Enantioselective Allylation Reaction Research Articles

Convergent and Enantioselective Total Synthesis of (−)-Amphidinolide O and (−)-Amphidinolide P

A convergent and enantioselective total synthesis of (-)-amphidinolide O (1) and P (2), 15-membered macrolides with seven chiral centers along with many functional groups, is described. The key reactions include enantioselective Brown allylation, anti- and syn-selective aldol reactions, (E)-selective olefin metathesis, conformation-controlled stereoselective epoxidation, and selective introduction of the exomethylene group. Assignments of the absolute stereochemistries of the natural (+)-amphidinolide O (ent-1) and P (ent-2) are also discussed in detail.

Low-Oxidation State Indium-Catalyzed C–C Bond Formation

The development of innovative metal catalysis for selective bond formation is an important task in organic chemistry. The group 13 metal indium is appealing for catalysis because indium-based reagents are minimally toxic, selective, and tolerant toward various functional groups. Among elements in this group, the most stable oxidation state is typically +3, but in molecules with larger group 13 atoms, the chemistry of the +1 oxidation state is also important. The use of indium(III) compounds in organic synthesis has been well-established as Lewis acid catalysts including asymmetric versions thereof. In contrast, only sporadic examples of the use of indium(I) as a stoichiometric reagent have been reported: to the best of our knowledge, our investigations represent the first synthetic method that uses a catalytic amount of indium(I). Depending on the nature of the ligand or the counteranion to which it is coordinated, indium(I) can act as both a Lewis acid and a Lewis base because it has both vacant p orbitals and a lone pair of electrons. This potential ambiphilicity may offer unique reactivity and unusual selectivity in synthesis and may have significant implications for catalysis, particularly for dual catalytic processes. We envisioned that indium(I) could be employed as a metallic Lewis base catalyst to activate Lewis acidic boron-based pronucleophiles for selective bond formation with suitable electrophiles. Alternatively, indium(I) could serve as an ambiphilic catalyst that activates both reagents at a single center. In this Account, we describe the development of low-oxidation state indium catalysts for carbon-carbon bond formation between boron-based pronucleophiles and various electrophiles. We discovered that indium(I) iodide was an excellent catalyst for α-selective allylations of C(sp(2)) electrophiles such as ketones and hydrazones. Using a combination of this low-oxidation state indium compound and a chiral semicorrin ligand, we developed catalytic highly enantioselective allylation, crotylation, and α-chloroallylation reactions of hydrazones. These transformations proceeded with rare constitutional selectivities and remarkable diastereoselectivities. Furthermore, indium(I) triflate served as the most effective catalyst for allylations and propargylations of C(sp(3)) electrophiles such as O,O-acetals, N,O-aminals, and ethers, and we applied this methodology to carbohydrate chemistry. In addition, a catalyst system composed of indium(I) chloride and a chiral silver BINOL-phosphate facilitated the highly enantioselective allylation and allenylation of N,O-aminals. Overall, these discoveries demonstrate the versatility, efficiency, and sensitivity of low-oxidation state indium catalysts in organic synthesis.

Catalytic Enantioselective 1,2‐Diboration of 1,3‐Dienes: Versatile Reagents for Stereoselective Allylation

More with boron: The development of catalytic enantioselective 1,2-diboration of 1,3-dienes enables a new strategy for enantioselective carbonyl allylation reactions (see scheme). These reactions occur with outstanding levels of stereoselection and can be applied to both monosubstituted and 1,1-disubstituted dienes. The carbonyl allylation reactions provide enantiomerically enriched functionalized homoallylic alcohol products.

ChemInform Abstract: An Enantioselective Indium-Mediated Allylation Reaction of Aldehydes and Ketones in Dichloromethane.

Abstract An enantioselective indium-mediated addition reaction of allylic bromides to carbonyl compounds was achieved in dichloromethane in the presence of (−)-cinchonidine. The desired products were obtained in moderate to excellent yields and with up to 75% enantioselectivity.

ChemInform Abstract: Chiral Diphenylthiophosphoramides: A New Class of Chiral Ligands for the Silver(I)-Promoted Enantioselective Allylation of Aldehydes.

Abstract Chiral C2-symmetric diphenylthiophosphoramides 1 and 2 were prepared in high yields from the reaction of diphenylthiophosphinic chloride with (1R,2R)-(−)-1,2-diaminocyclohexane and (1R,2R)-(+)-1,2-diphenylethylenediamine, respectively. Another novel chiral ligand 4 was prepared from reaction of diphenylthiophosphinic chloride with (R)-(+)-1,1′-binaphthyl-2,2′-diamine using butyllithium as a base. They were used as catalytic chiral ligands in the silver(I)-promoted enantioselective allylation reaction of aldehydes with allyltributyltin.

