Highly Regioselective Construction of Spirocycles via Phosphine-Catalyzed [3 + 2]-Cycloaddition

Abstract

A direct entry to spirocycles with low to moderate regioselectivity was achieved by triphenylphosphine-catalyzed [3 + 2]-cycloaddition of active exo-methylenecycles (1) and ethyl 2,3-butadienoate (2). The regioselectivity of the reaction was greatly improved by using the bulky tert-butyl ester of the 2,3-butadienoate (5). The regioselectivity of the reaction was further enhanced by using the tert-butyl 2-butynoate as the substrate. This protocol provided an efficient entry to the skeleton of spirocarbocycles, especially spiro[4.n]alkanes.

Nucleophilic Phosphine Organocatalysis

“…Lu and coworkers also reported a highly regioselective construction of spirocycles via triphenylphosphine-catalyzed [3 þ 2] cycloaddition of a-methylene cyclic ketones with alkynyl and allenyl esters (Scheme 6.6). [65] The bulky tert-butyl 2,3-butadienoate gave marked improvement in regioselectivity over smaller esters, supporting a steric argument for the observed regioselectivity.…”

Studies on the asymmetric, phosphine-promoted [3+2] annulations of allenic esters with 2-aryl-1,1-dicyanoalkenes

“…6 Other classes of electron-deficient olefins were shown to be competent substrates for [3+2] annulations with allenoates, however, asymmetric variants of these reactions have not been reported so far. Examples include annulations on a,b-unsaturated a-aminoacid derivatives 7 and amides, 8 tropone, 9 chromones, 10 and acrylonitrile. 11 In this context, the aim of enlarging the scope of enantioselective cyclizations on allenoates prompted us to investigate the use of chiral phosphines as catalysts for [3+2] annulations on a special class of electron-deficient a,b-unsaturated olefins, that is, arylidene malononitriles.…”

Highly Diastereoselective Synthesis of Bicyclo[3.2.1]octenones through Phosphine‐Mediated Condensations of 1,4‐Dien‐3‐ones

“…[5] Complementary approaches to simple carbocycles from acyclic precursors include phosphine-mediated methods such as [3+2] annulations [6] as well as intramolecular RauhutCurrier, [7] Morita-Baylis-Hillman, [8] and S N 2 reactions.…”

“…Phosphine-promoted reactions of 1,4-dien-3-ones. [6][7][8]. The use of 1 equivalent of pyridine improved the yield to synthetically useful levels while maintaining the high diastereoselectivity (Table 1, entry 8); no reaction was observed when pyridine was used in the absence of phosphine.…”