Spiro Compounds. Группа авторов

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Scheme 3.8 Bimetallic relay catalysis for the enantioselective synthesis of the spirotropanyl oxindole.

      Source: Modified from Jia et al. [18].

Recently, the same group established the asymmetric Diels–Alder reaction/[3,3]sigmatropic rearrangement cascade of methyleneindolinones 1 with 1‐thiocyanatobutadienes 101 for the synthesis of spiranic cyclohexenyl isothiocyanates 102 (Scheme 3.10) [20]. The reaction uses Ni(II) complex and the chiral N,N′‐dioxide ligand 103, providing a range of spiro cyclohexenyl isothiocyanates in high yields (64–97%) with excellent diastereo (>15 : 1 in all the cases) and enantioselectivities (65–94% ee). Mechanistically, the reaction involves the initial activation of methyleneindolinones 1 by the chiral L‐PiPr₂/Ni(II) complex through coordination with the two carbonyl groups, generating intermediate 104. Subsequently, the 1‐thiocyanatobutadienes 101 participates in a stereoselective quasi‐concerted Diels–Alder cycloaddition from the Re face of 104 to afford intermediate 105, which further undergoes a suprafacial [3,3]sigmatropic rearrangement to furnish the final product 102. Interestingly, the authors applied the developed method to the gram‐scale synthesis of NITD609, an antimalarial active spirocyclic indole. Shortly after, the same group also developed a catalytic asymmetric Diels–Alder reaction for the synthesis of optically pure spiro[cyclohexane‐oxindoline] derivatives using Zn(OTf)₂ and a chiral N,N′‐dioxide ligand [21].

Scheme 3.9 Regio‐ and enantioselective aza‐Diels–Alder reactions of 3‐vinylindoles.

      Source: Modified from Zheng et al. [19].

      3.2.3 Organometallic Miscellaneous Strategies to Construct Spiro Compounds

The following reports are based on the construction of strained small ring spirocyclic scaffolds and on the utilization of merged metal‐ and organocatalytic strategies. The first example deals with an enantioselective [2+2] cycloaddition of disubstituted ketenes 114 and isatins 115 for the synthesis of spirocyclic β‐lactones 116, reported by the group of Feng in 2014 (Scheme 3.11) [22]. The method utilizes Sc(OTf)₃ as Lewis acid catalyst in the presence of the chiral N,N′‐dioxide ligand 117, responsible for controlling the stereochemistry of the product 116. A variety of chiral β‐lactones were obtained in excellent yield (80–96%) with very high diastereo‐ and enantioselectivity (>20 : 1 dr and 88–97% ee).

Scheme 3.10 Ni‐catalyzed asymmetric Diels–Alder/[3,3]sigmatropic rearrangement cascade between methyleneindolinones with 1‐thiocyanatobutadienes.

      Source: Modified from Zhou et al. [20].

In 2015, Tanaka and coworkers outlined an enantioselective [2+2+2] cycloaddition approach to construct spiro‐cyclohexadienes 123, starting from terminal alkynes 124, acetylenedicarboxylates 125, and cyclopropylideneacetamides 126 (Scheme 3.12) [23].

Scheme 3.11 Scandium‐catalyzed asymmetric cycloaddition between ketenes and isatins.

      Source: Modified from Hao et al. [22].

Scheme 3.12 Rhodium‐catalyzed [2+2+2] cycloadditions between alkynes and cyclopropylideneacetamides.

      Source: Based on Yoshida et al. [23].

      In the reported reaction mechanism, a rhodium(I)/(S)‐binap cationic complex is responsible for the excellent stereocontrol (96%–>99% ee), affording the spiro cyclohexadiene products 123 in moderate to good yield (31–76%). Mechanistically, the reaction proceeds through the formation of intermediate 127 by coupling the two terminal alkynes 124 and 125 with cyclopropylideneacetamides 126 in the presence of Rh(I) complex. Regioselective insertion of 126 produces the intermediate СКАЧАТЬ