Organocatalytic stereocontrolled synthesis of 3,3′-pyrrolidinyl spirooxindoles by [3+2] annulation of isocyanoesters with methyleneindolinones

Abstract

A stereoselective [3+2] cycloaddition of isocyanoesters to methyleneindolinones catalyzed by a quinine-based thiourea-tertiary amine has been successfully developed. Just by tuning the protecting groups on substrates, a variety of optically enriched 3,3'-pyrrolidinyl spirooxindole diastereomers could be obtained in excellent enantioselectivities (up to 99% ee).

Catalytic Isonitrile Insertions and Condensations Initiated by RNC–X Complexation

“…(37)]. [70] By varying the protecting group on the methyleneindolinone, the syn - or anti -spiroindole is generated with moderate to good diastereoselectivity and with high enantioselectivity. N -Phenylamide-protected indolinones give anti -spirooxindoles in which the two ester substituents lie on opposite sides of the indoline ring.…”

Catalytic Enantioselective Michael Addition of α‐Aryl‐α‐Isocyanoacetates to Vinyl Selenone: Synthesis of α,α‐Disubstituted α‐Amino Acids and (+)‐ and (−)‐Trigonoliimine A

“…The results (for details, see the Supporting Information) allowed us to draw the following conclusions: a) The reaction is best carried out in a nonpolar aprotic solvent in the presence of 4 molecular sieves; [6][7][8] b) The alkyl residue of the ester impacted the ee value of the reaction with the following trend being clearly observable: methyl ester > ethyl ester > tert-butyl ester; c) The presence of an hydrogen-bond donor function at C6' of the cinchona alkaloids is essential and quinine derivatives having an OH at C6' displayed better enantiodiscriminating power than those bearing amido and thioureido groups at 6'. [18] However, b-ICD and its derivatives were ineffective; [19] d) The alkyl residue introduced to the C9 OH group of quinine also influenced the ee value of the reaction with an nBu group being optimal.…”

“…[2] The enantioselectivity of this reaction was, however, moderate (< 39 % ee). In contrast, a number of Lewis-acid-and small-organomolecule-catalyzed enantioselective [2+3] cycloadditions of a-isocyanoacetates with aldehydes, [3] imines, [4] azodicarboxylates, [5] and polarized carboncarbon double bonds, such as nitroalkenes, [6] a,b-unsaturated ketones, [7] and maleimides, [8] have been developed to access enantioenriched five-membered heterocycles. In contrast, catalytic enantioselective Michael addition of a-isocyanoacetates was met with only limited success.…”

Enantioselective Synthesis of Quaternary Δ4‐ and Δ5‐Dehydroprolines Based on a Two‐Step Formal [3+2] Cycloaddition of α‐Aryl and α‐Alkyl Isocyano(thio)acetates with Vinyl Ketones

“…[2] Onem ajor thoroughly investigated convergent approacht ot he enantioselective synthesis of these heterocyclic systems relies on the catalytic [3+ +2] cycloadditionr eaction between azomethine ylides and electron-deficient olefins (Scheme 1a,l eft). [4] Most studies on catalytic enantioselective cycloadditionso faisocyanoacetates involve very reactive olefins, such as maleimides, [5] nitroalkenes, [6] b,g-unsaturated a-keto esters, [7] methyleneindolinones [8] and allenoates, [9] and require, with af ew exceptions, [6,8] combinedm etal/Brønsted base catalysis. [4] Most studies on catalytic enantioselective cycloadditionso faisocyanoacetates involve very reactive olefins, such as maleimides, [5] nitroalkenes, [6] b,g-unsaturated a-keto esters, [7] methyleneindolinones [8] and allenoates, [9] and require, with af ew exceptions, [6,8] combinedm etal/Brønsted base catalysis.…”