Fun With Unusual Functional Groups: Sulfamates, Phosphoramidates, and Di-tert-butyl Silanols

Abstract

Compared to ubiquitous functional groups such as alcohols, carboxylic acids, amines, and amides, which serve as central "actors" in most organic reactions, sulfamates, phosphoramidates, and di-tert-butyl silanols have historically been viewed as "extras". Largely considered functional group curiosities rather than launch-points of vital reactivity, the chemistry of these moieties is under-developed. Our research program has uncovered new facets of reactivity of each of these functional groups, and we are optimistic that the chemistry of these fascinating molecules can be developed into truly general transformations, useful for chemists across multiple disciplines. In the ensuing sections, I will describe our efforts to develop new reactions with these "unusual" functional groups, namely sulfamates, phosphoramidates, and di-tert-butyl silanols.

Keywords: alkene functionalization; aza-Wacker; organic methodology; silanol; total synthesis.

Scheme 1.

Classical and tethered aza-Wacker cyclization reactions at the time of our laboratory’s entry into the field.

Scheme 2.

Sulfamate-tethered aza-Wacker cyclization reactions give alkenyl oxathiazinane products, which are allylic amine surrogates.

Scheme 3.

Our progress towards bactobolin A.

Scheme 4.

Application of our sulfamate-tethered aza-Wacker cyclization to the preparation of orthogonally protected D-galactosamines.

Scheme 5.

Application of our sulfamate-tethered aza-Wacker cyclization to the preparation of a kasugamine synthon.

Scheme 6.

An unusual 5-chloro-8-hydroxyquinoline arm allows for complete diastereocontrol in our phosphoramidate tethered aza-Wacker cyclization.

Scheme 7.

Conversion of cyclic phosphoramidates into (A) 1,3-chloroamines and (B) 1,3-aminoalcohols.

Scheme 8.

(A) Synthesis and (B) ring-opening of sulfamate epoxide substrates.

Scheme 9.

(A) Ring-opening of aziridines by pendant sulfamates. (B) Functionalization reactions of the products.

Scheme 10.

Synthesis of alkenyl silanols.

Scheme 11.

A remarkable cascade, likely triggered by adventitious TfOH.

Scheme 12.

1 equivalent of NaHCO₃ stabilizes the dioxasilinane product.

Scheme 13.

Formal rearrangement of allylic silanols.

Scheme 14.

Dioxasilolanes and organomercury ketones from allylic silanols.

Scheme 15.

A tethered silanoxy-iodination reaction.

Scheme 16.

Silanoxyselenylation and hydroxyselenylation reactions.

Scheme 17.

Cleavage of epoxides with silanol tethers.

Scheme 18.

“Dancing” silanols.

Scheme 19.

A short preparation of muricatacin.

Scheme 20.

Ring opening of aziridines by pendant silanols allows for the preparation of sphingosine-type natural products.

Scheme 21.

Stereospecific preparation of 1’-amino-tetrahydrofurans.

Scheme 22.

Interception of palladium pi-allyl species by pendant silanols.