Strategies for the Preparation of Differentially Protected ortho-Prenylated Phenols

Abstract

A new process for ortho-prenylation of phenols is presented within the context of known methods. All of the processes are briefly assessed with regards to the substitution patterns and accompanying functional groups tolerated by each strategy. The conclusion reached is that a new procedure using ortho-quinone methides, for which an experimental protocol is provided, offers the greatest generality and flexibility in the preparation of ortho-prenylated phenol derivatives.

Figure 1

All of the analogs of differentially protected ortho-prenylated dihydroxyphenol nuclei (PH).

Figure 2

Differentially protected dihydroxyphenols that are commercially available.

Scheme 1

The general DoM strategy

Scheme 1a

Scheme 1b

Scheme 1c

Scheme 1d

Scheme 2

General metal exchange strategies for prenylation

Scheme 2a

Scheme 2b

Scheme 2c

Scheme 2d

Scheme 2e

Scheme 3

General phenoxide C-prenylation strategy

Scheme 3a

Scheme 3b

Scheme 4

The general Claisen rearrangement strategy

Scheme 4a

Scheme 4b

Scheme 5

General Friedel–Crafts prenylation strategy

Scheme 5a

Scheme 5b

Scheme 5c

Scheme 5d

Scheme 5e

Scheme 6

General Birch reductions strategy

Scheme 6a

Scheme 7

1,4-Conjugate addition strategy

Scheme 7a

Scheme 8

General benzylic coupling strategy

Scheme 8a

Scheme 8b