Subject reaction with ketals

Fig (19) Octalin ketal (163) is converted to kete dithioacetal (164) by the cleavage of ketal function and condensation with carbon disulfide and methyl iodide. Subjection of (164) to the action of dimethylsulfonium niethylide and acid hydrolysis leads to the formation of unsaturated lactone (165).lts furan silyl ether derivative is caused to undergo Diets-Atder reaction with methyl acrylate to obtain salicyctic ester (166) which is converted by standard organic reactions toabietane ether (167). It is converted to aiiylic alcohol (168) by epoxidation and elimination. Alcohol (169) obtained from (168) yields orthoamide which undergoes transformation to amide (170). Its conversion to the previously reported intermediate has been achieved by epoxidation, elimination and hydrolysis. 

New and continuing efforts towards the total synthesis of dendrobine (59 R = H) have been reported.In one sequence (Scheme 8), the butyric acid (85) was readily transformed into the ketal (86), which was submitted to a Birch reduction and hydrolysis to yield the cyclohexenone (87) as the single diastereomeric product. Acid treatment of (87) gave a stereoisomeric mixture of products (88) which were not separated but subjected to reaction with base to give compound (89). The same compound was obtained directly by treatment of (87) with strong base (Michael and aldol condensations combined). After some discouraging results, the tricyclic compound (89) was transformed into the desired keto-acid (90) via an abnormal ozonolysis reaction. Compound (90) possesses the correct stereochemistry at three asymmetric centres required for elaboration of dendrobine (59 R = H). 

A new stereoselective synthesis of 1,2,3-trisubstituted cyclopentanes based on the Wag-ner-Meerwein rearrangement of a 7-oxabicyclo[2.2.1]heptyl 2-cation starts with the Diels-Alder product of maleic anhydride and a furan (78TL2165, 79TL1691). The cycloadduct was hydrogenated and subjected to methanolysis. The half acid ester (47) was then electrolyzed at 0 °C to generate a cationic intermediate via the abnormal Kolbe reaction (Hofer-Moest reaction). Work-up under the usual conditions provided the 2-oxabicyclo[2.2.1]heptane (48) in 83% yield. Treatment of this compound in turn with perchloric acid effected hydrolysis of the ketal with formation of the trisubstituted cyclopentane (49) in nearly quantitative yield (Scheme 11). Cyclopentanes available from this route constitute useful... 

The use of 4-bromo-3-formylthiophene (175) led to the third classical thieno[3,4-6]thiophene (8) via analogous reactions. The aldehyde (175) was protected by ketalization, and then subjected to bromine-metal exchange with n-butyllithium to give a lithio derivative which was reacted with sulfur, followed by methyl chloroacetate. The resulting ester-aldehyde derivative (176a) was condensed under the influence of base to give, after decarboxylation, thieno[3,4-6]thiophene (8 Scheme 61) <76AHC(19)123). 

The above mentioned isomerization of CCCLI to CCCLII constitutes a route from the 9/3,19-cyclosteroids to a new skeletal type which is characteristic of a small group of Buxus alkaloids and will be dealt with in the subsequent text. Another reaction applied to an analogous structural type and leading to cleavage of the cyclopropane ring was reported by Kupchan and Abushanab 219) who had subjected 9, 19-cyclo-5a-pregnane-3,l 1,20-trione-3,2()-diethylene ketal to Wolff-Kishner reduction and obtained a mixture of 10-epimeric ketals CCCLX and CCCLXI. 

Optically active 2-substituted- 1,3-propanediol derivatives were prepared as shown in equation 45. The bis-trimethylsilylated 1,3-diols were condensed with /-menthone in the presence of trimethylsilyl triflate to give the corresponding diastereomeric ketals, which were separated and subjected to further transformations. For example, the cleavage was carried out via a Mukaiyama reaction to generate the a-alkoxy ketone, which could be protected and then cleaved to the optically active, unsymmetrical, monoprotected 1,3-diol52. 

Best and Wege59have reported the first total synthesis of Mansonone F and this is described in Scheme 10. Phenol (111)60 was made to react with 2-chloroacetyl-5-methylfuran (112) in dimethylsulfoxide and sodium methoxide to yield (113). Ketalization of (113) followed by catalytic reduction and basic hydrolysis afforded anthranilic acid (114). Diazotization followed by pyrolysis with propene oxide in 1,2-dichloroethane probably yielded aryne (115), which undergoes intramolecular Diels-Alder reaction producing the adduct (116). Deoxygenation and then acid hydrolysis afforded the product (117). This was subjected to Grignard reaction. The resulting tertiary alcohol on nitration yielded the nitro compound (118) which was subjected to reduction and oxidation respectively to obtain (119). It yielded Mansonone F (120) on dehydration. 

A related reaction type is the high pressure (6.2 kbar) Diels-Alder reaction of 2-pyrones with cyclopropenone ketals 16 to give isolable bicycloadducts 17, which then undergo cycloreversion, electrocyclic rearrangement, and ketal hydrolysis leading to tropones. Tropolones also have been formed in this way. This tropolone annulation chemistry was the partial subject of a review in 1990, and it was exploited in the syntheses of some naturally occurring tropoloisoquinolines 18-20. ... 

An electrochemical oxidative decarboxylation in combination with an ester enolate Claisen rearrangement was reported by Wuts et al. (Scheme 5.2.26) [51]. A variety of allylic esters such as 97 was subjected to an Ireland-Qaisen rearrangement, and the resulting acids (98) obtained were submitted to electrolytic decarboxylation in a divided cell to afford ketals 99. The use of the divided cell was necessary to suppress side reactions such as alkene reduction. 

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