Geminal diesters

With this revision in our original plans, both alkenes and allenes were found to undergo efficient cycloadditions to produce cyclooctenone products in a new [6+2] cycloaddition process. This novel cycloaddition has been shown to proceed efficiently with alkenes tethered with sulfonamide, ether, or geminal diester Hnkers (Tab. 13.15, see page 294). Isomerization of the olefin, a potential competing reaction in this process, is not observed. Methyl substitution of either alkene in the substrate is well tolerated, resulting in the facile construction of quaternary centers. Of mechanistic importance, in some cases cycloheptene byproducts were isolated from [6+2] cycloaddition reactions in addition to the expected cyclooctenone products (that is, entries 3 and 4). 

Banks (151) has reported the decarbalkoxylation (NaCl in wet DMSO at 148-153°C) of the geminal diesters 490 and 493. He found that the reaction of 490 was highly stereoselective yielding the axial isomer 491 in preference to the more stable equatorial isomer 492 (ratio =9 1). On the other hand, the reaction of 493 was non-stereoselective (ratio =1 1 of 494 and 495). 

One possible mechanism is the following. The allenyl geminal diester 61, not isolable, is expected to be susceptible to Michael-type addition of Pd(0)L species to... 

Decarboaikybuion. Geminal diesters are decarboalkylated in 90-95 % yield when heated at 140-180° for several hours with a slight excess of sodium chloride (tabic salt is satisfactory) in DMSO containing 2 moles of water per mole of substrate. 

One possible mechanism is the following. The allenyl geminal diester 70 is expected to be susceptible to Michael-type addition of LnPd(O) species to the allenyl sp carbon, resulting in the formation of the palladacyclopropane 71. Insertion of carbon monoxide into 71 and methanolysis afford the triester 72 (Scheme 11-20). The alkene geometry of the product 72 is exclusively E. The high stereoselectivity can be rationalized by assuming that a nucleophilic attack of Pd(0) species on the allenyl sp carbon in 70 takes place from the less-hindered side of a smaller alkyl substituent (R ). Needless to say, in allene 70, the two ester groups are perpendicular to the two substituents Rl and Rg. 

The strong prevalence for allyl radicals to cyclize in 5-exo fashion as well as the accelerating effect of geminal diester substitution was also observed in iodide atom transfer reactions of ally lie iodides. The ratio of S-exo to 6-endo product is even higher than for hydrogen trapping, probably also due to the lower temperature in this photolytically initiated reaction (equation 6). Allylic dimers were again isolated as side products. No... 

Krapcho, A. P., Lovey, A. J. Decarbalkoxylations of geminal diesters, P-keto esters, and a-cyano esters effected by sodium chloride in dimethyl sulfoxide. Tetrahedron Lett. 1973, 957-960. 

Krapcho, A. P., Weimaster, J. F., Eldridge, J. M., Jahngen, E. G. E., Jr., Lovey, A. J., Stephens, W. P. Synthetic applications and mechanism studies of the decarbalkoxylations of geminal diesters and related systems effected in dimethyl sulfoxide by water and/or by water with added salts. J. Org. Chem. 1978,43, 138-147. 

Krapcho, A. P., Weimaster, J. F. Stereochemistry of decarbalkoxylation of cyclic geminal diesters effected by water and lithium chloride in dimethyl sulfoxide. J. Org. Chem. 1980,45, 4105-4111. 

In 1967, Krapcho reported the utility of a method for decarboxylating geminal diesters using a salt such as NaCN dissolved in a polar aprotic solvent like dimethyl sulfoxide (DMSO). The reaction was discovered when an attempt to effect the following substitution reaction with 1 resulted in decarbomethoxylation to give 2.2 Shortly thereafter, a comprehensive study of decarbalkoxylations using mono- and di-substituted malonates was published.3... 

Decarboalkylation of geminal diesters. DABCO is useful for cleavage of these diesters (equation I). 3-Quinuclidinol (I) is even more effective, but also more expensive. ... 

The same intermediary allenyl geminal diester would be extremely susceptible to an intramolecular ene process so that the second carbonylation process mentioned above is virtually interrupted (Scheme 18). ... 

