Regioselective functionalization. .beta. Substituent effects on the regioselectivity of Baeyer-Villiger oxidations of 3-substituted 2-azabicyclo[2.2.2]octan-5-ones (isoquinuclidin-5-ones)

Krow, Grant R.; Johnson, Constance A.; Guare, James P.; Kubrak, Dennis; Henz, Kenneth J.; Shaw, Donald A.; Szczepanski, Steven W.; Carey, James T.

doi:10.1021/jo00148a002

“…HOSA and Schmidt Reactions. The ketones in Table were prepared by our previously described regioselective ketofunctionalization method from known azabicycloalkenes (see Experimental Section) . Beckmann rearrangements of the ketones were performed in the presence of HOSA in refluxing acetic acid or formic acid to afford lactams .…”

Section: Resultsmentioning

confidence: 99%

“…1 H NMR spectra were recorded at 100, 300, or 500 MHz, and 13 C NMR at 75 MHz in CDCl 3 solvent. Ketones 11 , 14 , 17 , 20 , 23 , 26 , and 29 were prepared by a previously described route from known alkenes; ,, the 3- anti stereochemical designation places the 3-substituent away from the carbonyl bridge. Lactam ratios of crude mixtures were determined by comparison of the integrated intensities of the resonances for the protons adjacent to carbonyl or the NH peaks.…”

Section: Methodsmentioning

confidence: 99%

Regioselective Functionalization. 7.¹ Unexpected Preferences for Bridgehead Migration in Schmidt Rearrangement Syntheses of Novel 2,6-Diazabicyclo[3.2.x]alkan-3-ones (x = 1−3)

Krow

¹

,

Szczepanski

²

,

Kim

³

et al. 1999

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Regioselective syntheses of 2,6-diazabicyclo[3.2.x]alkan-3-ones (x = 1−3) 34 by insertion of nitrogen next to the bridgehead (BH) of 2-azabicyclo[2.2.x]alkanones 32 with hydroxylamine-O-sulfonic acid are described. The ketones 32 under Schmidt reaction conditions (HN3/H2SO4) afford major amounts of BH migrated lactams 34 but also, when x = 2 or 3, the methylene (M) migrated lactams, 3,6-diazabicycl[3.2.x]alkan-2-ones 37. The present N-insertion reactions favoring BH migration with azabicyclic ketones contrast markedly with reactions of the related carbocycles 1a , b, which give only methylene migrated lactams 2a , b with HN3/H2SO4. Schmidt reactions of 3-anti/syn-methyl- and 3-anti-phenyl-2-azabicyclo[2.2.2]octan-5-ones 17, 20, and 23 (64:36 ± 9, BH:M) follow the reaction pattern of the parent ketone 14, but the 3-syn-phenyl ketone 26 gives major (65%) methylene migration. The results offer insights into the BH vs M migration dichotomy for the Beckmann and Schmidt reactions of bridged bicyclic ketones.

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“…To avoid the purification of the latter sensitive cyclobutanones, their direct functionalization by a stereospecific transformation, such as a Baeyer–Villiger oxidation was envisaged 24. Thus, treatment of cyclobutanone 13 (d.r.=88:12) with peracetic acid (AcOOH, AcONa, AcOH, room temperature)24b provided the desired γ‐lactone 15 (65 %) without alteration of its diastereomeric purity owing to the well‐known stereospecificity of the Baeyer–Villiger reaction (Scheme 3) 24. 25…”

