2.3- dihydro-l,4-benzoxathiins

The cis-2,3-diaryl-2,3-dihydro-l,4-benzoxathiin is a very unique structural motif. Other than scattered reports in the literature on the formation of this scaffold, there was no effective asymmetric synthesis for it [6]. We explored two major synthetic approaches to realize the key chiral as-diaryl dihydrobenzoxathiin scaffold, as shown in Scheme 5.3. One was the quinone ketal route in which the quinone ketal 13 and the chiral mercaptol alcohol 14 were the key intermediates. The other approach was the stereo- and enantioselective reduction of the diaryl benzoxathiin 16. The key mercaptol alcohol 14 and the diaryl benzoxathiin 16 were both envisioned to be prepared from the key, common iodoketone intermediate 15. 

The chiral 2,3-dihydro-l,4-benzoxathiins are useful compounds but there were no effective asymmetric methods to access these compounds in the literature [15, 17,... 

Most partially saturated ring systems, 2,3-dihydro-l,4-dioxin 10 (sometimes named as 1,4-dioxene), 2,3-dihydro-1,4-dithiin 11, 2,3-dihydro-l,4-oxathiin 12, 2,3-dihydro-l,4-benzodioxin or 1,4-benzodioxane 13, 2,3-dihydro-l,4-benzodithiin 14, and 2,3-dihydro-l,4-benzoxathiin 15 are well investigated. Ring numbering for compounds 10-12 is followed as shown, independently of the presence of substituents. 

Chiral iy -2,3-disubstituted 2,3-dihydro-l,4-benzoxathiins 73 are available from the reaction of enantio-enriched mercaptoethanols with quinone ketals. An initial Michael addition is followed by cyclisation and aromatisation <04TL5429>. 

FIGURE 14.1 The stractures of glutathione and its conjugate, Af-acetylcysteine and its conj ugate, (25,3ff)-3-(4-hydroxyphenyl)-2-[4-(2-piperidin-1 -ylethoxy)phenyl]-2,3-dihy-dro-l,4-benzoxathiin-6-ol (A) and its bis-cyano adduct (B), (25,3/f)-(-I-)-3-(3-hydro-xyphenyl)-2-[4-(2-pyrrolidin-l-ylethoxy)-phenyl]-2,3-dihydro-l,4-benzoxathiin-6-ol (C) and its JV-acetylcysteine adduct (D), dansyl glutathione, /f-(-t )-pulegone, menadione, and iodoacetamide. 

Derivatives of 2,3-dihydro-l,4-oxathiin and 1,4-benzoxathiins have been patented as agrochemicals. An important development in fungicidal research has been the discovery of so-called systemic fungicides. Unlike surface fungicides which may require repeated... 

Benzoxathiins 265 can be prepared by rearrangement of the 8-(2-bromoethoxy)-2,3-dihydro-2//-l-benzothio-pyran 264 in DMF at 80°C (Equation 41) <2003MI187>. 

Synthesis of 1,4-dihydro-2,3-benzoxathiin 3-oxide as a useful precursor of o-quinodimethane The sultine l,4-dihydro-2,3-benzoxathiin 3-oxide 9 and substituted derivatives are ideal reagents for the in situ synthesis of o-quinodimethanes (o-xylylenes) 170 because they decompose smoothly in refluxing benzene at ca. 80°C and do not... 

Thermal decomposition of l,4-dihydro-2,3-benzoxathiin 3-oxides generates o-xylylenes which can be trapped by methyl 2-acetamidoacrylate yielding tetralin-based a-amino acids <04S558>. A phosphazene base [EtN=P(NMe2)2(N=P(NMe)2)3)] is used to generate the ylide from chiral oxathiane 74 in a two-step asymmetric synthesis of aziridines from tosylimines <04JOC1409>. 

Oxidation of freshly liberated 1,2,3,4-tetrahydrophthalazine (42) by mercury(II) oxide in the presence of sulfur dioxide gave an (unseparated) mixture of 1,4-dihydro-2,3-benzoxathiin 3-oxide (43) and l,3-dihydrobenzo[c]thiophene 2,2-dioxide (44) (substrate, CH2CI2, -20X, S02i, then HgOj, 20°C, 12h 45% of a 9 1 mixture in which the compounds were clearly identified). ... 

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