Cuprate chemistry

Syntheses of diastereomerically pure racemates of himachalene derivatives started from cycloheptanone G (Fig. 9). The sequence to I involved dimethyla-tion to yield H followed by bromination/dehydrobromination and conjugate methylation using cuprate chemistry. The sequence furnishing L and M follows a Robinson-annelation type Reaction of I with 3-(trimethylsilyl)but-3-en-2-one yielded K. Refluxing K with potassium hydroxide in ethanol removed the silyl group and cyclized the diketone to form a 97 3 mixture of racemic L and M. Occurring as a volatile in A.flava, L served as a versatile intermediate in the syntheses of other Aphthona compounds. 

Demonstration of the critical roles of the open conformations of polymetallic clusters highlights theoretical analysis in cuprate chemistry. Polymetallic clusters in various synthetic reactions are currently attracting the attention of synthetic and mechanistic chemists alike [40, 180-183]. 

Relative to tertiary alkyl halides, secondary derivatives react considerably slower. At room temperature and long reaction periods ( 24h) cyclohexyl chloride is almost quantitatively methylated with dimethyltitanium dichloride (prepared in situ from dimethylzinc and catalytic amounts of TiQ4)137>, but other cyclic or acyclic halides tend to undergo competing rearrangements prior to C—C bond formation 77). The same applies to 1,2-dihalides such as 1,2-dibromocyclohexane which affords 1,1-dimethylcyclohexane instead of the 1,2-dimethyl derivative137. In complete contrast, activated secondary chlorides behave much like tertiary derivatives, i.e., methylation is fast and position specific at low temperatures. Examples are shown in Equation 86137>. It should be noted that in such cases cuprate chemistry affords less than 40 % of methylation products138). 

Similar C-glycosidations are available via cuprate chemistry. For example, as shown in Scheme 2.3.2, Bihovsky, etal.,24 utilized a variety of cuprates in the preparation of a-C-methylglycosides. The yields were relatively poor when acetate protecting groups were used. However, substantial improvements in the yields were observed with methyl and benzyl protecting groups. In all cases, the a anomer was favored in ratios as high as 20 1. 

In an earlier example of the applicability of cuprate chemistry to C-glycosidations, Bellosta, et ai.,26 stereospecifically prepared epoxides from protected glucals (Scheme 2.3.4). Unfortunately, as shown in the previous example, the use of acetate protecting groups instead of benzyl protecting... 

Another pair of stereochemically complementary routes to mid-chain vinylsilanes starts from the allylic alcohol (76) made by combining the a-trimethylsilylvinyllithium reagent with the appropriate aldehyde. Cuprate chemistry allows the other chain to be attached with either stereochemical outcome (Scheme 92) and the route is also amenable to the synthesis of tetrasubstituted vinylsilanes, simply by starting with a ketone in place of the aldehyde. ... 

Additional metals that have been used in novel, direct metalation reactirais of indole include aluminum [283, 284], copper [285], and zinc [220]. To compare the different conditions that have been explored, different syntheses of N-(tert-butoxycarbonyl)-2-iodoindole (48b) are compared below (Table 12). From 4, 48b was prepared using different direct metalation methods followed by quenching with iodine the highest yielding conditimis involved the cupration chemistry. 

Reaction with Alkynes. The silyl cuprate reacts with alkynes by syn stereospecific metallo-metallation (eq 3). Provided that the cuprate is derived from copper cyanide, the regioselectivity with terminal alkynes is highly in favor of the isomer with the sUyl group on the terminus. The intermediate vinyl cuprate (3) reacts with many substrates, familiar in carbon-based cuprate chemistry, to give overall syn addition of a silyl group and an electrophile to the alkyne. A curious feature of this reaction is that the intermediate (3), although uncharacterized, has the stoichiometry of a mixed silicon-carbon cuprate, and yet it transfers the carbon-based group to most substrates, in contrast to the behavior of mixed silyl alkyl cuprates. 

The sequence produces a mixture of four oiefin geometricai isomers in nearly equai amounts (one of which is CJH). Thus, the cuprate chemistry is not stereoseiective. 

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