Sulfur as a regiochemical control element. Cycloadditions of 2-alkoxy(acyloxy)-3-alkyl(aryl)thiobuta-1,3-dienes

Abstract

The cycloadditions of 2-methoxy-3-phenylthiobuta-1,3-diene, the 4'-chlorophenylthio and 2'-pyrimidylthio derivatives, and 2-acetoxy-3-phenylthiobuta-1,3-diene and its 4'-methoxyphenylthio derivative with unsymmetrical dienophiles are examined. The effect of silica gel, boron trifluoride etherate, and magnesium bromide on the regiochemistry is probed. In situ generation of the diene from the precursor cyclobutene and cycloaddition is a promising technique for sluggish dienophiles such as cyclohex-2-en-1-one. The use of a cisoid diene, 2,3-dimethylene-l,4-oxathiin, has also been examined. By variation of the substituents and use of thermal vs. Lewis acid catalysis, either sulfur or oxygen dominance of regiochemistry is possible. The former, combined with desulfurization, offers an approach to 1,3-substituted cyclohexanes via cycloaddition chemistry-a type of substitution not available in the normal Diels-Alder reaction. Thus, sulfur serves as a regiochemical control element. Rationalization of these results in terms of current concepts is presented. The frontier-orbital approach modified by consideration of charge-transfer (polar) interactions best accounts for the results. The site of complexation of the Lewis acids in these reactions also appears open to question.

2-Methoxy-3-phenylthio-1,3-butadiene

“…2 The Diels-Alder regiochemistry is usually controlled by the sulfur (eq 3), but the competition between dominance by the sulfur or oxygen depends on the substitution on the heteroatoms, the presence of Lewis acids, and the choice of dienophile. 2-Alkoxy(acyloxy)-3-arylthiobuta-1,3-dienes such as (2) are highly reactive and versatile in Diels-Alder reactions.…”

Highly Regioselective and Stereoselective Hydrostannylation of (Z)-2-Ethoxycarbonyl-1,3-Enynes Leading to (1E,3E)-2-Ethoxycarbonyl-3-Stannyl-1,3-Dienes

“…[13][14][15][16][17][18] In addition, difunctionalised 1,3-dienes containing heteroatoms can control both regioselectivity and stereoselectivity and play a key role in cycloadditions. [19][20][21][22] Jin and co-workers described the stereoselective synthesis of 2-alkoxy-3-alkyl(aryl)thiobuta-1,3-dienes by a Negishi coupling reaction between α-alkyl(aryl)thio vinyl zinc chlorides and α-bromo vinyl ethers. 23 Coleman and Walczak reported 24 the stereoselective synthesis of (E,E)-1-tributylstannyl-4-borylbuta-1,3-diene and its use as an orthogonal Stille and Suzuki-Miyaura coupling partner.…”

Pattern recognition analysis in complex molecule synthesis and the preparation of iso-Diels–Alder motifs

“…In each case, removal of the temporary moiety (-TMS or -SPh) occurred with migration of the olefin to give rise to IDA(o) adducts. Other studies worth noting in this regard, which dealt with competing diene directivities in the DA reaction, include the historic work of Trost et al (27,28) and Cohen and coworkers (29).…”