Section: Methodsmentioning

confidence: 99%

Diastereoselective Gold‐Catalyzed Cycloisomerizations of Ene‐Ynamides

Couty

¹

,

Meyer

²

,

Cossy

³

2006

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Metal-catalyzed cycloisomerizations of ene-ynes lie among the most powerful methods for the elaboration of cyclic or polycyclic organic compounds. [1] In recent years, achievements in the field of platinum- [2][3][4][5][6] and gold-catalyzed [7][8][9][10][11][12][13][14] cycloisomerizations of ene-ynes have been particularly noteworthy. As a result of their high reactivity and mild reaction conditions, gold(I) salts or complexes are currently emerging as the most promising catalysts for these reactions.[15]Whereas the gold-catalyzed cycloisomerizations of ene-ynes accommodate the presence of oxygen or nitrogen atoms in the tether, [7a-c] and enol ethers as nucleophilic partners, [7a, 9b] eneynamines [5d,e] and ene-ynol ethers [10b] have been seldom considered as substrates. Herein, we report the first examples of gold-catalyzed cycloisomerizations of 1,6-ene-ynamides that lead to substituted cyclobutanones or azabicyclic compounds, depending on the substitution pattern, and proceed with high levels of diastereoselectivity.The platinum(II)-catalyzed cycloisomerization of eneynamides has already been investigated. [5d,e] Little difference, in terms of reactivity relative to the non-heterosubstituted series, was apparent for the most simple 1,6-ene-ynamide 1, which was converted into the so-called "formal metathesis product" 2 (98 %).[16] By contrast, the platinum(II)-catalyzed cycloisomerization of the homologous 1,7-ene-ynamide 3 led to the cyclobutene intermediate 4, which was isolated in rather low yield (34 %), and the latter was therefore best hydrolyzed directly to the corresponding cyclobutanone 5 (65 %).[5d,e] Compounds 2 and 4 were assumed to originate from a cyclopropyl platinum carbene intermediate of type A (M = PtCl 2 ). [3, 4,14] The latter underwent ring expansion to the cyclobutylcation B, stabilized by the nitrogen atom, [17] and demetalation afforded the cyclobutene intermediate of type C. For 1,6-ene-ynamides such as 1, it was suggested that the double bond in the cyclobutene of type C (n = 1) remained in the more stable exo position but that this intermediate underwent electrocyclic ring opening to afford the 1,3-diene 2. However, recent mechanistic investigations suggest that the formation of 1,3-dienes, such as 2, may result from the skeletal rearrangements of the cyclopropyl metal carbenes of type A (n = 1) via intermediates of type D and/or E. [14] In the case of 1,7-ene-ynamides such as 3, the migration of the double bond to the more stable endo position took place, thus resulting in lower ring strain, and led to the cyclobutene 4. As a consequence of the platinum-catalyzed reaction pathways, any stereocenter generated in the initial stages of the cycloisomerization in the metal carbene of type A would be lost in subsequent steps (Scheme 1).The use of milder reaction conditions should enable the rate of the skeletal rearrangements of the cyclopropyl metal carbene of type A to be decreased and/or avoid the electrocyclic ring opening of the intermediate cyclobutene of type C, both of wh...

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“…To avoid the purification of the latter sensitive cyclobutanones, their direct functionalization by a stereospecific transformation, such as a Baeyer-Villiger oxidation was envisaged. [24] Thus, treatment of cyclobutanone 13 (d.r. = 88:12) with peracetic acid (AcOOH, AcONa, AcOH, room temperature) [24b] provided the desired g-lactone 15 (65 %) without alteration of its diastereomeric purity owing to the well-known stereospecificity of the Baeyer-Villiger reaction (Scheme 3).…”

mentioning

confidence: 99%

“…= 88:12) with peracetic acid (AcOOH, AcONa, AcOH, room temperature) [24b] provided the desired g-lactone 15 (65 %) without alteration of its diastereomeric purity owing to the well-known stereospecificity of the Baeyer-Villiger reaction (Scheme 3). [24,25] When the gold-catalyzed cycloisomerization and the Baeyer-Villiger oxidation were carried out subsequently starting from ynamide 10, without purification of the intermediate cyclobutanone 13, the resulting g-lactone 15 was isolated in a satisfactory overall yield (65 %) and as a single diastereomer (d.r. > 95:5), thereby indicating the intrinsic high diastereoselectivity of the gold-catalyzed cycloisomerization.…”

