Epoxide opening amine, cyclization

The asymmetric lithiation/substitution of Af-Boc-Af-(3-chloropropyl)-2-alkenylamines 395 by w-BuLi/(—)-sparteine (11) provides (5 )-Af-Boc-2-(alken-l-yl)pyrrolidines 397 via the allyllithium-sparteine complexes 396 (equation 106) . Similarly, the piperidine corresponding to 397 was obtained from the Af-(4-chlorobutyl)amine. Intramolecular epoxide openings gave rise to enantioenriched pyrrolidinols. Beak and coworkers conclude from further experiments that an asymmetric deprotonation takes place, but it is followed by a rapid epimerization a kinetic resolution in favour of the observed stereoisomer concludes the cyclization step. 

The use of a cationic aza-Cope rearrangement in concert with a Mannich cyclization has also been applied to the total synthesis of enantiomerically pure (—)-crinine (359) (205). In the event, nucleophilic opening of cyclopentenoxide with the aluminum amide that was formed on reaction of (/ )-a-methylbenzyl-amine and trimethylaluminum gave the amino alcohol 485 together with its (15,25) diastereomer. Although there was essentially no asymmetric induction in this process, the diastereomeric amino alcohols were readily separated by chromatography, and the overall procedure therefore constitutes an efficient means for the preparation of enantiomerically pure 2-amino alcohols from epoxides. When the hydrochloride salt derived from 485 was treated with paraformaldehyde and potassium cyanide, the amino nitrile 486 was formed. Subsequent Swem oxida-... 

The method employed by Law, et al. to obtain Ad-disubstituted ISQs [87] was a modification of the approaches of Henbest [88], Huffman [89] and Nelson [90] (Scheme 8). Epoxidation of commercially available methyl-3-cyclohexene-1-carboxylate (80) with m-CPBA yielded a mixture of epoxides (81a and 81b), which were then opened with various amines producing the isomeric amino alcohols (82a and 82b). Only isomer 82a is capable of undergoing cyclization to the... 

The conversion of epoxides to aziridines by nucleophilic ring-opening with azide ion or amines followed by cyclization was covered in Section 1.01.9.3. The conversion of azirines to aziridines by nucleophilic addition and the conversion of aziridines to azirines by elimination were covered in Sections 1.01.6 and 1.01.7, respectively. 

Electrooxidations can also make use of mediators In this case they proceed at lower potentials and need milder conditions . Enamines derived from aldehydes and bearing a )5-hydrogen atom were oxidized, using KI as a mediator, into the corresponding -keto amines. In the mechanism proposed, an unknown active species, T is assumed to be formed by oxidation of 1 and to add to the double bond. The resulting iodohydrin cyclized into an a-amino epoxide and subsequently is ring opened into a jS-ketoamine, by a 1,2-hydrogen shift (Scheme 81). 

Cyclization by Displacement of Leaving Groups in Carbohydrate Substrates by Amines. The synthesis of l,2,4-trideoxy-l,4-imino-D-erythro-pentitol (31) has been achieved in eight steps, in 42% overall yield, from 2,5-di-O-p-tol-uenesulfonyl-D-ribono-1,4-lactone according to Scheme 7. The correct stereochemistry in the product was achieved by epimerization at C-4 in a 5-0-tosylated 2-deoxy lactone intermediate base action on the lactone produced a 4,5-epoxide of an open-chain carboxylate derivative which subsequently ring-closed by intramolecular attack of the carboxylate anion on the epoxide to produce the diastereomeric lactone. ... 

Construction of the Dolby model system began with epoxidation of cyclohexene 209 employing mCPBA in chloroform. The epoxide product was then subjected to a base-promoted cyclization via amide deprotonation and oxirane opening to provide benzamide 210 (Scheme 23). Hydroxyl oxidation using the Jones conditions next furnished cyclohexanone 211. A Fischer indole synthesis on this scaffold, followed by amine deprotection using sodium hydroxide, led to the desired l,3-(iminoethano)carbazole 83. While the yield of this route was low, it was the first example of a method to fashion the 2-azabicyclo[3.3.1]nonan-8-one system 211, and importantly demonstrated that indoHzation on such a scaffold was possible. 

Pyne et al. were the first to use RCM in the synthesis of a tetrahydropyrrolizidine, namely, 1-epi-australine 93. Ring opening of epoxide 97, readily obtained from 3-butynol, with an enantiopure allyhc amine provided the desired diallylamine in moderate selectivity (Scheme 2.23). Conversion of the diallylamine into oxazolidi-none 98 opened the door to the first RCM cyclization. Portionwise addition of [Ru]-I catalyst (30mol% in total) gave product 95 in 97% yield. When less catalyst was used, significantly lower yields of 95 were obtained. syn-Dihydroxylation of the 3-pyrroHne 95 and an additional five more steps were required to obtain (+)-l-epi-australine (93) as a colorless oil. 

---