Epoxides, alkylation with

Thus, metalation of 78 and alkylation with epoxide Ej in Et20 or THF likewise furnished the unrearranged carbinols exclusively. Then, addition of ITMPA or DMPU induced the 1,4-Brook isomerization (equation 28) and addition of a second epoxide leads to 79... 

Lithiation of 2-bromo-3,3-disubstituted-methylenecyclopropanes by metal halogen exchange reaction with EtLi in ether, followed by alkylation with epoxides, gave selectively ring-alkylated /8-alcohols, derived from attack at the epoxide primary carbon (equation 299). When R1 R2 a mixture of isomers is obtained369. 

The alkylation of compounds 591 and 592 can be performed with primary alkyl bromides and iodides824,865,866,871 887. This procedure, followed by different transformations of the alkylated products, has been applied extensively in organic synthesis. However, the alkylation with epoxides gave very poor yields with intermediates 591 and 592, so they have to be transmetallated to low-order cuprates 594888 and 595889 in order to undergo reaction with these electrophiles in THF at 0 to 20 °C. 

Cuprates derived from compound 604 and Cul911,912 or from copper acetylide and compound 605913,914 underwent alkylation with epoxides. 

Alkylarsino compounds undergo halogenolysis of the metal-carbon bond as do the bismuth and antimony analogs (Scheme 18). Diphenylarsinomethyllithium can also be alkylated with epoxides. 

A short synthesis of (5 ,9 )-(—)-indolizidine 223AB (1806) by Smith and Kim used the silylated dithiane 1847 as a linchpin for the one-pot tandem alkylation with epoxide (- -)-1848 and the N-tosylaziridine (—)-1849 (Scheme 233). The first intermediate is presumably alkoxide 1850, which undergoes a 1,4-Brook rearrangement to 1851 before reaction with the aziridine. The bis-alkylated dithiane (—)-1852 was isolated in... 

NBP reacts with epoxides according to I to yield methine dyestuffs [14] and with alkylating agents (R-X, X = e.g. halogen) according to II to yield colored pigments [15]. 

Alkylation of enamines with epoxides or acetoxybromoalkanes provided intermediates for cyclic enol ethers (668) and branched chain sugars were obtained by enamine alkylation (669). Sodium enolates of vinylogous amides underwent carbon and nitrogen methylation (570), while vicinal endiamines formed bis-quaternary amonium salts (647). Reactions of enamines with a cyclopropenyl cation gave alkylated imonium products (57/), and 2-benzylidene-3-methylbenzothiazoline was shown to undergo enamine alkylation and acylation (572). A cyclic enamine was alkylated with methylbromoacetate and the product reduced with sodium borohydride to the key intermediate in a synthesis of the quebrachamine skeleton (57i). 

While alkylation of terminal epoxides is reliable, attempted alkylations of 1,2-disubstituted epoxides have proved capricious. An unsuccessful approach to the swinholides, which called for the alkylation of cyanohydrin 47 with epoxide 48, is one such example. In the event, alkylation cleanly produced imidate 49, rather than the expected product 50 [27] (Eq. 14). 

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>. 

We emphasize that the above mechanism is strictly valid only for H202 and alkyl hydroperoxide epoxidations of alkenes catalyzed by TS-1 and Ti-MCM-41. In view of the observation of similar titanium oxo species when H2 + 02 are brought in contact with TS-1 or Ti-MCM-41 (54), similar conclusions may be drawn for that system as well. A radical mechanism involving the Ti=0 groups had been proposed earlier by Khouw et al. (221) for the hydroxylation of alkanes. No spectroscopic investigation of the TS-l/H202/alkane has yet been reported. 

This epoxide to aldehyde rearrangement was postulated to be the first step in the silver-mediated reaction of alkylzirconocene chlorides with epoxides, in which the aldehyde is subsequently alkylated by the alkylzirconocene species (cf. Scheme 8.44) [56], In a control experiment, it was shown that zirconocene dichloride (1 equivalent or less) and silver (catalytic amounts) do indeed induce the rearrangement of an epoxide to an aldehyde very quickly. 

Alkyl azides have been involved in the synthesis of indolizidinone derivatives in several ways. One example (Scheme 7) is the intramolecular Schmidt reaction between alkyl azides and ketones which can be used to transform azidoketone 24 into the corresponding indolizidinones 26 through intermediate 25 <2001JOC886> or with epoxides to obtain the indolizidine 27 <2004JOC3093>. 

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