Synthesis of hetero- and carbocycles by nucleophilic substitution at sp2 carbon

Recent synthesis of thietanes

“…azaspiro [3.3]heptane was evaluated as inhibitor of kinases, insecticides, and acaricides, its sulfur analogue, 6-amino-2thiaspiro [3,3]heptane (28) was prepared from the cheap starting material 2,2-bis(bromo-methyl)propane-1,3-diol (11). Compound 11 was converted into 3-(tert-butoxycarbonyl)-1,1bis(hydroxymethyl)aminocyclobutane (25) in 6 steps. After the treatment of 25 with methanesulfonyl chloride, the obtained dimethanesulfonate 26 was reacted with sodium sulfide giving rise to 6-(tert-butoxycarbonyl)amino-2-thiaspiro [3.3]heptane (27), which was further transformed into the desired 6-amino-2thiaspiro [3,3]heptane (28) hydrogen chloride salt after the acidic deprotection [37] (Scheme 5).…”

“…When Narasaka and co-workers investigated the formal intramolecular nucleophilic substitution at sp 2 carbon centers for the preparation of oxygen, nitrogen, and sulfur-containing unsaturated five-membered heterocycles, they found that the method could be applied for the synthesis of 2-alkylidenethietanes. They obtained 2-phenethyl-4-(propan-2-ylidene)thietane (520) from 5-bromo-6-methyl-1-phenylhept-5-ene-3-thiol (519) as a substrate in 1,3-dimethyl-2-imidazolidinone (DMI) as solvent [25] (Scheme 121). They further applied the method to synthesize 2-phenethyl-4-(propan-2-ylidene)thietane (520) from S-(5-bromo-6-methyl-1phenylhept-5-en-3-yl)thioacetate (521) directly because K 2 CO 3 led to deacetylation of the acetyl group from the thioacetate 521, which was prepared from the corresponding alcohol and thiolacetic acid with the Mitsunobu reagent [153] (Scheme 122).…”

“…Phosphorodithioate has been applied in the synthesis of thietanes as a nucleophile and generated phosphorothioate as a leaving group [24]. Some other cyclization methods have been reported in the synthesis of thietanes as well [25] (Figure 2). This review covers the methods outlined in Figure 2 and also some miscellaneous methods for the synthesis of various thietane derivatives.…”

Synthesis of Heterocycles by Intramolecular Nucleophilic Substitution at an Electron‐Deficient sp2 Nitrogen Atom

“…[40] Moreover, based on the knowledge of heterocyclic chemistry, the well-known Boulton-Katritzky rearrangement can formally be written as an intramolecular nucleophilic substitution that proceeds according to a unimolecular one-step mechanism, [41][42][43][44] which, in turn, bears a resemblance to the recently investigated vinylic S N 2 reactions at carbon atoms. [45][46][47][48][49][50][51] On the basis of this knowledge, substitution of the sulfate leaving group by the amidate anion at the sp 2 -hybridized N2 nitrogen atom in 2 may proceed either by an S N 2π mechanism (out-of-plane nucleophilic attack) by interacting with the π* orbital of the imino group or by an S N 2σ mechanism (in-plane attack) in which the nucleophile interacts with the σ* orbital of the imino nitrogen of the N-O bond (Scheme 7). To gain a mechanistic insight into these processes, theoretical studies of the transition states were undertaken (see the Exp.…”

Concerted Nucleophilic Substitution Reactions at Vinylic Carbons

“…Some 4-toluenesulfonamides bearing haloalkenyl moieties have been subjected to cyclization. 19 Homoallylic 4toluenesulfonamide (E)-24 with an alkyl group at the aposition was treated with various bases in 1,3-dimethylimidazolidin-2-one (DMI). When sodium hydride was used as a base, dihydropyrrole 25 was obtained in 76% yield within one hour (Scheme 18).…”