Silyl nitronates, enantioselective Michael addition

As an extension of this highly enantioselective Michael addition of silyl nitronates with a, p-unsaturated aldehydes, the reactions with cyclic a,p-unsaturated ketones as a Michael acceptor were also tested (Scheme 9.15). Cyclohexenone and cyclohepte-none were employed as a useful Michael acceptor with various silyl nitronates in the presence of catalyst (R,R)-6c, and gave the corresponding enol silyl ethers 28 with excellent stereoselectivities [30]. 

Further applications of the chiral ammonium bifluoride-catalyzed enantioselective Michael addition of silyl nitronates has been shown in the reactions with nitroalkenes as a Michael acceptor (Scheme 9.17). These studies were started by examining the reaction of nitropropane-derived silyl nitronate 23b with P-nitrostyrene, using the chiral quaternary ammonium bifluoride (R,.R)-6d. When P-nitrostyrene was treated with 23b (1.2 equiv.) in the presence of (K,f )-6d (2mol%) in THF at — 78 °C, the... 

Highly enantioselective Michael addition of silyl nitronates (105) to cyclic o /3-unsaturated ketones (106 n = 0-2) has been accomplished by the utilization of N-spiro C2-symmetric chiral quaternary ammonium bifluoride (108) as an organocatalyst, offering a new route to the enol silyl ethers of scalemic y-nitro ketones (107 70-90% ee).156... 

Based on the enantioselective Michael addition/ISOC (intramolecular silyl nitronate olefin cycloaddition)/lragmentation sequence previously developed by the group of Rodriguez [33a], Shao and coworkers proposed an extrapolation for the construction of spirooxindoles catalyzed by a bifunctional tertiary amine-thiourea catalyst XV between 4-allyl-substituted oxindoles 63 and nitrostyrenes 64 (Scheme 10.21) [33b]. After the addition of TMSCl and EtgN at -30 C, the Michael adduct underwent an ISCX3 to afford the spiro oxime derivatives 65 in very good yields (85-85%), and excellent diastereo (up to >30 1) and enantioselectivities (94-99% ee) after the treatment with TBAF. 

The efficient homogeneous catalysis of chiral ammonium bifluorides of type 15 has been further utilized for achieving an asymmetric Michael addition of silyl nitronates to a,/ -unsaturated aldehydes. Here, chiral ammonium bifluoride 15b bearing a 3,5-di-tert-butylphenyl group was found to be the catalyst of choice, and the reaction of 16a with trans-cinnamaldehyde under the influence of (R,R)- 15b (2 mol%) in THF at —78 °C produced the 1,4-addition product 18 predominantly (18/19 = 24 1) as a diastereomeric mixture (syn/anti = 78 22) with 85% ee of the major syn isomer (Scheme 4.9). Further, use of toluene as solvent led to almost exclusive formation of the 1,4-adduct (18/19 = 32 1) with similar diastereoselec-tivity (syn/anti = 81 19), and critical enhancement of the enantioselectivity was attained (97% ee) [15]. 

Maruoka et al. have developed and used A-spiro C2-symmetric chiral quaternary ammonium bifluorides [151] 102, 103, and more recently 104, to promote the regio- and anti-selective Mukaiyama-Michael addition of silyl nitronates to a, 3-unsaturated aldehydes [152], cyclic a,P-unsaturated ketones [153], and nitroalk-enes [154] with good yields and enantioselectivities (Scheme 2.52). Final chiral silyl enol ethers are easily hydrolyzed to the corresponding carbonyl compounds or functionalized at the a-position by reaction with electrophiles. 

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