Homoenolate additions

Concurrently, Glorius and co-workers reported the synthesis of y-butyrolactones under similar reaction conditions [122, 123], Glorius has extended this reactivity to include trifluoromethyl ketones (Scheme 36). In addition to intermolecular reactions, intramolecular homoenolate additions are possible in modest yield Eq. 21 [123],... 

Nair and co-workers reported the diastereoselective synthesis of spiro y-butyro-lactones from 1,2-dicarbonyls [125]. The authors studied the reaction with 1,2-cyclohexane dione 230 which produces the desired lactone 232 in good yields Eq. 22a. Isatins 233 are more reactive, but the products 235 are obtained as a 1 1 separable mixture of diastereomers Eq. 22b. The Nair research group extended this methodology to include homoenolate addition to tropanone 236 to form bicyclic 5-lactones 238 Eq. 22c [126]. 

In related methodology, Scheldt and co-workers have also reported the homoenolate addition to nitrones to produce products of a formal [3-1-3]. Upon treatment with... 

The ring-opened dipolar intermediate suggests reactivity towards nucleophiles and electrophiles. The latter occurs in the TiCl4 promoted addition of methyl 2-siloxycyclo-propanecarboxylates to carbonyl compounds and to an iminium salt (equation 99). The products of both processes are very versatile intermediates allowing synthesis of different furan derivatives and other compounds Concerning the liberated carbonyl function, both reactions can be classified as homoenolate additions, thus putting further emphasis on the cyclopropane homoalkene equivalence. 

In 2008, the Bode group documented a convenient solution to the synthesis of stereochemically defined tertiary amine derivatives via NHC-catalyzed formal homoenolate additions to ketimines derived from saccharin with low catalyst loading (0.5 mol%). ° This methodology features high activity of the catalyst, cfs-selectivity, and superiority of aprotic solvents. Based on detailed... 

In 2012, Ye, Jiao, and co-workers described the first application of iV-aryl isatin imines as the electrophiles in NHC-catalyzed homoenolate additions, providing a simple and efficient approach to spirocyclic y-lactam oxindoles. Utilizing the catalyst with free hydroxyl group first developed in the Ye group, an asymmetric variant of this reaction was demonstrated in a moderate enantioselective manner (80% yield, 6 1 dr, 74% ee) (Scheme 7.48). 

B. Maji, L. Ji, S. Wang, S. Vedachalam, R. Ganguly, X.-W. Liu, Angew. Chem. Int. Ed. 2012,51, 8276-8280. N-heterocy-clic carbene catalyzed homoenolate-addition reaction of enals and nitroalkenes asymmetric synthesis of 5-carbon-synthon 5-nitroesters. 

Sequential reactions involving metal and NHC catalysis are quite scarce in the literature NHCs are powerful ligands that coordinate many metals, resulting in altered activities for both partners, so it may be difficult to create balanced catalytic systems. Fortunately, the few examples available cover several NHC mechanistic pathways, including the benzoin condensation [104], homoenolate addition [105], and NHC-catalyzed oxidation [106, 107] (Scheme 26.21). 

The scope of this protocol was extended by these authors to homoenolate addition to p,y-unsaturated a-ketoesters, which afforded the corresponding chiral highly substituted and functionalisable cyclopentanols in good yields, moderate to high diastereoselectivities of up to 90% de, and excellent enantioselectivities of up to 98% ee, as shown in Scheme 7.15. ... 

Our proposed mechanistic model for homoenolate addition suggests the existence of a transient enolate after the nucleophilic addition at the gamma position (Scheme 14). We decided to explore the possibility of intercepting the enol and utilize a second electrophile to functionalize the homoenolate at a-position and... 

The NHC generated from its precursor (449) has been reported to catalyse (at 20 mol% loading) the homoenolate addition of enals R CH=CHCH=0 to nitroalkenes R CH=CHN02 in the presence of KHCO3 as a base in a toluene-MeOH 20 1 mixture at room temperature over 24 8 h. The anti-configured 5-nitro esters 02NCH2CH(R )CH(Ri)CH2C02Me thus obtained were of <12 1 dr and <99% ee (Ri = Ar, hetero-Ar, alkyl R = Ar, ArCH=CH, ArC=C).299... 

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