In this work we develop practical chemistry for the preparation of N-tert-butyldimethylsilylhydrazone (TBSH) derivatives from carbonyl-containing compounds and show that these products serve as superior alternatives to simple hydrazones in Wolff−Kishner-type reduction reactions, in the Barton vinyl iodide preparation, in the synthesis of vinyl bromides, and in the synthesis of gem-diiodides, gem-dibromides, and gem-dichlorides. In our new procedure for silyl hydrazone synthesis, aliphatic and aromatic ketones and aldehydes are shown to undergo highly efficient coupling (typically >95% yield) to form the corresponding TBSH derivatives when combined with equimolar amounts of 1,2-bis(tert-butyldimethylsilyl)hydrazine (BTBSH) and a catalytic quantity of scandium trifluoromethanesulfonate (typically, 0.01 mol %), neat, or in solvent. Optimized procedures are provided for the use of TBSH derivatives in a Wolff−Kishner-type reduction protocol that proceeds at low temperature (23−100 °C) and in a single reaction ...

https://faculty.chemistry.harvard.edu/files/myers/files/108_2004_furrow_jacs_126_5436.pdf

Practical procedures for the preparation of N-tert-butyldimethylsilylhydrazones and their use in modified Wolff-Kishner reductions and in the synthesis of vinyl halides and gem-dihalides.

A facile and practical methodology for the synthesis of synthetically useful diarylmethanol-based 1,4-diols and enantiomerically pure BINOL-derived diols with axial and sp(3)-central chirality has been developed through neighboring lithium-promoted [1,2]-Wittig rearrangement. The chirality transfer process shows a broad substrate scope in terms of the aromatic ether substituent, which allows access to a broad of range of chiral 1,1'-binaphthalene-2-α-arylmethanol-2'-ols with excellent enantioselectivities (>99 % enantiomeric excess) and yields (84-96 %). This should be considered as an available and attractive chiral source to design and prepare privileged ligands or catalysts.

Neighboring Lithium‐Assisted [1,2]‐Wittig Rearrangement: Practical Access to Diarylmethanol‐Based 1,4‐Diols and Optically Active BINOL Derivatives with Axial and sp3‐Central Chirality

n-Butyllithium/N,N,N‘,N‘-tetramethylethylenediamine-mediated ortholithiations of aryloxazolines are described. Methyl substituents on the aryloxazoline and substituents at the meta position of the arenes (methoxy, oxazolinyl, and fluoro) influence the rates and the mechanisms. Monomer- and dimer-based reactions are implicated. Density functional calculations probe details of the mechanism and suggest the origins of cooperative effects in meta-substituted aryl oxazolines.

n-Butyllithium/N,N,N',N'-tetramethylethylenediamine-mediated ortholithiations of aryl oxazolines: substrate-dependent mechanisms.

The benzannulation reactions of substituted 3-alkoxycarbonyl-3,5-hexadienoic and 3-alkoxycarbonylhex-3-en-5-ynoic acids offer a straightforward access to various polysubstituted aromatic compounds. The process is very flexible, and can be applied to the regiospecific preparation of oligoaryls, naphthalenes, ring-fused heterocycles, chiral tetrahydronaphthalenes, C-aryl-glycosides and many natural products of different structure. In this Concept article, we highlight the potential of this annulation reaction by illustration of our recent contribution to this field, as well as the studies previous reported by others.

Recent Advances in the Benzannulation of Substituted 3‐Alkoxycarbonyl‐3,5‐hexadienoic Acids and 3‐Alkoxycarbonylhex‐3‐en‐5‐ynoic Acids to Polysubstituted Aromatics

This report describes the preparation of a series of 17 novel racemic spirocyclic scaffolds that are intended for the creation of compound libraries by parallel synthesis for biological screening. Each scaffold features two points of orthogonal diversification. The scaffolds are related to each other in four ways: (1) through stepwise changes in the size of the nitrogen-bearing ring; (2) through the oxidation state of the carbon-centered point of diversification; (3) through the relative stereochemical orientation of the two diversification sites in those members that are stereogenic; and (4) through the provision of both saturated and unsaturated versions of the furan ring in the scaffold series derived from 3-piperidone. The scaffolds provide incremental changes in the relative orientation of the diversity components that would be introduced onto them. The scaffolds feature high sp(3) carbon content which is essential for the three-dimensional exploration of chemical space. This characteristic is particularly evident in those members of this family that bear two stereocenters, i.e., the two series derived from 3-piperidone and 3-pyrrolidinone. In the series derived from 3-piperidone we were able to "split the difference" between the two diastereomers by preparation of their corresponding unsaturated version.

/pdf/synthesis-of-a-family-of-spirocyclic-scaffolds-building-3nlkds54d2.pdf

Synthesis of a Family of Spirocyclic Scaffolds; Building Blocks for the Exploration of Chemical Space

The lithiation of (29) and (30) is shown to occur at all three sites with a dissimilar kinetic preference. For the dihydrofuran, reaction at the proton labeled H β' operates predominantly; in the dihydropyran example, H α is the favored site of deprotonation. These protons repre- sent those that are the most deshielded in the respective 1 H NMR spec- tra. The same is true for (9) and (19), both of which undergo mediation adjacent to the ring oxygen. No crossover in regioselectivity is obser- ved, presumably because the methoxy substituent is sterically precluded from rotating freely. Mixed complexes (dimers, etc.) or mixed aggregates in low equilibrium concentration are key to understanding the acidifi- cation phenomenon of ortho hydrogens. As a consequence of the dominance of regiocontrol by the ring oxygen in (9), a convenient means has been developed for elaboration of the tricyclic eastern sector of the austa- lide mycotoxins

Relevance of Conformational Constraints to the Regioselective Lithiation of Aromatic Diethers. Application to the Convenient Construction of the DEF Tricyclic Subunit of the Austalides

Alkoxy and cyclic ether oxygens exhibit disparate capabilities for directing ortho lithiation

Furo[3,4-g]-1-benzopyrane derivative (19), representing the DEF subunit common to all known austalide mycotoxins, has been economically synthesized from 2,3-dihydropyran in 8 steps via several highly stereo- and regioselective transformations

A unified synthetic strategy for elaboration of the DEF tricyclic subunit common to the austalide mycotoxins

A Unified Synthetic Strategy for Elaboration of the DEF Tricyclic Subunit Common to the Austalide Mycotoxins.

Relevance of Conformational Constraints to the Regioselective Lithiation of Aromatic Diethers. Application to the Convenient Construction of the DEF Tricyclic Subunit of the Austalides.

Matthias M. Schulze

Papers

Relevance of Conformational Constraints to the Regioselective Lithiation of Aromatic Diethers. Application to the Convenient Construction of the DEF Tricyclic Subunit of the Austalides

Alkoxy and cyclic ether oxygens exhibit disparate capabilities for directing ortho lithiation

A unified synthetic strategy for elaboration of the DEF tricyclic subunit common to the austalide mycotoxins

A Unified Synthetic Strategy for Elaboration of the DEF Tricyclic Subunit Common to the Austalide Mycotoxins.

Relevance of Conformational Constraints to the Regioselective Lithiation of Aromatic Diethers. Application to the Convenient Construction of the DEF Tricyclic Subunit of the Austalides.