Johnson orthoester Claisen rearrangement

What is Johnson orthoester Claisen rearrangement?

In 1970, Johnson et al. first reported a highly stereoselective synthesis of γ,δ-unsaturated esters. This synthesis involves the reaction between allylic alcohols and an orthoester in the presence of a trace amount of weak acid, like propionic acid.

Johnson orthoester Claisen rearrangement - general reaction scheme
Johnson orthoester Claisen rearrangement

The reaction is a modification or variant of the Claisen rearrangement and is commonly referred to as the Johnson orthoester Claisen rearrangement. Alternatively, it is also known as the Claisen-Johnson orthoester rearrangement or Johnson orthoester protocol.

The process entails the formation of mixed orthoester from allyl alcohol and the added orthoester, which loses an alcoholic component to form a ketene acetal. The ketene acetal then migrates to unsaturated carbonyl compounds via the Claisen rearrangement with high syn selectivity.

The reaction has been extended by Posner to use sulfonyl orthoester and has been applied to the synthesis of a variety of complicated natural products, including squalenes.