Adjacent Stereocenters Research Articles

A domino copper-catalyzed C-O coupling-Claisen rearrangement process.

A practical method for the diastereoselective generation of two adjacent quarternary stereocenters by combining a copper-catalyzed C-O coupling reaction with a subsequent Claisen rearrangement in a one-pot domino process is described. Furthermore, an experimentally simple method for the stereoselective synthesis of a variety of different types of vinyl ethers is delineated using the same catalyst system.

Stereoselective oxymercuration of cyclopropylcarbinols with anchimeric assistance by aromatic groups

Cyclopropylcarbinols bearing an adjacent stereocenter substituted by a phenyl group undergo anchimerically assisted mercurations, leading after reductive demercuration to oxygenated heterocycles or acyclic alcohols depending on the relative configurations.

Chiral amino ether-controlled catalytic enantioselective arylthiol conjugate additions to alpha,beta-unsaturated esters and ketones: scope, structural requirements, and mechanistic implications.

Asymmetric conjugate addition reaction of 2-trimethylsilylbenzenethiol with enoates and enones is catalyzed by a chiral amino ether-lithium thiolate complex and affords adducts with high enantioselectivity. Both the s-cis conformation and a steric wall at one side of the carbonyl group are structural requirements in substrates yielding adducts with high enantioselectivity. Reactions with tert-butyl enones gave addition products with high enantioselectivity. Construction of two contiguous chiral centers was possible by this addition-protonation sequence. Methyl tiglate was stereoselectively converted to a single syn-adduct of 95% enantiomeric excess (ee) bearing two contiguous chiral centers. Methyl 2-phenyl-2-butenoate was converted to a single syn-adduct of 95% ee, which was desulfurized to methyl 2-phenylbutanoate of 95% ee. These additions generate a transient lithium enolate that is protonated by a thiol anti to the C-S bond, giving the corresponding product having two adjacent stereocenters.

Synthesis of stereotriads by oxymercuration of substituted cyclopropylcarbinols.

[structure: see text] Cyclopropylcarbinol derivatives bearing an adjacent methyl-substituted stereocenter and a remote beta-hydroxy group protected as a pivalate underwent anchimerically assisted regio- and diastereoselective oxymercurations, affording after reductive demercuration, an access to stereotriads.

Asymmetric allylboration and ring closing alkene metathesis: a novel strategy for the synthesis of glycosphingolipids.

A novel strategy for the synthesis of D,L-glucosylceramide 1, a member of the glycosphingolipid class of natural products is described. Reagent-controlled asymmetric Brown allylboration gave excellent stereochemical control in the construction of adjacent stereocenters in the sphingoid base portion of the molecule. The trans-configured double bond was obtained as a single geometrical isomer by use of silicon-tethered olefin metathesis employing the Schrock carbene [(CF3)2MeCO]2Mo(=CHCMe2Ph)(=NC6H3-2,6-i-Pr2++ +) and in situ PhLi-induced ring-opening of the intermediate 5,6-dihydro-2H-1,2-oxasiline followed by protodesilylation with TBAF in DMSO. The synthesis was completed by long chain amide formation and global deprotection.

Highly Diastereoselective Synthesis of Monocyclic and Bicyclic Secondary Diorganozinc Reagents with Defined Configuration

Configurationally stable secondary diorganozinc reagents with three adjacent stereocenters can be prepared with high diastereoselectivity by a reaction sequence comprising a substrate-controlled hydroboration and a boron–zinc exchange (see scheme). After a second transmetalation numerous cyclic products are accessible by reaction with various electrophiles.

Diastereoselective Ortho-Metalation of Stereogenic Ferrocenylphosphine Oxides. Asymmetric Synthesis of the First Enantiopure Phosphorus-Chiral 2,2‘-Bis(diarylphosphino)-1,1‘-biferrocenyls

Two novel phosphorus-chiral ligands, 2,2‘-bis(arylphenylphosphino)-1,1‘-biferrocenyls 1a (aryl = 1-naphthyl) and 1b (aryl = 2-biphenylyl), have been prepared in enantiopure form by stereoselective multistep synthesis. While asymmetry on phosphorus was established via nucleophilic substitution reactions at borane-protected phosphorus centers, ortho-iodination of the derived optically pure ferrocenylphosphine oxides served as the key step for the introduction of planar chirality. Utilizing biphenylylphenylphosphinoxyferrocene, 5b, the latter reaction was found to proceed in a highly diastereoselective manner, resulting in a product distribution of 97:3. The absolute configuration of the predominantly formed diastereomer was confirmed by crystal structure analysis of the Ullmann-coupled bis(arylphenylphosphinoxy)biferrocenyl 6b (aryl = biphenylyl). Reduction of dioxides 6a (aryl = 1-naphthyl) and 6b gave rise to the enantiopure C2-symmetrical title compounds comprising four adjacent stereocenters. The coordi...

