Addition of Heterocycles to Conjugate Unsaturated Carbonyl Compounds: Difunctional Derivatives

Webb, Irving D.; Borcherdt, G. T.

doi:10.1021/ja01146a074

Cited by 31 publications

(6 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The same reaction applied to the closely related adduct 3 was a key transformation in our recent synthesis (2) of ( 2 ) daunomycinone. An examination of the process with a variety of oxabicyclo adducts' was conducted and the results (Table 1, Entries 1, 3, 6, 8, 1 1,13,16,18) confirmed the generality of the reaction. A reverse-Michael rationalization shown in Scheme 1 requires the development of some double bond character at a bridgehead and is also a 5-endo-trig reversal in violation of rules (3) formulated earlier and illustrated (4) with the furan 9.…”

mentioning

confidence: 85%

Anomalous 5-endo-trig reversals: general reactions of 7-oxabicyclo[2.2.1]heptenes and heptanes

Keay¹,

Rajapaksa²,

Rodrigo³

1984

Can. J. Chem.

View full text Add to dashboard Cite

. 1093 (1984).Two general 5-endo-trig reversals of 7-oxabicyclo[2.2, llheptanes and heptenes are described and discussed. The reverseMichael reaction occurs with the aldehyde, ketone, ester, and nitrile derivatives while the reverse aldol reaction catalysed by acid is confined to the aldehydes and ketones. These properties of the title compounds are rationalized in terms of the geometric alignments of the bonding and antibonding orbitals of the bridging oxygen atom and its neighboring carbons. New isobenzofuran and cyclohexadiene syntheses form a part of the report. Early in our studies of the Diels-Alder reactions of isobenzofurans (1) we made the useful and intriguing discovery that adduct l a was smoothly converted to the dihydronaphthalene 2 a with methanolic sodium methoxide. The same reaction applied to the closely related adduct 3 was a key transformation in our recent synthesis (2) of ( 2 ) daunomycinone. An examination of the process with a variety of oxabicyclo adducts' was conducted and the results (Table 1, Entries 1, 3, 6, 8, 1 1,13,16,18) confirmed the generality of the reaction. A reverse-Michael rationalization shown in Scheme 1 requires the development of some double bond character at a bridgehead and is also a 5-endo-trig reversal in violation of rules (3) formulated earlier and illustrated (4) with the furan 9. No evidence could be obtained, however, to support any alternative mechanism; for example, no products of C(4)-0 cleavage were ever observed, thus excluding the possibility of a simple nucleophilic displacement at C ( l ) and(or) C(4). Deuteration at C(2) took place with esters and nitriles (entries 5, 7 , 10, 12, 15, and 17) and the deuterated products were endo-exo mixtures even when pure endo substrates ( l c and I d , entries 5 and 7) were used. Oxabicyclo ketones and aldehydes could not be deuterated cleanly with methanolic methoxide because of the rapid formation of products under the conditions. After 1 h at 20°C with this reagent, l a and l b , for example, were converted to a 1 : 1 mixture of products (2a and 2 b respectively) and deuterated starting materials. The lower acidity of the esters and nitriles must be responsible for rapid reprotonation of their enolates in methanolic methoxide, permitting clean deuteration in these cases and revealing the existence of a kinetic barrier to the reverse-Michael fission of the C(1)-0 bond. This behaviour is similar to the previously observed (4) deuteration of furan 9 and is interpreted similarly. Unlike the simple furan 9, however, which was inert to all bases, these compounds do suffer a forbidden 5-endo-trig cleavage with the strong base LDA under aprotic conditions (entries 6, 8, 1 1, 13, 16, and 18). Base-catalysed aromatizations observed in entries I Author to whom correspondence may be addressed. 'prepared by Diels-Alder reaction of furans and isobenzofurans with the appropriate dienophiles and used as endo-exo mixtures.2, 4, and 9 and previously with sodium acetate in refluxing methanol (5) must also occur through an initial ...

show abstract

mentioning

confidence: 85%

Anomalous 5-endo-trig reversals: general reactions of 7-oxabicyclo[2.2.1]heptenes and heptanes

Keay¹,

Rajapaksa²,

Rodrigo³

1984

Can. J. Chem.

View full text Add to dashboard Cite

show abstract

“…[20] First, we investigated the uncatalyzed conjugated addition reaction between 2-methylthiophene (2a)a nd enone 1a.O ur results indicated that this reaction had av ery high activation barriero f4 0.4 kcal mol À1 ,i ne xcellent agreement with our prior experimental results andl iterature reports that no background reaction occurred at ambient temperature. [21] In the transition state, enone 1a adopted an s-cis conformation and the carbonyl oxygen atom was very close to the a-CÀHh ydrogen atom of the thiopheneg roup, with an O···H distance of 2.005 .I ntrinsic reactionc oordinate (IRC) calculations indicated that the reactionf olloweda na synchronous concerted mechanism in which the formation of the CÀCb ond was immediately followed by protont ransfer from the thiophene moiety to the enone moiety, without the formationo fa no therwise-high-energyz witterionic intermediate. An enol was predicted to form as an intermediate, which subsequently tautomerized into the ketonep roduct (3aa).…”

Section: Computational Analysismentioning

confidence: 99%

Halogen‐Bonding‐Induced Conjugate Addition of Thiophenes to Enones and Enals

Hui

Heusler

et al. 2019

Chemistry An Asian Journal

View full text Add to dashboard Cite

Herein, we report the conjugate addition of a,bunsaturated carbonyl compounds to thiophene derivatives. We used a2 -iodoimidazolinium triflate salt as ah alogenbonding donor,w hich afforded moderate-to-excellent yields of the corresponding alkylated thiophenes. Insight into the catalytic process was obtained from 1 HNMR spectroscopy studies and DFT calculations, which indicated ah alogenbonding-supportedm echanism with limited Brønsted acid catalysis.

show abstract

“…This reaction is exemplified by the formation of the adducts (E13) and (E14) (X = H; Y = C0 2 R and COR) by the reaction of pyrrole with acrylic esters and vinyl ketones, (147)(148)(149)(150)(151)(152) whilst ß-aroylacrylic esters (153) and 4-vinylpyridine (154 ' 155) give the correspondingly substituted adducts. (E13)-f(E14).…”

Section: E C-alkylation Reactionsmentioning

confidence: 99%

Electrophilic Substitution of the Pyrrole Ring

1977

The Chemistry of Pyrroles

View full text Add to dashboard Cite

Addition of Heterocycles to Conjugate Unsaturated Carbonyl Compounds: Difunctional Derivatives

Cited by 31 publications

References 0 publications

Anomalous 5-endo-trig reversals: general reactions of 7-oxabicyclo[2.2.1]heptenes and heptanes

Anomalous 5-endo-trig reversals: general reactions of 7-oxabicyclo[2.2.1]heptenes and heptanes

Halogen‐Bonding‐Induced Conjugate Addition of Thiophenes to Enones and Enals

Electrophilic Substitution of the Pyrrole Ring

Contact Info

Product

Resources

About