Synthesis of acetal protected building blocks using flow chemistry with flow I.R. analysis: preparation of butane-2,3-diacetal tartrates

Abstract

The syntheses of butane-2,3-diacetal protected tartrate derivatives are described using continuous flow processing techniques with in-line purification and I.R. analytical protocols.

The integration of flow reactors into synthetic organic chemistry

“…We have used such a system to help evolve a flow route to various butane‐2,3‐diacetals (BDAs) which are key building block in many natural product syntheses. The flow approach allowed the BDA units to be prepared generally in higher yields and with higher reproducibility than the corresponding batch processes . For example, the BDA protected tartrate was obtained from a mixed stream of dimethyl‐ l ‐tartrate and trimethyl orthoformate and a stream containing butane‐2,3‐dione together with catalytic quantities of camphorsulfonic acid (CSA).…”

“…In a final sequence a BDA protected glycolate, another useful building block, was synthesized using related procedures (Scheme ) . Applying similar conditions to those used for the tartrate protection reaction above, enantiomericly pure chloropropanediol was converted to the bis ‐acetal in 95% yield without racemization.…”

Continuous‐flow syntheses of heterocycles

“…To ease the in situ reaction monitoring, a flow IR equipment was connected to the outgoing reaction stream [47].…”

Stereoselective reactions of a thioester butanediacetal with various electrophiles

“…[4][5][6][7] The key derivatives of butanediacetals can be assembled using flow chemistry methods. 8,9 Butanediacetals with a rigid chair conformation induce excellent diastereoselectivity in many types of reactions, including alkylations with alkyl halides, aldol reactions with aldehydes, addition of zinc alkynylides or Grignard reagents to butanediacetals derivatives with an aldehyde group, or radical alkylations. [10][11][12][13][14][15] In the butanediacetals obtained from dimethyl tartrate, the ester groups were replaced with thioesters to give compound 1 (Fig.…”