Enantioselective Synthesis of (−)-Dihydrocodeinone: A Short Formal Synthesis of (−)-Morphine^1,^†

The radical cyclization approach to the morphine alkaloids has been applied in an asymmetric synthesis of (−)-dihydrocodeinone. A chiral cyclohexenol (R-32), from the CBS reduction of the enone, is the source of chirality. The first key step, tandem closure in which stereochemistry is controlled by geometric constraints, (−)-15b → (+)-16, was followed by an unprecedented reductive hydroamination, completing the synthesis of (−)-dihydroisocodeine ((−)-17) in 13 steps from commercially available materials

Asymmetric Catalysis Route to <i>anti</i>,<i>anti</i> Stereotriads, Illustrated by Applications

A short sequence based on asymmetric catalysis, chirality transfer, and an optimized carbometallation protocol gave an anti,anti stereotriad building block in six steps. Both enantiomers of the chirality source, N-methyl ephedrine, are inexpensive, and the auxiliary is recoverable. In one chiral series, the building block was converted to the “B-2” intermediate in Miyashita's synthesis of scytophycin C; in the enantiomeric series, it was converted to a key intermediate for aplyronine A and to the polyketide “cap” for the callipeltins

Scalable, Catalytic Asymmetric Synthesis of Syn, Anti Stereotriad Building Blocks for Polypropionate Antibiotics

Asymmetric catalysis and chirality transfer by the 2,3-Wittig rearrangement were combined to provide a syn, anti stereotriad-containing olefinic alcohol in five steps from inexpensive starting materials. Development of this compound, a versatile intermediate for polypropionate synthesis, gave known building blocks for discodermolide

Short Synthesis of the C1−C14 Stretch of Discodermolide from Building Blocks Prepared by Asymmetric Catalysis

A convergent and stereoselective synthesis of the C1−C14 stretch of (+)-discodermolide demonstrates the utility of the “asymmetric catalysis approach” to complex polypropionates. The preparation of this complex synthon requires 15 steps in the longest linear sequence and 19 steps total from inexpensive materials

Scalable, Catalytic Asymmetric Synthesis of Syn, Anti Stereotriad Building Blocks for Polypropionate Antibiotics

Asymmetric catalysis and chirality transfer by the 2,3-Wittig rearrangement were combined to provide a syn, anti stereotriad-containing olefinic alcohol in five steps from inexpensive starting materials. Development of this compound, a versatile intermediate for polypropionate synthesis, gave known building blocks for discodermolide

Scalable, Catalytic Asymmetric Synthesis of Syn, Anti Stereotriad Building Blocks for Polypropionate Antibiotics

Asymmetric catalysis and chirality transfer by the 2,3-Wittig rearrangement were combined to provide a syn, anti stereotriad-containing olefinic alcohol in five steps from inexpensive starting materials. Development of this compound, a versatile intermediate for polypropionate synthesis, gave known building blocks for discodermolide

Cleavable Chiral Auxiliaries in 8π (8π, 6π) Electrocyclizations

Low to moderate diastereoselectivity was observed in the 8π electrocyclization of a series of chiral auxiliary-bearing tetraenic esters. In the 8-arylmenthyl series, diastereomeric products were separated by chromatography

A Synthesis of l-Vancosamine Derivatives from Non-Carbohydrate Precursors by a Short Sequence Based on the Marshall, McDonald, and Du Bois Reactions

The carbamate-protected l-vancosamine glycal, viewed as a universal precursor for vancosamine derivatives, was prepared by a short scheme based on diastereoselective addition of an allenyl stannane to a lactaldehyde ether, the tungsten-catalyzed alkynol cycloisomerization, and the rhodium-catalyzed C−H insertion of a carbamate nitrogen. This sequence is a prototype for a new and efficient strategy for the synthesis of 3-amino sugar derivatives. The key intermediate was elaborated to the silyl ether of N,N-dimethyl vancosamine glycal

Deconstruction−Reconstruction Strategy for Accessing Valuable Polyketides. Preparation of the C15−C24 Stereopentad of Discodermolide

An advanced, known intermediate for discodermolide synthesis was prepared by an efficient sequence from the readily available fermentation product oleandomycin. The scheme makes use of a new method for the direct cleavage of aminoglycosides, a critical double-bond isomerization, and a selective protection of two of three hydroxyl groups in a modified oleandolide. This synthesis illustrates a new strategy, “deconstruction−reconstruction”, for accessing stereochemically complex polyketide building blocks

Enantioselective Synthesis of (−)-Dihydrocodeinone: A Short Formal Synthesis of (−)-Morphine^1,^†

The radical cyclization approach to the morphine alkaloids has been applied in an asymmetric synthesis of (−)-dihydrocodeinone. A chiral cyclohexenol (R-32), from the CBS reduction of the enone, is the source of chirality. The first key step, tandem closure in which stereochemistry is controlled by geometric constraints, (−)-15b → (+)-16, was followed by an unprecedented reductive hydroamination, completing the synthesis of (−)-dihydroisocodeine ((−)-17) in 13 steps from commercially available materials