Catalytic Asymmetric Epoxidation Using a Fructose-Derived Catalyst

Modern epoxidation methods are able to create two adjacent stereocenters with very high enantioselectivity. Opening of the epoxides with nucleophiles permits rapid entry into complex organic systems, making this powerful synthetic methodology one of the fundamental reactions in organic synthesis. Various reagents for generating epoxides have been developed, including the dioxiranes. These oxidants are typically generated in situ from a ketone. Recently, a chiral dioxirane has been prepared from fructose and shown to catalytically deliver an oxygen from a simple, symmetrical oxidant to a wide variety of alkenes in very high yields and with excellent selectivity. This reaction makes an effective experiment for advanced undergraduates. Both the synthesis of the catalyst and the epoxide product are easily purified and lend themselves well to analysis by the standard array of techniques available to the organic chemist. Enantioselectivity can be determined either by polarimetry or by NMR shift experiments. In addition, the mechanism of the asymmetric epoxidation can be explored by a combination of computer modeling and student-proposed research experiments.

Stereoselective Synthesis of Cyclopropanes Bearing Adjacent Stereocenters

Stereoselective Synthesis of Cyclopropanes Bearing Adjacent Stereocenters

Stereoselective Allylic C-H Activation with Tertiary Alkylboranes: A New Method for Preparing Cycloalkyl Derivatives with Three Adjacent Stereocenters.

A regio- and stereoselective migration takes place under mild conditions for tertiary organoboranes obtained by hydroboration of tetrasubstituted cyclic alkenes. A subsequent amination proceeds with perfect control of the stereochemistry. The scheme shows an example of this for the reaction of bicyclo[4.3.0]non-1(6)-ene (1) to 2 via intermediates 3 and 4. Compound 2 is formed as the single diastereomer in 69% yield.

Total Synthesis of the Nonadjacent Bis-Tetrahydrofuran Annonaceous Acetogenin Squamostatin-D.

A total synthesis of the Annonaceous acetogenin squamostatin-D is described. Key adjacent stereocenters were introduced through enantioselective addition of chiral oxygenated allylic tin and indium reagents to aldehyde subunits. The isolated stereocenter at C12 was constructed through addition of a functionalized organozinc reagent to an aldehyde subunit in the presence of a chiral bis-sulfonamide-titanium catalyst.

Tandem [4 + 2]/[3 + 2] Cycloadditions of Nitroalkenes. 9. Synthesis of (−)-Rosmarinecine

(−)-Rosmarinecine (2) is the necine base portion of the pyrrolizidine alkaloid (−)-rosmarinine. (−)-Rosmarinecine is a representative of the group of pyrrolizidines that show a cis relationship between adjacent stereocenters C(1), C(7), and C(7a), in addition to a highly oxygenated skeleton. (−)-Rosmarinecine (2) has been synthesized in eight steps and 14.8% overall yield, as an illustration of a general approach for the construction of pyrrolizidines having this stereochemical feature. The key step in the asymmetric synthesis is a Lewis acid-promoted, tandem inter-[4 + 2]/intra-[3 + 2] cycloaddition between a fumaroyloxy nitroalkene and a chiral vinyl ether.

Stereoselective construction of quaternary centers at ambient temperature by the highly stereocontrolled migration of groups containing sp-, sp2-, and sp3-hybridized carbon atoms

A very highly diastereoselective semipinacol rearrangement of 2,3-epoxy alcohol mediated by tin-(IV) chloride at ambient temperatures is shown to be applicable to a wide variety of migrating groups including methyl, tert-butyl, cyclopropyl; vinyl, alkynyl, phenyl, and 2-furyl. A synthetically valuable feature is that a mixture of syn- and anti-epoxy alcohol affords only a single diastereoisomerically pure β-hydroxy ketone. Additional advantages of the reaction include the presence in the product of two adjacent stereocenters and the efficient creation of a new quaternary center, valuable features in the synthesis of a variety of natural products