Total synthesis of (+)-papulacandin D

A total synthesis of (+)-papulacandin D has been achieved in 31 steps, in a 9.2% overall yield from commercially available materials. The synthetic strategy divided the molecule into two nearly equal sized subunits, the spirocyclic C-arylglycopyranoside and the polyunsaturated fatty acid side-chain. The C-arylglycopyranoside was prepared in 11 steps in a 30% overall yield from triacetoxyglucal. The fatty acid side-chain was also prepared in 11 steps in a 30% overall yield from geraniol. The key strategic transformations in the synthesis are: (1) a palladium-catalyzed, organosilanolate-based cross-coupling reaction of a dimethylglucal-silanol with an electron-rich and sterically hindered aromatic iodide and (2) a Lewis-base catalyzed, enantioselective allylation reaction of a dienal and allyltrichlorosilane. A critical element in the successful execution of the synthesis was the development of a suitable protecting group strategy that satisfied a number of stringent criteria.

Unexpected effect of the fluorine atom on the optimal ligand-to-palladium ratio in the enantioselective Pd-catalyzed allylation reaction of fluorinated enol carbonates

The enantioselective Pd-catalyzed allylation reaction of fluorinated allyl enol carbonates is presented; a key feature of this transformation is the important effect of the ligand-to-palladium ratio on the enantioselectivity of the alpha-fluoroketones, since using a ligand excess (L/Pd ratio = 1.25 : 1) led to moderate results (30-76% ee), while using a L/Pd ratio <1 : 1.67 (to as low as 1 : 4) allowed the desired products to be obtained with high enantiopurity (up to 94% ee).

Application of iridium catalyzed allylic substitution reactions in the synthesis of branched tryptamines and homologues via tandem hydroformylation–Fischer indole synthesis

Combination of enantioselective allylation reactions with a tandem hydroformylation-Fischer indole synthesis sequence as a highly diversity-oriented strategy for the synthesis of tryptamines and homologues was explored. This modular approach allows the substituents at C3 of the indole core, the type of the amine moiety, and the distance of the amine moiety to the indole core in the final synthetic step to be defined. The starting materials required for the hydroformylation step were synthesized via iridium catalyzed enantioselective allylic substitution reactions in high yields and excellent enantioselectivities. The Rh catalyzed hydroformylation step in the presence of phenyl hydrazine, allows the in situ formed aldehyde to be trapped as the hydrazone. Subsequent acid catalyzed indolization furnishes the desired indole structures in moderate to good yields.

Enantioselective Pd-Catalyzed Allylation Reaction of Fluorinated Silyl Enol Ethers

An enantioselective Pd-catalyzed allylation reaction of fluorinated silyl enol ethers is reported. This reaction provides a stereoselective and efficient approach to allylated tertiary α-fluoroketones from achiral fluorinated precursors. A variety of cyclic silyl enol ether can be used, and the yields of the desired products range from 52 to 93%, and the enantiomeric excesses range from 83 to 95% ee.

Chiral (S)‐(+) 1‐Substituted Aryl‐4‐(1‐phenyl) Ethylformamido‐5‐amino‐1,2,3‐triazole: A New Class of Chiral Ligands for the Silver(I)‐Promoted Enantioselective Allylation of Aldehydes

Some novel chiral ligands, (S)‐(+) 1‐substituted aryl‐4‐(1‐phenyl) ethylformamido‐5‐amino‐1,2,3‐triazoles, were prepared starting from 1‐substituted aryl‐4‐ethoxycarbonyl‐5‐amino‐1,2,3‐triazoles and other reagents. They were used as catalytic chiral ligands in the silver (I)‐promoted enantioselective allylation reaction of aldehydes with allyltributyltin.

Concise Asymmetric Total Synthesis of Obolactone

The first efficient asymmetric synthesis of obolactone 1 has been accomplished in 11 steps and with a 15% overall yield in which Brown's enantioselective allylation reactions and ring-closing metathesis reaction are key steps.