mentioning

confidence: 99%

Diastereoselective Gold‐Catalyzed Cycloisomerizations of Ene‐Ynamides

Couty

¹

,

Meyer

²

,

Cossy

³

2006

View full text Add to dashboard Cite

Metal-catalyzed cycloisomerizations of ene-ynes lie among the most powerful methods for the elaboration of cyclic or polycyclic organic compounds. [1] In recent years, achievements in the field of platinum- [2][3][4][5][6] and gold-catalyzed [7][8][9][10][11][12][13][14] cycloisomerizations of ene-ynes have been particularly noteworthy. As a result of their high reactivity and mild reaction conditions, gold(I) salts or complexes are currently emerging as the most promising catalysts for these reactions.[15]Whereas the gold-catalyzed cycloisomerizations of ene-ynes accommodate the presence of oxygen or nitrogen atoms in the tether, [7a-c] and enol ethers as nucleophilic partners, [7a, 9b] eneynamines [5d,e] and ene-ynol ethers [10b] have been seldom considered as substrates. Herein, we report the first examples of gold-catalyzed cycloisomerizations of 1,6-ene-ynamides that lead to substituted cyclobutanones or azabicyclic compounds, depending on the substitution pattern, and proceed with high levels of diastereoselectivity.The platinum(II)-catalyzed cycloisomerization of eneynamides has already been investigated. [5d,e] Little difference, in terms of reactivity relative to the non-heterosubstituted series, was apparent for the most simple 1,6-ene-ynamide 1, which was converted into the so-called "formal metathesis product" 2 (98 %).[16] By contrast, the platinum(II)-catalyzed cycloisomerization of the homologous 1,7-ene-ynamide 3 led to the cyclobutene intermediate 4, which was isolated in rather low yield (34 %), and the latter was therefore best hydrolyzed directly to the corresponding cyclobutanone 5 (65 %).[5d,e] Compounds 2 and 4 were assumed to originate from a cyclopropyl platinum carbene intermediate of type A (M = PtCl 2 ). [3, 4,14] The latter underwent ring expansion to the cyclobutylcation B, stabilized by the nitrogen atom, [17] and demetalation afforded the cyclobutene intermediate of type C. For 1,6-ene-ynamides such as 1, it was suggested that the double bond in the cyclobutene of type C (n = 1) remained in the more stable exo position but that this intermediate underwent electrocyclic ring opening to afford the 1,3-diene 2. However, recent mechanistic investigations suggest that the formation of 1,3-dienes, such as 2, may result from the skeletal rearrangements of the cyclopropyl metal carbenes of type A (n = 1) via intermediates of type D and/or E. [14] In the case of 1,7-ene-ynamides such as 3, the migration of the double bond to the more stable endo position took place, thus resulting in lower ring strain, and led to the cyclobutene 4. As a consequence of the platinum-catalyzed reaction pathways, any stereocenter generated in the initial stages of the cycloisomerization in the metal carbene of type A would be lost in subsequent steps (Scheme 1).The use of milder reaction conditions should enable the rate of the skeletal rearrangements of the cyclopropyl metal carbene of type A to be decreased and/or avoid the electrocyclic ring opening of the intermediate cyclobutene of type C, both of wh...

show abstract

Regioselective functionalization. .beta. Substituent effects on the regioselectivity of Baeyer-Villiger oxidations of 3-substituted 2-azabicyclo[2.2.2]octan-5-ones (isoquinuclidin-5-ones)

Cited by 20 publications

References 0 publications

Regioselective Functionalization. 7.¹ Unexpected Preferences for Bridgehead Migration in Schmidt Rearrangement Syntheses of Novel 2,6-Diazabicyclo[3.2.x]alkan-3-ones (x = 1−3)

Regioselective Functionalization. 7.¹ Unexpected Preferences for Bridgehead Migration in Schmidt Rearrangement Syntheses of Novel 2,6-Diazabicyclo[3.2.x]alkan-3-ones (x = 1−3)

Diastereoselective Gold‐Catalyzed Cycloisomerizations of Ene‐Ynamides

Diastereoselective Gold‐Catalyzed Cycloisomerizations of Ene‐Ynamides

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Regioselective functionalization. .beta. Substituent effects on the regioselectivity of Baeyer-Villiger oxidations of 3-substituted 2-azabicyclo[2.2.2]octan-5-ones (isoquinuclidin-5-ones)

Cited by 20 publications

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Regioselective Functionalization. 7.1 Unexpected Preferences for Bridgehead Migration in Schmidt Rearrangement Syntheses of Novel 2,6-Diazabicyclo[3.2.x]alkan-3-ones (x = 1−3)

Regioselective Functionalization. 7.1 Unexpected Preferences for Bridgehead Migration in Schmidt Rearrangement Syntheses of Novel 2,6-Diazabicyclo[3.2.x]alkan-3-ones (x = 1−3)

Diastereoselective Gold‐Catalyzed Cycloisomerizations of Ene‐Ynamides

Diastereoselective Gold‐Catalyzed Cycloisomerizations of Ene‐Ynamides

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Regioselective Functionalization. 7.¹ Unexpected Preferences for Bridgehead Migration in Schmidt Rearrangement Syntheses of Novel 2,6-Diazabicyclo[3.2.x]alkan-3-ones (x = 1−3)

Regioselective Functionalization. 7.¹ Unexpected Preferences for Bridgehead Migration in Schmidt Rearrangement Syntheses of Novel 2,6-Diazabicyclo[3.2.x]alkan-3-ones (x = 1−3)