Hf(IV)-catalyzed enantioselective epoxidation of N-alkenyl sulfonamides and N-tosyl imines

Asymmetric epoxidation of allylic and homoallylic amine derivatives catalyzed by Hf(IV)-bishydroxamic acid complexes is described. Under similar conditions, aldimine and ketimine produced oxaziridines. The sulfonyl group is demonstrated to be an effective directing group for these transformations.     

The asymmetric aminohydroxylation route to GABOB and homoserine derivatives

The 4-nitrophenyl ether is an efficient directing group in the asymmetric aminohydroxylation reaction of homoallylic ether derivatives. Either regioisomeric product can be obtained with useful levels of enantioselectivity allowing for the short enantioselective synthesis of GABOB and homoserine derivatives. A model based on substrate-catalyst interactions is presented to explain the regio- and enantioselectivity of the aminohydroxylation reactions.     

Diastereoselective allylation of planar chiral substituted ferrocenecarboxaldehyde: an efficient entry to chiral ferrocenyl ligands

2,2′-Disubstituted ferrocenecarboxaldehydes are subjected to zinc-mediated allylation to form homoallylic ferrocenyl alcohols. The effects of ortho-substituted functional groups on facial selectivities of planar chiral aldehydes were studied and it was found that the corresponding homoallylic alcohols were obtained as single diastereomers in excellent yields.     

Stereoselective VO(acac)(2) Catalyzed Epoxidation of Acyclic Homoallylic Diols. Complementary Preparation of C2-syn-3,4-Epoxy Alcohols

A substrate-controlled stereoselective epoxidation of free and monoprotected homoallylic diols was developed. This second-generation approach is based on the incorporation of a primary hydroxy directing group at the C2 methyl carbon, which changes the nature of the vanadium ester intermediate providing a new diastereoselectivity manifold for the preparation of 3,4-epoxy alcohols. This modification favored the formation of the challenging C2-syn epoxy alcohol product not previously available using the standard homoallylic alcohol substrates. These new epoxy alcohol diastereomers expand the scope and generality for the utilization of 3,4-epoxy alcohols as precursors for stereoselective polypropionate synthesis.     

Directing abilities of alcohol-derived functional groups in the hydroformylation of olefins

The hydroformylation of allylic and homoallylic alcohols and their derivatives using cationic and neutral rhodium complexes has been examined. The highest diastereoselectivity (87:13) was observed in the reaction of 1-methoxymethoxy-2-methylenecyclohexane. Higher yields and similar selectivities were obtained in the reaction of the TBDMS-protected alcohol. The major diastereomer results from hydroformylation syn to the functional group, which would suggest a directing effect. However, hydroformylation of 3-methylene-1-cyclohexanol derivatives occurs on the face opposite to the directing group in the major isomer. These data, in addition to the results of hydroformylation of 1-methyl-2-methylenecyclohexane, suggest that inherent conformational preferences are of significant importance in determining the product distribution and that the directing power of simple alcohols and their derivatives is moderate at best under the conditions examined in this study.     

Alpha-phosphono lactone analogues of cytidine and cytosine arabinoside diphosphates: synthesis via ring closing metathesis

alpha-Phosphono lactone derivatives of the nucleosides cytidine and cytosine arabinoside have been prepared from the corresponding nucleoside aldehydes. The stereochemical outcome of allylation reactions with these aldehydes was found to be dependent upon both the choice of protecting groups for the 2'- and 3'-hydroxyl groups and, to some extent, the nature of the Lewis acid catalyst employed. Ultimately, conditions were found that favored either the 5'R or 5'S diastereomer from different cytidine aldehydes, and gave some stereoselectivity in additions to an aldehyde derivative of ara-C. The resulting homoallylic alcohols were used as substrates in attempted Knovenagel and Horner-Wadsworth-Emmons condensations, but elimination was found to predominate over lactone formation under the conditions employed. The desired alpha-phosphono lactones could be prepared through a reaction sequence that included ring-closing metathesis on acrylate esters of the homoallylic alcohols, followed by reduction of the resulting alpha,beta-unsaturated lactones and carbon-phosphorus bond formation on enolates generated from the saturated lactones.     

