The Conversion of Steroidal Ring B Lactones into Ortho Esters: Preparation of 7,7-Dimethoxy-6-oxaestra-1,3,5(10)-triene Derivatives

1998 ◽  
Vol 51 (11) ◽  
pp. 1003 ◽  
Author(s):  
David G. Bourke ◽  
David J. Collins
Keyword(s):  
Acetic Acid ◽  
Phenolic Acid ◽  
Sodium Methoxide ◽  
Reaction Sequence ◽  
Ortho Ester ◽  
Methyl Trifluoromethanesulfonate ◽  
Ortho Esters

17β-t-Butyldimethylsilyloxy-3-methoxy-6-oxaestra-1,3,5(10)-trien-7-one (1), prepared in three steps from 17b-hydroxy-3-methoxy-6-oxaestra-1,3,5(10),8-tetraen-7-one (5a), was converted via the corresponding phenolic acid into 1β-t-butyldimethylsilyloxy-5β-(2′-t-butyldimethylsilyloxy-4′-methoxyphenyl)-N,7aβ-dimethyl-N-phenyl-2,3,3aα,4,5,6,7,7a-octahydro-1H-indene-4α-carboxamide (17c). Subjection of (17c) to a reaction sequence with methyl trifluoromethanesulfonate, sodium methoxide/methanol, and then dry methanol/acetic acid gave a low yield (12%) of the ortho ester 3,7,7,17β-tetramethoxy- 6-oxaestra-1,3,5(10)-triene (2b), together with 5β-(2′-hydroxy-4′-methoxyphenyl)-1β-methoxy-N,7aβ-dimethyl-N-phenyl-2,3,3aα,4,5,6,7,7a-octahydro-1H-indene-4α-carboxamide (17e) (29%), 8% of (17a), the 1β-hydroxy analogue of (17e) and 3% of methyl 5-(2′-hydroxy-4′-methoxyphenyl)-1β-methoxy-7aβ-methyl-2,3,3aα,4,5,6,7,7a-octahydro-1H-indene-4α-carboxylate (11c). The outcome of this reaction sequence was complex, and very sensitive to minor changes in conditions. Several related transformations are described, and possible mechanistic pathways are discussed.

scholarly journals Four New Sesquiterpenoids from Ligularia subspicata Collected in China; Isolation of a Bakkane-type Lactone, an Eremophilane-type Lactone, and Two Ortho Esters

2015 ◽  
Vol 10 (6) ◽  
pp. 1934578X1501000
Author(s):  
Yoshinori Saito ◽  
Takanori Otsubo ◽  
Yuko Iwamoto ◽  
Katsuyuki Nakashima ◽  
Yasuko Okamoto ◽  
...  
Keyword(s):  
Sichuan Province ◽  
Ortho Ester ◽  
Type Compound ◽  
Ortho Esters ◽  
First Time

A bakkane type lactone, an eremophilane type lactone, and two ortho esters were isolated from Ligularia subspicata collected in Sichuan Province, China. The ortho ester type compound has been isolated from Ligularia for the first time.

Hydrolysis of trioxaadamantane ortho esters. I. Dialkoxycarbocation – ortho ester equilibrium and acidity function

1984 ◽  
Vol 62 (6) ◽  
pp. 1068-1073 ◽  
Author(s):  
Robert A. McClelland ◽  
Patrick W. K. Lam
Keyword(s):  
Acid Concentration ◽  
Intramolecular Interaction ◽  
Uv Spectroscopy ◽  
Equilibrium Constants ◽  
Hydrolysis Product ◽  
Acidity Function ◽  
Ortho Ester ◽  
Aromatic Substituent ◽  
Ortho Esters ◽  
Hydrolysis Of

3-Aryl-2,4,10-trioxaadamantane ortho esters (T) undergo a rapid equilibration with a ring-opened dioxan-2-ylium ion (DH+) prior to hydrolysis to product (a 1,3,5-cyclohexanetriol monobenzoate). The cation is stable in concentrated H2SO4 solutions where it has been characterized by nmr spectroscopy. It is observed using uv spectroscopy in dilute acids, and the ratio [DH+]/[T] at equilibrium has been measured as a function of acidity. Reversibility of the ring opening is established by the pattern of plots of cation absorbance versus acid concentration and by the observation that solutions containing cation on neutralization or dilution yield ortho ester, not hydrolysis product. Equilibrium constants for the reaction [Formula: see text] have been measured by obtaining the acidity function HT for this system. The effects of the aromatic substituent and the steepness of the acidity function plot versus acid concentration are interpreted in terms of a strong intramolecular interaction in the cation between the cationic center and the hydroxyl oxygen.

Enolic Ortho Esters. I. Preparation and Birch Reduction of Some Coumarinoid Ortho Esters

1989 ◽  
Vol 42 (8) ◽  
pp. 1235 ◽  
Author(s):  
DJ Collins ◽  
LM Downes ◽  
AG Jhingran ◽  
SB Rutschmann ◽  
GJ Sharp
Keyword(s):  
Carbon Tetrachloride ◽  
Acid Hydrolysis ◽  
Boron Trifluoride ◽  
Boron Trifluoride Etherate ◽  
High Yield ◽  
Ortho Ester ◽  
Birch Reduction ◽  
High Yields ◽  
Ortho Esters ◽  
Hydrolysis Of

