Studies with trialkylsilyltriflates: new syntheses and applications

One element of structure that invariably increases the difficulty of a chemical synthesis is the presence in the target molecule of contiguous all-carbon quaternary stereocenters. This Perspective will examine the most useful transformations and strategies devised recently for directly assembling this structural unit.

https://www.pnas.org/content/pnas/101/33/11943.full.pdf

Contiguous stereogenic quaternary carbons: A daunting challenge in natural products synthesis

The preparatively important catalytic opening of epoxides to β-titanoxy radicals via single-electron transfer (SET) is described. These radicals can be reduced to alcohols or participate in C−C bond-forming reactions. A key step in the catalytic cycle is the conceptually novel protonation of titanium−oxygen and −carbon bonds. Our method combines the advantages of radical reactions, e.g., high functional group tolerance and stability of radicals under protic conditions, with the ability of organometallic complexes to determine the course of transformations in reagent-controlled reactions.

Emergence of a Novel Catalytic Radical Reaction: Titanocene-Catalyzed Reductive Opening of Epoxides

Although there are many reagent combinations that can initiate polyene cyclizations, simple electrophilic halogen sources have not yet proven broadly effective as promoters of such processes. Herein is described a readily prepared and stable class of reagents capable of effecting such transformations for a wide range of electron-rich and -deficient terpenes derived from geraniol, farnesol, and nerol, thereby enabling the effective synthesis of a diverse array of complex chlorine-, bromine-, and iodine-containing polycyclic frameworks. Efforts to date have led to the first racemic laboratory total synthesis and structural revision of the anti-HIV natural product peyssonol A as well as an efficient and concise inaugural total synthesis of peyssonoic acid A. They have also permitted formal racemic total syntheses of aplysin-20, loliolide, K-76, and stemodin to be achieved through routes that are typically shorter, higher-yielding, and more environmentally conscious than previous efforts. Preliminary attempts to use chiral forms of the reagent class for enantioselective alkene halogenation are also described.

Simple Reagents for Direct Halonium-Induced Polyene Cyclizations

Carbonyl compounds undergo α-alkylation via the corresponding silyl enol ethers using SN1 active alkyl halides or acetates in the presence of Lewis acids. This methodology extends the scope of carbonyl chemistry considerably, since SN1 active alkylating agents are generally base sensitive and therefore unsuitable for reactions with enolate anions or nitrogen analogs. A prime example is the α-tert-alkylation of aldehydes, ketones and esters.

Jagabandhu Das

Papers

Total synthesis of (.+-.)-aphidicolin

Total synthesis of the complement inhibitor K-76 in racemic form. Structural assignment to "K-76 monocarboxylic acid"

Total synthesis of (.+-.)-stemodin and (.+-.)-stemodinone

Total synthesis of the complement inhibitor K-76 in racemic form. Structural assignment to "K-76 monocarboxylic acid"

A new method for stereospecific cis hydroxylation of olefins