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. 2022 Aug 26;13(38):11427-11432.
doi: 10.1039/d2sc02827a. eCollection 2022 Oct 5.

A base-catalyzed approach for the anti-Markovnikov hydration of styrene derivatives

Spencer P Pajk  1 , Zisong Qi  1 , Stephen J Sujansky  1 , Jeffrey S Bandar  1
Affiliations

A base-catalyzed approach for the anti-Markovnikov hydration of styrene derivatives

Spencer P Pajk et al. Chem Sci. .

Abstract

The base-catalyzed addition of 1-cyclopropylethanol to styrene derivatives with an acidic reaction workup enables anti-Markovnikov hydration. The use of either catalytic organic superbase or crown ether-ligated inorganic base permits hydration of a wide variety of styrene derivatives, including electron-deficient, ortho-substituted and heteroaryl variants. This protocol complements alternative routes to terminal alcohols that rely on stoichiometric reduction and oxidation processes. The utility of this method is demonstrated through multigram scale reactions and its use in a two-step hydration/cyclization process of ortho-halogenated styrenes to prepare 2,3-dihydrobenzofuran derivatives.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Fig. 1
Fig. 1. Examples of the importance of β-aryl substituted alcohols.
Fig. 2
Fig. 2. Overview of a base-catalyzed approach to anti-Markovnikov styrene hydration.
Scheme 1
Scheme 1. Optimization studies for (a) superbase-catalyzed alcohol addition and (b) ether hydrolysis. a Yields determined by 1H NMR spectroscopy. b Isolated yield of purified product.
Scheme 2
Scheme 2. Comparison of base-catalyzed hydration to hydroboration/oxidation methods. a Yields and regioselectivities determined by 1H NMR spectroscopy of the crude reaction mixture; yields from Table 1 represent isolated yields. b Yields are of purified alcohol product. c 5 equiv. of 4 used.
Scheme 3
Scheme 3. Examples of preparative scale anti-Markovnikov hydration reactions; yields are of isolated alcohol product.
Scheme 4
Scheme 4. Utility of Table 1 alcohol products for dihydrobenzofuran derivative synthesis; yields are of isolated product from the cyclization step using given conditions. a CuI (10 mol%), 8-quinolinol (15 mol%), Cs2CO3 (1.5 equiv.), PhMe, 110 °C, 16 h. b NaH (1.5 equiv.), THF, 70 °C, 16 h. c Pd(OAc)2 (3 mol%), JohnPhos (4 mol%), Cs2CO3 (1.5 equiv.), PhMe, 80 °C, 22 h.
See this image and copyright information in PMC

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