Validation of Diethoxyphosphonate as an Effective Agent for Charge Transfer in Anion Relay Chemistry (ARC)

Abstract

The diethoxyphosphonate group comprises an effective agent to achieve negative charge migration in Type II Anion Relay Chemistry (ARC). The process involves a [1,4]-phosphorus-Brook rearrangement that proceeds via a phosphacyclic intermediate leading to an anion that can be captured by reactive electrophiles. In the absence of an exogenous electrophile, the anion derived via phosphorus migration undergoes internal displacement of the phosphonate group to produce a diasteriomeric mixture of cyclopropanes.

Synthesis of Vinyl Cyclopropanes via Anion Relay Cyclization

“…Smith and others have demonstrated through-space ARC strategies that have primarily utilized [1,4]-Brook rearrangements and [1,4]-phosphorus-Brook rearrangements for the migration of negative charge (Scheme ). − On the basis of our previous efforts that utilize the retro-Claisen reaction of ketones and esters for the generation of carbanions in situ , we hypothesized that similar retro-Claisen reactions of carbonyl compounds could be used to effect anion relay without the need to synthesize silanes or phosphinates …”

[1,3]/[1,4]-Sulfur atom migration in β-hydroxyalkylphosphine sulfides

“…Other [1,3]-rearrangements of organophosphorus compounds include phosphoenolpyruvate formation from phosphonopyruvate [51], benzylphosphonium salt formation from the corresponding o-methylaryl-substituted precursors [52], or the formation of ketophosphonates from vinylphosphates [53]. [1,4]-Rearrangements include that of o-phosphorus-substituted benzyl carbanions [34], phosphorus group migration in O-phosphorylated 1,4-benzodiazepines [54], or phosphoryl group carbon-to-oxygen transfer [55]. The common feature of every rearrangement presented above is the cleavage of one single bond between phosphorus and either carbon or oxygen atom, while the multiple bond remains intact.…”

Asymmetric Synthesis of Functionalized trans-Cyclopropoxy Building Block for Grazoprevir

“…Results from each of these strategies were unsatisfactory with our substrates, in terms of diastereo- and/or enantioselectivity, yield, and practicality for large-scale production. Instead of focusing on direct cyclopropanation for the preparation of cyclopropanols, we envisioned that a practical and stereospecific preparation of trans -2-substituted cyclopropanols could be realized from readily accessible starting materials 4 and 5a – b , requiring the following two key transformations: (1) asymmetric cyclopropanation by treating chiral epoxides 5a – b with phosphonate 4 through a [1,3]-phosphorus-Brook rearrangement , and (2) stereospecific Baeyer–Villiger oxidation of cyclopropyl ketone 3 , as depicted in Scheme .…”