Enantioselective Synthesis of Spiropyrazolone-Fused Cyclopenta[c]chromen-4-ones Bearing Five Contiguous Stereocenters via (3+2) Cycloaddition

Abstract

An enantioselective synthesis of spiropyrazolone-fused cyclopenta[c]chromen-4-ones is demonstrated via a (3+2) cycloaddition reaction. The reactions of 3-homoacylcoumarins and α,β-unsaturated pyrazolones in the presence of the cinchonaalkaloid derived hydrogen-bonding catalyst provide aforementioned spiropyrazolone-chromenone adducts bearing five contiguous stereocenters, of which one is the spiro all-carbon quaternary stereocenter in high yields (up to 98%) with good to excellent stereoselectivities (>25:1 dr and up to 99% ee). This one-pot methodology could also be practically demonstrated on a gram-scale with similar efficacy.

Recent advances in the applications of pyrazolone derivatives in enantioselective synthesis

“…In 2021, the Lin group reported reactions between 3-homoacylcoumarins 127 and α,β-unsaturated pyrazolones 3aa to forge spiropyrazolone-fused cyclopenta[ c ]chromen-4-ones 128 in the presence of the thiourea C24 as the catalyst (Scheme 27). 53 Importantly, the addition of a catalytic amount of benzoic acid improved the yields and enantioselectivities of the products 128 . The authors proposed that this process was (3 + 2) cycloaddition rather than a traditional Michael/Michael addition sequence.…”

Catalytic Stereoselective Multicomponent Reactions for the Synthesis of Spiro Derivatives: Recent Progress

“…Based on control experiments, a proposed stereochemical model for the [3 + 2]cycloaddition reaction of α,β-unsaturated pyrazolone and 3homoacylcoumarin shown in Scheme 27. [119] Swamy and his group developed a [4 + 2]-spiro-annulation reaction of δ-acetoxy allenoate and alkylbenzoisothiazole dioxide promoted by DABCO (Cat.22) in combination with acetic acid to form the single diastereomer 36. On the other hand, benzannulation catalyzed by DMAP (Cat.23) leads to mterayls 37 by sequential Mannich coupling, hydrogen transfer and cleavage of the CÀ N bond.…”

“…A broad substrate range was established with various α , β ‐unsaturated pyrazolones and 3‐homoacylcoumarin independent of the electronic nature of the substrate (86–99 % yield, dr >25 : 1 and ee up to 98 % ). Based on control experiments, a proposed stereochemical model for the [3+2]‐cycloaddition reaction of α, β ‐unsaturated pyrazolone and 3‐homoacylcoumarin shown in Scheme 27 [119] …”

“…[94][95][96][97][98][99][100][101][102][103][104][105][106][107][108][109][110][111][112][113] This first section is organized by the type of Michael cascade cyclization reactions, i. e., Michael spiro-cyclization, [94][95][96][97][98] Michael/N-hemiketalization or alkylation reaction, [99][100][101][102][103] Michael-Michael aldol reaction, [104][105][106][107] double Michael addition cyclization reaction, [108][109][110] and oxa/aza Michael cascade reaction. [111][112][113] The second part of this review is devoted to stereoselective multicomponent cycloaddition reactions, [114][115][116][117][118][119][120]…”

“…This first section is organized by the type of Michael cascade cyclization reactions, i. e., Michael spiro‐cyclization, [94–98] Michael/ N ‐hemiketalization or alkylation reaction, [99–103] Michael–Michael aldol reaction, [104–107] double Michael addition cyclization reaction, [108–110] and oxa/aza Michael cascade reaction [111–113] . The second part of this review is devoted to stereoselective multicomponent cycloaddition reactions, [114–121] and the third section contains diastereoselective approaches [122–135] and some miscellaneous reactions [136–140] to form spiro‐hetero/carbocycles.…”