Lithium-halogen exchange-initiated cyclization reactions. 3. Intramolecular conjugate addition reactions of unsaturated acylphosphoranes

Abstract

The lithium-halogen exchange-initiated intramolecular conjugate addition reactions of some model unsaturated acylphosphoranes have been examined. The effects of halide type, chain length, and acceptor substitution pattern on the feasibility of ring construction were studied. The lithium-bromine exchange reactions in two 2-bromoaryl acceptors were found to be too slow, relative to competing side reactions, to allow practical carbocycle syntheses while 3-, 4-, 5-, and 6-membered carbocycles are formed in good to excellent yields from precursors that are vinyl m d saturated primary iodides. Highly efficient intramolecular conjugate addition reactions to @&disubstituted acceptor units are possible, and intermediate anions from intramolecular conjugate addition reactions are readily captured with electrophiles.Lithium-halogen exchange reactions provide an important method for the introduction of nucleophilic cent e r~.~ While the mechanistic aspects of these reactions are not entirely clear: many exchange reactions appear to be quite rapid, even a t low temperatures. We are currently studying cyclization reactions of the type shown in Scheme I where nucleophilic centers introduced through lithium-halogen exchange reactions subsequently undergo intramolecular bond-forming reactions with an internal electrophilic center. The successful execution of such schemes requires that both the exchange reaction and the cyclization reaction be faster than any irreversible reaction between the metalating reagent and the electrophilic center. Largely through the pioneering work of Parham and co-workers, lithium-halogen exchange reactions in aromatic systems have been shown to be possible in the presence of a variety of common electrophilic groups (COO-, COOR, CN, CONR2, CX, C=NR, N02h5 On the (1) Part 2: Cooke, M. P., Jr.; Houpis, I. N. Tetrahedron Lett. 1986, (2) Present address: College of Southern Idaho, Twin Falls, ID 83301. (Scheme I Scheme I1 I e basis of these studies, a number of exchange-initiated cyclization reactions have been described including cyclialkylation reactions of halide^,^,^ epoxides,' ketones,' and (5) Parham, W. E.; Bradsher, C. K.

Chiral Aminated α‐Methylenebenzocycloalkenes from o‐Bromoaryl Aldehydes and Ketones

“…Compound 1g 8 was prepared by the oxidation of commercially available o ‐bromobenzyl alcohol with Dess–Martin periodinane. Compounds 1h , 1i ,9 and 1l 10 were prepared from o ‐bromoiodobenzene through a palladium‐catalyzed coupling reaction with allyl alcohol, but‐3‐en‐1‐ol, and but‐3‐en‐2‐ol, respectively.…”

Synthesis of a Polymerizable Benzocyclobutene that Undergoes Ring-Opening Isomerization at Reduced Temperature

“…18,19 Due to the many routes for converting 4-bromobenzocyclobutene into vinylbenzocyclobutene, 7,9,14,15 we considered the three possible starting materials shown in Scheme 2 for synthesizing 4bromo-1-ethoxybenzocyclobutene via a benzyne intermediate. Since iodine exchanges faster than bromine in lithium-halogen exchange using n-butyllithium, 20 4-bromo-2fluoroiodobenzene would be the most direct reagent for synthesizing 4-bromo-1-ethoxybenzocyclobutene if metal-iodine exchange with either n-butyllithium or possibly the Grignard reagent occurs selectively, thereby generating the benzyne by elimination of lithium fluoride (LiF) or magnesium bromide fluoride (MgBrF), respectively, in the presence of ethyl vinyl ether. However, the conver-sions were low.…”

2-(2-Bromoethyl)-1,3-dioxane

“…38, 50 Cuprate formation also results in successful condensation with allylic acetates (eq 23), 51,52 epoxides, 53 vinyl epoxides (eq 24), 54 and alkynes (eq 25). 55 Conjugate addition to α,β-unsaturated ketones can also be realized in this way, 56 this process often constituting the first step of an annulation sequence.…”