Surprising stereoselectivity in the Payne epoxidation of terpinen-4-ol with acetonitrile/hydrogen peroxide

A surprisingly high level of cis-stereoselectivity in the Payne epoxidation has been identified with the homoallylic alcohol, terpinen-4-ol. Very high efficiencies for hydrogen peroxide are realized under mild conditions. The necessity for peroxyimidic acid stabilization by solvent is replaced by coordination to the directing hydroxyl function, resulting in dramatically improved space yields at up to the one kilogram scale.     

Regio- and enantioselective intermolecular hydroacylation: substrate-directed addition of salicylaldehydes to homoallylic sulfides

We report a Rh-catalyzed, regio- and enantioselective intermolecular olefin hydroacylation under mild conditions. Hydroacylations between homoallylic sulfides, containing a substrate-bound directing group, and salicylaldehyde derivatives occur in the presence of a spiro-phosphoramidite ligand, (R)-SIPHOS-PE, to give α-branched ketones in >20:1 selectivity and up to 97% ee. Our conditions are also applicable to the asymmetric intermolecular hydroacylation of 1,2-disubstituted olefins.     

Access to chiral homoallylic vicinal diols from carbonyl allylation of aldehydes with allyl ethers via palladium-catalyzed allylic C-H borylation

Chiral homoallylic vicinal diols are found in many bioactive compounds and are among the most versatile functional groups in organic chemistry. Here, we describe an asymmetric carbonyl allylation of aldehydes with allyl ethers proceeding via allylic C-H borylation enabled by palladium and chiral phosphoric acid sequential catalysis, providing facile access to homoallylic vicinal anti-diols in high yields and with excellent stereoselectivity. This protocol enables the total synthesis of aigialomycin D to be finished within 7 steps.     

Lewis Acid-Mediated Decarboxylative Allylation of Enol Carbonates

A homoallylic ketone can be transformed and functionalized by various synthetic reactions, and thus, is regarded as one of the representative building blocks in organic chemistry. An additional route to access homoallylic ketones, namely, a Lewis acid-mediated decarboxylative allylation of cyclic enol carbonates, prepared by fixation of carbon dioxide onto propargyl alcohols, was developed in this work. The treatment of a cyclic enol carbonate with a Lewis acid in the presence of an allylsilane resulted in the formation of a homoallylic ketone. It was found that the title reaction proceeded well by the combined use of zirconium tetrachloride with allyltrimethylsilane. The allylation occurred with high regioselectivity and the corresponding homoallylic ketones were obtained in good-to-high yields. A reaction mechanism involving the decarboxylative formation of an oxyallyl cation equivalent is proposed.     

Peracid dependent stereoselectivity and functional group contribution to the stereocontrol of epoxidation of (E)-alkene dipeptide isosteres

Twelve Boc-protected phenylalanyl-phenylalanine and phenylalanyl-glycine trans-vinyl isosteres were epoxidised with magnesium monoperoxyphtalate hexahydrate (MMPP) and trifluoroperacetic acid, and the results have been compared with those from earlier studies on epoxidations with m-CPBA. The alkenes were synthesised in high yields with high E/Z-selectivities using either the Julia or Schlosser reactions. The formation of threo isomers was favoured in all epoxidation reactions except with CF₃CO₃H on substrates containing two allylic/homoallylic functional groups directing the peracid to opposite faces of the alkene. The switch to erythro selectivity observed with CF₃CO₃H is suggested to emanate from coordination to the allylic ester functionalities via hydrogen bond donation from the peracid. The other peracid reagents seem to be preferentially coordinated to the allylic carbamate function. The contribution of individual functional groups to the stereopreference was also investigated.     

SnCl2／Cu-Mediated Carbonyl Allylation Reaction in Water： Scope, Selectivity and Mechanism

Copper was found to be able to promote the SnC12-mediated carbonyl allylation reactions in water, giving the corresponding homoallylic alcohol products in very high yields. Detailed studies showed that the reaction could be applied to a variety of carbonyl compounds including those with hydroxyl, amino and nitro groups. It was also found that this reaction showed good regioselectivities for some substrates. Furthermore, carefully controled experiments and in situ NMR measurements provided important insights into the mechanism of the newly developed reaction.     

