An efficient one-pot protocol for the synthesis of phenyl substituted 3-silatetrahydropyransby Svetlana V. Kirpichenko, Bagrat A. Shainyan

Tetrahedron

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Year
2015
DOI
10.1016/j.tet.2014.12.037
Subject
Organic Chemistry / Biochemistry / Drug Discovery

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An efficient one-pot protocol for the synthesis of phenyl substituted 3silatetrahydropyrans

Svetlana V. Kirpichenko , Dr., Bagrat A. Shainyan , Prof. Dr.

PII: S0040-4020(14)01727-X

DOI: 10.1016/j.tet.2014.12.037

Reference: TET 26258

To appear in: Tetrahedron

Received Date: 9 September 2014

Revised Date: 27 November 2014

Accepted Date: 9 December 2014

Please cite this article as: Kirpichenko SV, Shainyan BA, An efficient one-pot protocol for the synthesis of phenyl substituted 3-silatetrahydropyrans, Tetrahedron (2015), doi: 10.1016/j.tet.2014.12.037.

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Grafical absract ________________________________________________________

An efficient one-pot protocol for the synthesis of phenyl substituted 3-silatetrahydropyrans

Svetlana V. Kirpichenko∗ and Bagrat A. Shainyan

ABSTRACT: A new facile and efficient one-pot procedure for the synthesis of 3-phenyl3-silatetrahydropyrans with an easily functionalized Si–Ph bond was developed. The method is based on the intramolecular cyclization of chloromethyl(3-hydroxypropyl)phenylsilanes using the n-Bu4NBr/i-Pr2NEt combination. As an example of functionalization, the synthesis of the first 3-silatetrahydropyran with an exocyclic RO–Si bond is reported.

Keywords: silaheterocycles; 3-Ph-3-silatetrahydropyrans; intramolecular cyclization; electrophilic cleavage of the Ph–Si bond 1. Introduction

Intramolecular cyclization of α,ω-haloalcohols and α,ω-halothiols has remained one of the most simple and efficient approaches to cyclic ethers and sulfides. The method is also applicable to the synthesis of silaheterocycles containing the Si–CH2–Het motif in the ring.1 Earlier we reported a base-promoted ring closure reaction of chloromethyl(mercaptoalkyl)silanes. For example, the sulfide anion generated from S-protected2–4 thiols with NaH2,3 or LiAlH44 undergoes intramolecular cyclization, giving rise to the corresponding 3-silathiophane5 and 3silathiane2–4 derivatives in good yields (Scheme 1). ∗

Dr. S. V. Kirpichenko, Prof. Dr. B. A. Shainyan

A. E. Favorsky Irkutsk Institute of Chemistry

Siberian Division of Russian Academy of Science 1 Favorsky Street, Irkutsk, 664033 (Russian Federation)

E-mail: svk@irioch.irk.ru

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Scheme 1. Synthetic route to 3-silaheterocycles.

However, in the case of Si,O-heterocycles, this procedure can be used only for the synthesis of 3,3-dimethyl-3-tetrahydrofuran (E=O, R1=R2=Me, n=1) from chloromethyl(2-hydroxyethyl)dimethylsilane and sodium hydride.6 Hudrlik et al. showed that treatment of chloromethyl(3hydroxypropyl)dimethylsilane with various base/solvent combinations (NaH/THF, NaH/DME,

KH/hexane, KH/THF, NaH/ether) gave exclusively 2-methyl-2-ethyl-2-silatetrahydrofuran. This result may be attributed to the high oxophilicity of silicon which undergoes intramolecular nucleophilic attack by the intermediate oxyanion followed by migration of an organic group from silicon to the α-carbon.7 The expected 3,3-dimethyl-3-silatetrahydropyran was prepared by using n-BuLi/THF system in a yield as low as 3%. All attempts to synthesize the corresponding

PhSi-substituted heterocycles failed.7

An efficient method to prepare 3,3-dimethyl-3-silatetrahydropyran and its 6-alkyl derivatives was first described by Fessenden et al. in 1964.8 In the slightly modified procedure, these compounds were also obtained in 50–80% yield by heating the corresponding chloromethyl(3hydroxyalkyl)dimethylsilanes with Na2CO3 at high temperatures (>200 oC).9

Later on, some new methods based on using (hydroxymethyl)alkenylsilanes as starting compounds were developed. Thus, Yoshida et al. described the electrophile-induced route to 3,5dimethyl-3-phenyl-3-silatetrahydrofuran, whose formation is dictated by the ability of silyl groups to stabilize a neighboring β-carbocation determining the regioselectivity of the electrophilic addition in the first step.10 Later on, the procedure was modified that resulted in an increased yield of the final product.11

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Scheme 2. Synthesis of 3-silaheterocycles from (hydroxymethyl)alkenylsilanes.

Recently, Tacke et al. reported the first Al(OTf)3-catalyzed intramolecular electrophilic cyclization of (hydroxymethyl)alkenylmethylphenylsilanes to afford the Ph–Si-containing oxasilacycloalkanes in low yield (Scheme 3).11 Note the different regioselectivity of cyclization for R = H and Me, reflecting different polarization of the SiCH2CH=CH2 and SiCH2CH=CMe2 groups.

Scheme 3. Electrophilic cyclization of (hydroxymethyl)alkenylmethylphenylsilanes.

Most of the above protocols suffer from tedious procedures, narrow substrate scopes and/or low efficiency. For these reasons, the development of new reliable and efficient methods for the synthesis of 3-silatetrahydropyrans, especially with a Ph–Si group, is still a challenging task in synthetic organosilicon chemistry. A special emphasis on the Ar–Si compounds is made because they are valuable and versatile intermediates of great synthetic potential. Their advantages are, on the one hand, stability to air and moisture, which allows an easy handling in the synthesis and column purification steps. On the other hand, the high reactivity of the Ar–Si bond to electrophiles opens the way to a wide variety of silaheterocycles with a labile X–Si bond (X = H,

Hal, HO, RO) such as silacyclohexanes,12–15 disilacyclohexanes,12 1,3-silapiperidine16 and 1,4silapiperidines.17–20 With our continuing interest in the chemistry and conformational properties of organosilicon heterocycles, we reported previously the preparation of Si-functionalized silacyclohexane and 3-silathianes via the Ph–Si bond cleavage.15 Here we describe a new efficient protocol for the synthesis of phenyl substituted 3-silatetrahydropyrans 2a and 2b and the use of 2a for the preparation of the first Si,O heterocyle 4a with a labile RO–Si bond.