Indane-5-sulfonic acid

Indane 36 was added dropwise to excess chlorosulfonic acid (4.5 equivalents) at -10 °C (3 hours) and gave a mixture of the 4- and 5-sulfonyl chlorides 37 and 38 in 76% yield (Equation 12). It was discovered that with increasing temperature the relative amount of indane-5-sulfonic acid increases at the expense of the 4-isomer. This is presumably because the 5-sulfonic acid is relatively less sterically hindered than the 4-acid and consequently is the more thermodynamically stable isomer. 

Additional modifications to the Hantzsch 1,4-dihydropyridine synthesis generally involve the use of activated methylene compounds such as 1,3-diketones, co-cyanoacetophenone, co-phenylacetophenone, a, P-unsaturated ketones, and indane-l,3-diones. A number of efforts to improve reaction yields using eatalysts have also been reported, including the use of hydrotalcite materials, triphenylphosphine copper II triflate, and covalently anchored sulfonic acid on silica gel. Dihydropyridine synthesis has also recently been studied with high success using microwave and solvent-free" reaction conditions. 

The critical point connected with the use of LAS-sulfonic acid is represented by its tendency to undergo color increase dnring storage [12] and this sensitivity may depend on factors such as the LAB quality (i.e., iron, heavy alkylate, and DAT/indane content) as well as operating conditions adopted for its prodnction (i.e., SO3/LAB mole ratio, aging time, temperature, and hydrolysis conditions). Storage of the L AS-snlfonic acid should be preferably made in stainless steel tanks or carbon steel containers lined with epoxy resins and kept at a temperature not exceeding 30°C. 

The utility of the RBR in the synthesis of crovrded trisubstituted alkenes is demonstrated by the synthesis of ampelopsin D (Scheme 8.201. The thioether 48 was generated by acid-promoted cyclization of alcohol 46 and attack by thiol 47 on the benzylic cation. This conpound had a trans-relationship between the aryl branches on the indane system and was produced as a 1 1 mixture of epimers at the thioether linkage. In preparation for the RBR, the thioether 48 was oxidized to sulfone 49, which was treated with base and carbon tetrachloride to produce the RBR product 50 in 52% yield, along with 15% of its (Z)-isomer. Meyers conditions were found to be optimal for stereoselectivity in the RBR, with other methods producing poorer selectivity and unreliable results. The natural product ampelopsin D (51) was obtained after global deprotection with boron tribromide. 

---