Phenolic ortho esters such as 4′,4′-dimethylspiro[2H-1-benzopyran-2,2′-[1,3]dioxolan] (7b) and 4′,4′-dimethyl-3,4-dihydrospiro[2H-1-benzopyran-2,2′-[1,3]dioxolan] (9c) were prepared in low yields by reaction of 2H-1-benzopyran-2-one (5) or 3,4-dihydro-2H-1-benzopyran-2-one (8a) with 2,2-dimethyloxiran in carbon tetrachloride in the presence of boron trifluoride etherate. 3,4-Dihydrospiro[2H-1-benzopyran-2,2′-[1,3] dioxoan ] (9a) and the corresponding 7-methoxy compound (9e) were obtained in high yield by reaction of (8a) or its 7-methoxy analogue (8b) with 1,2-bis(trimethylsily1oxy)ethane (10) in the presence of trimethylsilyl trifluoromethane-sulfonate . Birch reduction of phenolic ortho esters such as (9c) and (9e) afforded the enolic ortho esters 4′,4′-dimethyl-3,4,5,8-tetrahydrospiro[2H-1-benzopyran-2,2′-[1,3] dioxola n] (11a) and 7-methoxy-3,4,5,8-tetrahydrospiro[2H-1-benzopyran-2,2′-[1,3]dioxolan] (llc) in high yields. Birch reduction of 4′,4′,5′,5′-tetramethylspiro[2H-1-benzopyran-2,2′-[1,3]dioxolan] (7c) gave a 1 : 3 mixture of 4′,4′,5′,5′-tetramethyl-3,4-dihydrospiro[2H-1-benzopyran-2,2′-[l,3] dioxolan ] (9d) and the corresponding 3,4,5,8-tetrahydro compound (11b). Acid hydrolysis of the enolic ortho ester (11a) gave 67% of 2-hydroxy-2-methylpropyl 3-(2-oxocyclohex-3-enyl) propanoate (20).

Enolic Ortho Esters. VII Involvement of Magnesium Halides as Lewis Acids in the Reaction of Grignard Reagents with 1,6-Dideoxy- 1,1-ethylenedioxy-2,3,4-tri-O-methyl-D-xylo-hex-5- enopyranose and its 6-Phenyl Derivative: a Correction

1998 ◽  
Vol 51 (8) ◽  
pp. 681 ◽  
Author(s):  
David J. Collins ◽  
Angus I. Hibberd ◽  
Brian W. Skelton ◽  
Allan H. White
Keyword(s):  
Single Crystal ◽  
Lewis Acids ◽  
Titanium Tetrachloride ◽  
Grignard Reagents ◽  
Ortho Ester ◽  
X Ray ◽  
Phenyl Derivative ◽  
Methylmagnesium Iodide ◽  
Ortho Esters ◽  
Phenylmagnesium Bromide

The known aldehyde methyl 2,3,4-tri-O-methyl-α-D-gluco-hexodialdo-1,5-pyranoside (9) was converted in eight steps into the 6-phenyl glucose-derived enolic ortho ester (Z)-1,6-dideoxy-1,1-ethylenedioxy- 2,3,4-tri-O-methyl-6-phenyl-D-xylo-hex-5-enopyranose (22), the geometry of which was established by a single-crystal X-ray study. Treatment of the 6-phenyl enolic ortho ester (22) with titanium tetrachloride at –78° effected clean rearrangement into (2R/S,4R,5R,6S)-3,3-ethylenedioxy-4,5,6-trimethoxy-2-phenylcyclohexanone (26). Reaction of (22) with methylmagnesium iodide gave (1R,2S,4R,5S,6S)-3,3-ethylenedioxy-4,5,6-trimethoxy-1-methyl-2-phenylcyclohexanol (24), the structure and stereochemistry of which were established by an X-ray study. Reaction of (22) with phenylmagnesium bromide gave (25), the 1-phenyl analogue of (24). The firmly established structure of (24) led to proof both chemically and by X-ray means that the product from reaction of 1,6-dideoxy-1,1-ethylenedioxy-2,3,4-tri-O-methyl-D-xylo-hex-5-enopyranose (5) with methylmagnesium iodide has the hydroxy acetal structure (7) rather than the originally assigned hemiacetal structure (3).

Reversible ring opening in the hydrolysis of spiro ortho esters

1985 ◽  
Vol 63 (10) ◽  
pp. 2673-2678 ◽  
Author(s):  
Robert A. McClelland ◽  
Claude Moreau
Keyword(s):  
Rate Constant ◽  
Rate Constants ◽  
Ring Opening ◽  
Lone Pair ◽  
Order Rate Constant ◽  
Product Analysis ◽  
Ortho Ester ◽  
First Order ◽  
Order Rate ◽  
Ortho Esters

Hydrolysis kinetics are reported for four spiro ortho esters: 3,4-dihydro-6-methoxy-1H-2-benzopyran-1-spiro-2′-1′,3′-dioxolane (13), its 1′,3′-dioxane analog (14), and the 6-unsubstituted versions of each (11 and 12). For comparison, also included are the diethoxy analogs: 1,1-diethoxy-3,4-dihydro-6-methoxy-1H-2-benzopyran (10) and the 6-unsubstituted compound (9). Product analysis implicates an initial opening of the dioxolane or dioxane ring in the spiro ortho esters, as expected on the basis of stereoelectronic considerations. The intermediate dialkoxycarbocations can be observed in HCl solutions. A detailed analysis has been carried out for the 6-methoxy systems to provide the rate constants k1, the second-order rate constant for H+-catalyzed formation of the cation from the ortho ester, k2, the first-order rate constant for water addition to the cation, and k−1, the first-order rate constant for ring closing of the cation to reform the ortho ester. The two spiro ortho esters are shown in this analysis to undergo reversible ring opening in their hydrolysis, in that values of k−1, are greater than k2. The differences, however, are not large, k−1/k2 being 1.2 (dioxolane, 13) and 3.8 (dioxane, 14). Comparison with the diethoxy ortho ester also reveals that the ring opening process (k1, rate constants) is inherently more difficult with the dioxolane, although not with the dioxane. An argument involving lone pair orientation is advanced to explain this.

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