.

Allylic Phosphorus Ylides Directly Generated from Alcohols with Water as the Only Byproduct.

A novel strategy for the preparation of allylic phosphorus ylides directly from Morita-Baylis-Hillman (MBH) alcohols in an environmentally benign manner was developed. With the assistance of a calcium catalyst, the SN2' process between phosphines and allylic alcohols occurred smoothly, delivering allylic phosphorus salts and calcium-stabilized hydroxide ions. Then, in situ deprotonation gave the allylic phosphorus ylides with water as the only byproduct. Functionalized 1,3-diene moieties can be conveniently obtained by trapping the ylides through a Wittig olefination.

Barium-catalyzed C-OH/P-H dehydrative cross-coupling for C-P bond construction.

A barium-catalyzed C-OH/P-H dehydrative cross-coupling protocol for the construction of C-P bonds was developed. This reaction was performed in an environmentally benign manner with water as the only by-product. A variety of allylic phosphorus compounds can be isolated in good to excellent yields.

Direct Substitution of Secondary and Tertiary Alcohols To Generate Sulfones under Catalyst- and Additive-Free Conditions.

An environmentally benign protocol that affords propargylic sulfones containing highly congested carbon centers from easily accessible alcohols and sulfinic acids with water as the only byproduct is reported. The reaction proceeded via an in situ dehydrative cross-coupling process by taking advantage of the synergetic actions of multiple hydrogen bonds rather than relying on an external catalyst and/or additives to achieve high product distribution.

Bronsted Acid/Organic Photoredox Cooperative Catalysis: Easy Access to Tri- and Tetrasubstituted Alkenylphosphorus Compounds from Alcohols and P-H Species.

A Bronsted acid/organic photoredox cooperative catalytic system toward P-C bond formation from alcohols and P-H species is developed. With the assistance of visible light and TBHP, the reactions proceeded smoothly in an environmentally benign manner to give various alkenylphosphorus compounds in high efficiency.

Water-promoted C-S bond formation reactions.

Allylic sulfones, owning to their widespread distributions in biologically active molecules, received increasing attention in the past few years. However, the synthetic method under mild conditions is still a challenging task. In this paper, we report a sulfinic acids ligation with allylic alcohols via metal-free dehydrative cross-coupling. Both aliphatic and aromatic sulfinic acids react with various allylic alcohols to deliver the desired allylic sulfones in high yields with excellent selectivity. This carbon-sulfur bond formation reaction is highly efficient and practical since it works under metal-free, neutral, aqueous media and at room temperature in which the products even can be obtained by simple filtration without the need for organic extraction or column chromatography. Water is found to be essential for the success of this carbon-sulfur bond formation reaction. DFT calculations imply that water acts as promoter in this transformation via intermolecular hydrogen bonds.

Asymmetric P-C Bond Formation: Diastereoselective Synthesis of Adjacent P,C-Stereogenic Allylic Phosphorus Compounds.

A novel catalytic asymmetric P-C bond formation between phosphinates/phosphine oxide and allylic carbonates was developed. This methodology could not only afford a variety of functionalized adjacent P,C-stereogenic phosphorus compounds in high yields with high regio- and diastereoselectivities but also provide an alternative strategy to access enantiomerically enriched (SP )-phosphinates through kinetic resolution.

Zinc Amide Catalyzed Regioselective Allenylation and Propargylation of Ketones with Allenyl Boronate.

Zinc amide catalyzed, regioselective allenylation and propargylation of ketones with allenyl boronate is reported. Tertiary allenyl and homopropargyl alcohols were obtained, respectively, in high selectivities, from the same starting materials, simply by changing the reaction conditions. The substrate scope was wide. Mechanistic studies suggest that the reactions are controlled under kinetic and thermodynamic conditions.

Morita-Baylis-Hillman adduct derivatives (MBHADs): versatile reactivity in Lewis base-promoted annulation.

Lewis base-promoted annulation reactions with MBHADs have emerged as a key platform for the construction of functionalized carbo- and heterocycles. MBHADs, which are economical and readily available, exert diverse and amazing reactivity when reacted with a wide range of electrophiles. A variety of carbo- and heterocycles, most of which are predominant in natural products and pharmaceuticals, could be constructed with high efficiency. This tutorial review will describe these annulation reactions, with a special emphasis on recent work regarding diverse reactivities of MBHADs.