Synthesis of homoallylic amines and acylhydrazides by tin powder‐promoted multicomponent one‐pot allylation reactions

An efficient process for the synthesis of homoallylic amines and N′‐homoallylic hydrazides is developed from the one‐pot reaction of carbonyl compounds, amines or N‐acylhydrazines, allyllic bromide and tin powder using water as solvent. N‐Acylhydrazines are found to be more reactive than amines in these processes. They can react not only with aldehydes but also with ketones to give the corresponding N′‐homoallylic hydrazides. Copyright © 2016 John Wiley & Sons, Ltd.     

Enantioselective transfer aminoallylation: synthesis of optically active homoallylic primary amines

A camphorquinone-derived chiral homoallylic amine was found to react with various aldehydes via imine formation and asymmetric 2-azonia-Cope rearrangement to give optically active homoallylic primary amines. A practical level of enantioselectivity with high functional group tolerance has been attained in this transformation.     

Cyclization by intramolecular carbolithiation of alkyl- and vinyllithiums prepared by reductive lithiation: surprising stereochemistry in the lithium oxyanion accelerated cyclization

The versatility of intramolecular carbolithiation of simple alkenes to yield cyclopentylmethyllithiums by unconjugated organolithiums is greatly increased (1) by generating the organolithiums by reductive lithiation of phenyl thioethers with aromatic radical anions and (2) by using allylic or homoallylic alcohol groups on the receiving alkene. This type of reductive lithiation allows virtually any kind of organolithium to be generated, usually in a connective manner. Furthermore, the allylic or homoallylic lithium oxyanionic groups on the alkene greatly accelerate the reactions and lead in most cases to completely stereoselective cyclization at -78 degrees . Most significantly, the trans stereoselectivity is the opposite from that observed when the organometallic is allylic. A four-membered ring has also been generated by this method.     

Highly stereoselective synthesis of homoallylic amines based on addition of allyltrichlorosilanes to benzoylhydrazones

Allyltrichlorosilanes reacted with benzoylhydrazones in DMF without the use of any catalyst to afford the corresponding homoallylic benzoylhydrazines in good to high yields. The reactions proceeded at 0 degrees C to room temperature under mild conditions. In addition, it was found that the reactions tolerated well the steric hindrance of hydrazones and allyltrichlorosilanes. Indeed, ketone-derived benzoylhydrazones reacted with allyltrichlorosilane smoothly to afford the corresponding N'-tert-alkyl-N-benzoylhydrazines in high yields. In crotylation with (E)- and (Z)-crotyltrichlorosilanes, syn- and anti-adducts were stereospecifically obtained, respectively. These reactions are most likely to proceed via a cyclic chairlike transition state where the R group takes an axial position. When alpha-heteroatom-substituted chiral benzoylhydrazones were used, high anti-diastereoselectivities were observed. These adducts can be readily converted to homoallylic amines in high yields without epimerization.     

Achieving Vinylic Selectivity in Mizoroki–Heck Reaction of Cyclic Olefins

In Heck reactions of cyclic olefins, the products usually have aryl groups that end up at the allylic and/or homoallylic position. We herein report new selectivity that adds aryl groups to the vinylic position. Cyclic olefins of various ring size worked well. The desired isomers were produced by palladium–hydride‐catalyzed isomerization of the initial products. Thus, a specific catalyst must be used so that it can perform two jobs under one set of reaction conditions.     

Palladium(0)/indium iodide-mediated allylations of electrophiles generated from the hydrolysis of Eschenmoser’s salt: one-pot preparation of diverse carbocyclic scaffolds

A formyl equivalent was generated in situ from Eschenmoser’s salt in aqueous THF and was reacted with an allylindium species. Acylnitroso-derived hetero-Diels-Alder adducts and related allyl acetates were shown to be substrates for Pd(0)/InI-mediated allylations of formaldehyde-related species to provide homoallylic alcohols. Hydroxymethyl groups were installed with regio- and diastereocontrol to provide relevant disubstituted carbocyclic scaffolds. Enantiopure anti-disubstituted cyclopentene products were prepared from a chiral allyl acetate.     

Carboncarbon bond formation using bismuth in a water medium

In the presence of bismuth and ammonium chloride, allyl halides were found to react with aldehydes in a water medium at room temperature to give the corresponding homoallylic alcohols.     

Metallic bismuth mediated allylation of aldehydes to homoallylic alcohols

In the presence of metallic bismuth, allyl halides were found to react with aldehydes under mild conditions to give the corresponding homoallylic alcohols in good yields.