Regiodivergent Ring-Opening Reaction of Trichloromethylcyclopropane Carboxylates

Abstract

Reagent-controlled regiodivergent ring-opening reactions of trichloromethylcyclopropane carboxylates have been developed. The regioselectivity of bond cleavage is completely controlled by the proper choice of silver salts; the treatment of trichloromethylcyclopropane with AgBF4 led to C2-C3 bond cleavage and fluorination to afford fluorinated β,γ-unsaturated ester with high stereoselectivity, while the reaction with AgOAc in THF gave a γ,δ-unsaturated ester through the reductive cleavage of the C1-C2 bond.

Radical Addition of SF5Cl to Cyclopropenes: Synthesis of (Pentafluorosulfanyl)cyclopropanes

“…Under these conditions, the radical chain addition of SF 5 Cl across the double bond of 1a proceeded smoothly, with perfect control of the regioselectivity, and delivered a diastereomeric mixture of β-chloro­(pentafluorosulfanyl)­cyclopropanes 2a and 2′a in a 90:10 ratio (78%, 5 mmol scale experiment). Analysis of the 1 H NMR spectrum of 2a and 2′a indicated a similar vicinal coupling constant between cyclopropyl protons H1 and H3 in both diastereomers, thereby confirming that addition of the SF 5 radical occurred at the less substituted carbon (C1) of cyclopropene 1a on the face opposite to the ester moiety at C3, as observed in other radical additions to cyclopro­pen­oates. , The resulting rapidly interconverting cyclopropyl radical intermediates 3a and 3′a suffer from a steric interaction between the (CH 2 ) 2 OTBDPS substituent and the SF 5 group (at C1) or the ester moiety (at C3), respectively. However, the less stable invertomer 3a should undergo a faster chlorine atom transfer from SF 5 Cl ( trans to the sterically demanding SF 5 substituent at C1) compared to that of 3′a .…”

“…Despite the potential interest in them, SF 5 -substituted cyclopropanes are still unknown compounds to the best of our knowledge. To date, the most general and practical entry to SF 5 -aliphatic compounds remains the radical addition of SF 5 Cl to alkynes or alkenes using Et 3 B as the initiator (Scheme A). , Cyclopropenes are known to behave as radical acceptors, as illustrated by the hydrostannylation of cyclopropenone acetals, the addition of carbon-centered electrophilic radicals generated from xanthates to similar substrates or cyclopropene gem -dicarboxylates, the addition of the trichloromethyl radical to cyclopropenoates, and the more recently disclosed radical carbocyanation reaction (Scheme B) …”

Regiodivergent Chlorine‐Atom‐Transfer Ring‐Opening Reactions of Trichloromethylcyclopropanes

“…Trichloromethylcyclopropanes 1a , b , d – g , 1i , and 1j were prepared according to literature procedures . For the synthesis of trichloromethylcyclopropane 1c and 1h , see the Supporting Information.…”

“…We recently reported the fluorinative and reductive ring‐opening reactions of trichloromethylcyclopropanes, which involve the silver‐promoted elimination of chloride from a trichloromethyl group triggering the ring‐opening of a cyclopropane ring . Unfortunately, this reaction is not atom‐economic, as it is stoichiometric in silver and proceeds with the loss of chlorine from the substrate.…”

Radical Cyclization of Trichloroacetamides: Synthesis of Lactams

“…Also recently, Ueda showed that AgOAc in THF was able to generate radicals to cyclize trichloroacetamide 1c to afford γ-lactam 76c in moderate yield (Scheme 57). 72 It was shown that Ag(I) was reduced to Ag(0), which would act as a radical initiator, and THF was again assumed to be the proton source.…”