Enolate trapping with

Scheme 2.28 Functionalized allenes obtained by 1,6-cuprate addition to acceptor-substituted enynes and regioselective enolate trapping with methyl triflate (77), aldehydes (78, 79), ketones (80) and silyl halides (81).

Use of TMSCl in combination with HMPA, DMAP, or TMEDA all favored 1,2-addition over 1,4-addition. Sequential a-alkoxyalkylcuprate conjugate addition, enolate trapping with TMSCl, and silyl enol ether alkylation provides a one-pot synthesis of tetrahydrofurans (Scheme 3.35) [129]. Cyclic enones afford as-fused tetrahydrofurans, while acyclic systems give complex mixtures of diastereomers. a-Alkoxyalkylcopper reagents also participate in allylic substitution reactions with ammonium salts [127]. 

IS-Addition to a vinylcyclopropyl ketone22 Concluding steps in a recent synthesis of ( + )-modhephene (3) required the introduction of a methyl group by a novel 1,5-addition of (CH3)2CuLi to the vinylcyclopropyl ketone (1) to afford 2 after in situ enolate trapping with N,N-dimethylphosphoramidic dichloride.24 The synthesis of 3 was completed by reduction of the phosphordiamidate group and hydrogenation. 

Addition of BuiSnLi to cyclohex-2-enone followed by enolate trapping with n-decyl iodide proceeded with high diastereoselectivity to provide the 2,3-rrdiR5-stannyl ketone (16), which could be equilibrated with the cis diastereomer (17) upon treatment with base. LAH reduction, followed by separation of the diasteteomers, afforded samples of the 2-alkyl-3-stannylcyclohexanols as shown in Scheme 17. Iodine(III)-mediated fragmentation was shown to proceed in a stereospecific anti manner, with either of the rrdiRr-2,3-cyclohexanols affording ( )-enal (18), and the cir-2,3-alcohol the (Z)-enal (19 Scheme 17). Enal (18) was then utilized in a stereoselective synthesis of the mosquito pheromone, erythro-6-asx-toxyhexadiecan-S-olide (20 Scheme 18). ... 

The most predictable results are obtained with conformation-ally rigid systems, such as those represented in eqs 5 and 6, which possess axially oriented a-protons. This minimizes complications resulting from the presence of diastereotopic a-protons, although unexpected modes of deprotonation have been described with related chiral amides, which may involve boat conformations. To prevent enolate equilibration (with the resulting loss of stereoselectivity), Corey s internal quench method for enolate trapping with silyl chlorides is frequently used. The stereospecificity of this deprotonation is highly dependent on solvent and temperature conditions. Best results are obtained at —100 °C or lower temperatures, with THF as the solvent. 

The Ireland-Claisen rearrangement via enolate trapping with TBDMS-Cl gave a substantial amount of C-silylated product, thus presenting a technical difficulty in isolating the desired product and causing a low overall yield,... 

The difficultly accessible trans-syn-trans arrangement of the a-b-c ring system present in steroidal antibiotics has now been synthesized. The known enedione (39) was converted into a 6 1 mixture of the desired compound (40) and its isomer (41) by ketalization of the saturated carbonyl, followed by lithium-ammonia reduction and enolate trapping with methyl iodide. After separation, (40) was converted into the tricyclic enedione (42) by standard procedures. The transfused AB-system was then obtained by ketalization, peracid treatment, and boron trifluoride rearrangement of the resulting epoxide to the keto-diketal (43). Removal of the 6-keto-group was performed under mild conditions by a new... 

Alexakis also studied the enantioselective domino reactions catalyzed by a Cu complex of phosphoramidite 28. The 1,4-addition products of this reaction can be employed in an enolate trapping with vinyl oxiran 40 with Pd(0) catalysis (Scheme 11.9) [18]. This domino process afforded the known precursor 43 in the synthesis of the anticancer agent clavularin B (44) [19]. 

TBDMS Enol Ethers. Enolates trapped with TBDMSCl to prepare the corresponding enol ethers are more stable than the corresponding TMS enol ethers. The potassium enolate of 2-methylcyclohexanone, prepared by addition of potassium hydride to a solution of the ketone and TBDMSCl in THF at —78 °C followed by warming to rt, gave the thermodynamic enol ether in a 56 44 ratio. In the presence of HMPA, the ratio improves to 98 2 (eq 6). This method works especially well with ketones with a propensity for self-condensation. ... 

Scheme 53 Tandem copper-NHC-catalysed ECA of Grignard reagents to a-substituted cyclic enone/enolate trapping with 31 by Alexakis [88]...

In the late 1970s, Enders pioneered an elegant method for ketone and aldehyde alkylation involving the use of metalated chiral hydrazones [92, 93). Extensive studies with the (S)-l-amino-2-methoxymethylpyrrolidine (SAMP, 150, Scheme 3.24) auxiliary and its enantiomer RAMP established these as superb chiral auxiliaries with numerous applications. In a typical alkylation sequence, a RAMP/SAMP hydrazine is condensed with an aldehyde or a ketone to form the corresponding hydrazone, such as 152. This can subsequently be deprotonated and the resulting enolate trapped with a variety of electrophilic reagents including alkyl halides, aldehydes, Michael acceptors, silyl triflates, and disulfides. The RAMP/SAMP hydrazine auxiliary may be removed by acidic hydrolysis or ozonolysis to reveal the alkylated... 

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