New Samarium Diiodide-Induced Ketyl Couplings - From Analogous Reactions to Serendipitously Discovered Processes

Abstract

Analogous applications of samarium diiodide as a promoter for ketyl cyclizations led to the discovery of several new and synthetically interesting reactions. Whereas samarium ketyl cyclizations with alkyne and allene units could be expected -though they have not been known before -the unplanned cyclization of the ketyl towards an aromatic ring uncovered a new mode of reaction. The resulting hexahydronaphthalene derivatives were formed in excellent diastereoselectivities and are synthetically very valuable building blocks. This new method was systematically investigated and extended to polycyclic compounds and those with heteroatoms in the spacer between the carbonyl group and the aromatic ring. The cyclizations involving indole and pyrrole derivatives are most promising for the stereoselective construction of alkaloid skeletons.

Efficient Synthesis of Medium‐Sized Rings Incorporating Indole or Pyrrole Units by Samarium Diiodide Induced Cyclizations

“…We recently suggested1b,2,3 that the high degree of diastereoselectivity for this type of cyclization should be due to a highly ordered cyclic transition structure of the ketyl addition to the (het)aryl ring in which the samarium alcoholate prefers the sterically more favourable equatorial position (Scheme ). This model nicely explains the relative configuration of the stereogenic centres within the seven‐membered ring.…”

Stereoselective synthesis of tricyclic compounds by intramolecular palladium-catalyzed addition of aryl iodides to carbonyl groups

“…For our systematic studies on samarium diiodide promoted cyclizations leading to benzannulated medium-sized rings [ 1 – 4 ] we required starting materials such as alkenyl-substituted compounds B ( Scheme 1 ). Obvious precursors for B are aryl iodides A that smoothly undergo palladium-catalyzed coupling reactions to provide the desired products.…”

Mechanistic Aspects and Synthetic Applications of Radical Additions to Allenes

“…This regioselectivity is attributed to the match between the more electrophilic character of the distal allene double bond and the nucleophilic samarium ketyl. 61,62 In 2007, the Huang group developed a Mn(OAc) 3 -mediated oxidative free-radical addition of dimethyl malonate or ethyl cyanoacetate to allenes 107 to furnish furan-2(5H)-ones or dimethyl 2-(2-oxoethylidene)malonates 108 (Scheme 43) as the major products. 63 In the presence of 4.5 equiv of Mn(OAc) 3 •2H 2 O, as opposed to 2.5 equiv, the allene 109 was converted to the noncyclized product 110 (Scheme 44).…”

“…The attack of the carbonyl oxygen on the terminal allene carbon in the more stable allyl cation 66 eventually affords the desired product 60. In both mechanisms, the heteroatom linkage (O, N, S) on the allene 59 is important for the effective stabilization of proposed intermediates in pathway I (62) and pathway II (66).…”