Not surprisingly, the useful ester dealkylating agent MeaSil (see ref. 65) can be used for the decarboxylation of /3-keto-esters and geminal diesters the avoidance of exposure of the substrate to strong aqueous acid or base is an advantage with this method. Similar transformations can be effected by thermolysis (170— 190 °C) with boric acid. ... 

In 2000, inspired by the work of Liebeskind [31], Wender and co-workers reported [32] an intramolecular Rh-catalyzed [6-1-2] cycloaddition reaction between vinylcyclobutanone and terminal aUcenes (Scheme 5). In this transformation 5 mol% [Rh(CO)2Cl]2, 10 mol% PPhs, and 10 mol% AgOTf were employed and cyclooctenone 24 was afforded in 92% yield as a single diastereoisomer. Besides sulfonamides, other linkers such as ether and geminal diesters were also found to be compatible with this reaction condition using specified catalyst precursors. 

Potassium hydroxide in DMSO or DMSO-CF3SO3H is a useful base for the C-alkylation of geminal diesters as well as many other substrates both mono-and di-alkylation is possible. The reactions seem to be very simple to carry out particularly as the rigorous exclusion of water is not necessary. 

Decarboxylation.—Direct decarboxylation of hindered geminal diesters has been achieved using amine bases (DBN Dabco). This attractive one step process generally gives good yields and avoids the use of both acidic and aqueous conditions. An improved method for the oxidative decarboxylation of vicinal diacids to olefins employs copper(i) oxide and 2,2 -dipyridyl in quinoline temperatures of 180 °C are however required. Excellent yields have been achieved in the decarboxylation of bridgehead carboxylic acids by sequential bromination and photochemical reduction in the presence of tri-n-butyltin hydride. 

Decarbalkooiylotions of geminal diesters can be effected by treatment with sodium chloride in hot, wet dimethyIsulfoxide. Similar yields are obtained in the decarbethoxylation of both 8-keto and a-cynanoesters. 

Decarboxylation.—Krapcho s group has published details of a systematic study of the decarboxylation of geminal diesters and /3-keto-esters by the widely used wet dimethyl sulphoxide-salt method. Although optimum conditions are obviously substrate dependent, the system DMS0-H20-LiCl is often the best choice. When a similar decarboxylation of geminal diesters is carried out in hexamethylphosphoramide at ca. 155 C in the presence of diphenyl disulphide, a-phenylthioesters are generated in yields usually less than 60% f ... 

As a result of the cisitrans geometry of the imines, either 26-cis or 26-trans could be afforded, with 26-cfr being at a higher energy state. Intermediate 27a would afford the cfr-isomer by a Mannich ring closure and similarly intermediate 27b would afford the rrons-isomer. The positioning of the geminal diester should enable the retro-Mannich process to take place, which would leave a reasonable pathway for the less stable tram isomer to be converted to the more stable cis isomer. 

A final synthetic effort in the yohimbine alkaloid area concerns the studies reported by Loewenthal and his coworkers (Scheme 3.92) (143). The aim was to develop an efficient method to prepare the bicyclic enone 21, which serves as a key intermediate in the Woodward reserpine synthesis strategy (19). The route for preparation of 21 began with Friedel Crafts reaction of 2-methoxynaphthalene (523) with the oxalyl chloride equivalent 524, a process which afforded the acenaphthenoquinone 525. Oxidative-decarboxylation of 525 yielded the naphthalene-carboxylic acid 526 which was transformed by Birch reduction and esterification to the dihydro-derivative 527. Carboxyla-tion then provided geminal diester 528 which was epoxidized. Sequential lactonization and methylation afforded tricyclic lactone 529. Ester cleavage with subsequent decarboxylation gave lactone 530 which was demethylated to provide 531. While no further effort was given to the development of this... 

List documented another approach to effect catalytic enantioselective Pic-tet-Spengler reactions, using chiral phosphoric acids derived from BINOL [40-42, 133] (Equation 13) [134]. Treatment of substituted tryptamine 173 with aldehyde 174 in the presence of chiral Bronsted acid 175 afforded adduct 176 in 98% yield and 96% ee. List suggested that the operation of the Thorpe-lngold effect was critical for these systems. Thus, in the absence of geminal diester substitution (cf 177), aldol condensation to give 178 was observed exclusively. 

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