Silver-Catalyzed Asymmetric Sakurai−Hosomi Allylation of Ketones

The complex of AgF and (R)-DIFLUORPHOS has been shown to be an effective catalyst for the asymmetric Sakurai-Hosomi allylation of simple ketones. A significaant improvement of the reactivity was observed by using THF as the solvent. The catalyst turnover was increased by addition of 1 equiv of MeOH. AgF and (R)-DIFLUORPHOS predominantly formed a 1:1 complex that provided high enantioselectivity. This catalyst system can be applied to various simple ketones, and corresponding tertiary homoallylic alcohols were obtained with excellent enantioselectivities (up to 96% ee). Only 1,2-adducts were obtained from both acyclic and cyclic conjugate ketones. The regio-, diastereo-, and enantioselective crotylation has also been achieved. E- or Z-crotyltrimethoxysilane gave a similar diastereomer ratio with high enantioselectivities. This finding introduces the utility of racemic allylsilanes for the enantioselective Sakurai-Hosomi allylation reaction.

Enantioselective radical allylation reactions using chiral lanthanide Lewis acids

Radical additions to oxazolidinone acrylate followed by allyl trapping were studied with chiral Lewis acids derived from lanthanide salts. Chiral ligands were evaluated to establish the α-stereocenter. Ligands with a prolinol framework along with achiral additives proved to be effective. The observed trends are compared with those in the literature.

Highly Enantioselective Allylation of Arylaldehydes Catalyzed by a Silver(I)‐Chiral Binaphthylthiophosphoramide.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Highly Enantioselective Allylation of Arylaldehydes Catalyzed by a Silver(I)‐Chiral Binaphthylthiophosphoramide

AbstractChiral diphenylthiophosphoramide L2 prepared from diphenylthiophosphinic chloride and (R)‐(+)‐N‐ethyl‐1,1′‐binaphthyl‐2,2′‐diamine 2 was used as a catalytic chiral ligand in the silver(I)‐catalyzed enantioselective allylation reaction of arylaldehydes with allyltributyltin to furnish high ee (up to 98%) of the homoallylic alcohols. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2003)

Understanding the correlation of structure and selectivity in the chiral-phosphoramide-catalyzed enantioselective allylation reactions: solution and solid-state structural studies of bisphosphoramide.SnCl(4) complexes.

Complexation of bisphosphoramides, linked by various length methylene tethers, with tin tetrachloride was studied by both solution NMR spectroscopy and single-crystal X-ray crystallography. The formation of cis-configured, octahedral 1/1 bisphosphoramide.SnCl(4) complexes was supported by both crystallographic and solution NMR studies. In addition, the formation of such complexes was shown to be highly dependent on the tether length and solution concentration. Single-crystal X-ray analysis of bisphosphoramide.SnCl(4) complexes also provided detailed information on the stereochemical environment relevant to the enantioselectivity of asymmetric allylation reactions.

Synthesis of Aminophosphine Ligands with Binaphthyl Backbones for Silver(I)‐catalyzed Enantioselective Allylation of Benzaldehyde†

AbstractA series of aminophosphine ligands was synthesized from 2‐amino‐2′‐hydroxy‐1,1′‐binaphthyl (NOBIN). Their asymmetric induction efficiency was examined for silver(I) catalyzed enantioselective allylation reaction of benzaldehyde with allyltributyltin. Under the optimized reaction conditions, quantitative yield as well as moderate ee value (54.5% ee) of product was achieved by the catalysis with silver(I)/3 complex. The effects of the binaphthyl backbone and the substitutes situated at chelating N, P atoms on enantioselectivity of the reaction were also discussed.

ChemInform Abstract: A Catalytic Enantioselective Allylation Reaction of Aldehydes in an Aqueous Medium.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

A catalytic enantioselective allylation reaction of aldehydes in an aqueous medium

A modified Yamamoto–Yanagisawa's catalyst ( S)-Tol-BINAP·AgNO 3 was successfully applied to a catalytic enantioselective allylation reaction of aldehydes in an aqueous system. The reactions with aromatic aldehydes afforded the desired products in high yields with good stereoselectivities.

Chiral diphenylthiophosphoramides: a new class of chiral ligands for the silver(I)-promoted enantioselective allylation of aldehydes

Chiral C 2-symmetric diphenylthiophosphoramides 1 and 2 were prepared in high yields from the reaction of diphenylthiophosphinic chloride with (1 R,2 R)-(−)-1,2-diaminocyclohexane and (1 R,2 R)-(+)-1,2-diphenylethylenediamine, respectively. Another novel chiral ligand 4 was prepared from reaction of diphenylthiophosphinic chloride with ( R)-(+)-1,1′-binaphthyl-2,2′-diamine using butyllithium as a base. They were used as catalytic chiral ligands in the silver(I)-promoted enantioselective allylation reaction of aldehydes with allyltributyltin.