Alkylative ring opening

Certain P-stereogenic diphosphines have recently provided outstanding results in this transformation, giving exclusively the syn diastereomers of 51 in high enantioselectivities. Some selected results, reported by Imamoto and coworkers,are collected in Table 8.8. 

The electron-rich t-Bu-MiniPHOS ligand provided good yield but moderate enantioselectivity (entry 1). Much better results have been obtained with the related ligand t-Bu-BisP (entry 2) and with the QuinoxP ligands (entries 3-5). The diphosphine of entries 6 and 7, containing an unsubstituted ethynyl group, leads to excellent yields and almost perfect enantioselectivities. 

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More traditional carbon nucleophiles can also be used for an alkylative ring-opening strategy, as exemplified by the titanium tetrachloride promoted reaction of trimethylsilyl enol ethers (82) with ethylene oxide, a protocol which provides aldol products (84) in moderate to good yields <00TL763>. While typical lithium enolates of esters and ketones do not react directly with epoxides, aluminum ester enolates (e.g., 86) can be used quite effectively. This methodology is the subject of a recent review <00T1149>. 

Enantioselective alkylative ring opening of these oxabicyclic alkenes has also been studied. Lautens and coworkers discovered that palladium complexes efficiently catalyze the addition of organozinc reagents to these activated alkenes with concomitant ring opening. In the presence of (Tol-BINAP)PdCl2, diethylzinc adds to oxabenzonor-... 

Feringa and coworkers have developed a copper phosphoramidite catalyst system that accesses the diastereomeric anti products in the alkylative ring opening... 

Tautens has extended this chemistry to include the alkylative ring opening of these systems using aryl and vinyl boronic acids as nucleophiles in the presence... 

Compared to oxabenzonorbomenes, oxabicyclo[2.2.1]heptenes or oxabicyclo[3.2.1] octenes are less reactive substrates, and the Pd-catalyzed alkylative ring-opening process with organozinc reagents generally required heating in 1,2-dichloroethane at reflux. The addition of Zn(OTf)2 dramatically improved the rate of the reaction which could be carried out in CH2C12 at room temperature, as illustrated for the conversion of 83 to the... 

An attractive alternative strategy Scheme 3.20) for the synthesis of (88b) focused on the conversion of a 3-formylthietane acetal (99) to an unsymmetri-cally substituted isobutyraldehyde acetal (100) via alkylative ring opening with p-methoxybenzyl bromide. Several subsequent steps produced a mixture of (101) and (102) which could not be fully aromatized to (102) owing to extraordinary insolubility, which, unfortunately, ultimately precluded synthesis of (88b) by this route. 

The anti -stereocontrolled alkylative ring-opening reaction of azabicyclic alkenes has been reported.100 iV-(2-Pyridyl)sulfonylazabenzonorbornadiene (36) has reacted with Grignard reagents in the presence of catalytic amounts of CuCN to afford, in good yields and excellent anti selectivity, the corresponding dihydronaphthalene-1-amines (37) (Scheme 20). 

Copper-catalyzed enantioselective allylic alkylation ring-opening reactions of oxiranes (and aziridines) with alkyl metals (e.g., dialkylzincs) has been reviewed by Pineschi <2004NJC657>. 

Table 11 Alkylative ring opening of oyolopentene and oyolohexene oxides...

Table 12 Asymmetric alkylative ring opening of epoxides of oxacycies...

With fluoride ion under aprotic conditions alkylating ring-opening can be performed (equation 94). Similarly, a clever [3 -I- 2] annulation combines a fluoride-induced Michael addition to vinyl phosphonium salts with a subsequent internal Wittig reaction (equation 95) . ... 

Transition Metal-Catalyzed Alkylative Ring-Opening... 

M. L. Lautens,J. L. Reneaud, andS. Hiebert, Palladium-catalyzedenantioselective alkylative ring opening, J. Am. Chem. Soc., 122 (2000) 1804-1805. 

H-4,7 - Indazoledione, 4,7-dihydro-3-vinyl-synthesis, 1, 279 Indazole-l-lsN synthesis, 5, 291 Indazole-2-lsN synthesis, 5, 291 Indazoles acidity, 5, 224 N-l -alkylated ring opening, 5, 219 alkylation, S, 228, 230 amination, S, 55, 234 anions... 

Cyclic /neso-epoxides, such as cyclopentene oxide (64), can be induced to undergo alkylative ring-opening in the presence of trialkylaluminum reagents under catalysis using N-heterocyclic carbenes (62). These unusual catalysts are derived from the deprotonation of imidazolinium salts (61), and serve as phosphine mimics in terms of electron-pair donation behavior to form aluminum complexes of the type 63 <01 OL2229>. 

Scheme 4.14 Synthesis of 1,4-benzodiazepines through domino N-alkylation/ring open-...

P-t rt-Aminocarbonyl compds. from N-subst. isoxazolidines N-Alkylative ring opening... 

Alkylative ring opening is a palladium-catalysed C-C bond-forming reaction in which a dialkylzinc reagent opens a heterocycle, with the formation of two stereogenic centres. The model substrate is oxabenzonorbornadiene (50, Scheme 8.22). 

Table 8.8 Results of Pd-catalysed alkylative ring opening of 50 (Scheme 8.22).

Zhang L, Le CM, Lautens M (2014) The Use of silyl ketene acetals and tmol ethers in the catalytic enantioselective alkylative ring opening of oxa/aza bicyclic alkenes. Angew Chem... 

Lautens M, Renaud JL, Hiebert S (2000) Palladium-catalyzed enantioselective alkylative ring opening. J Am Chem Soc 122 1804—1805... 

Fischer indole synthesis, 91-95 Formamidine disulfide, salts of, 281, 282 Formazans, oxidation of, 37 Furans, alkyl-, ring-opening of, 63... 

Chiral alcohol (15,2/ )-52 (90-94% ee) was obtained as a major product by the chiral copper phosphoramidite-cata-lyzed alkylative ring opening of oxabenzonorbornadiene with diethylzinc. The esterification of alcohol (lS,2/ )-52 with (-)-CSDP acid yielded ester (15, 2/ )-(—)-53, which was recrystallized giving single crystals suitable for X-ray crystallography. The AC of (—)-53 was unambiguously determined based on the known AC of the CSDP acid moiety. 

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