BF3»OEt2 catalysis

Nitriles can act as nitrogen nucleophiles in aziridine ring-opening reactions. Two examples are shown in Scheme 25 in which a formal [3-1-2] cycloadduct is the final product. Tosylaziridine 147 was reacted with benzoni-trile and BF3 OEt2 catalysis to produce the r-fused imidazoline 148 <2004TL1137>. The utility of the reaction is limited in the case of cyclic aziridines to benzofused aziridines and either aryl or benzyl nitriles. It was also found that the reaction required stoichiometric BF3. Lesser amounts of Lewis acid reduced the chemical yield drastically. 

Double asymmetric reactions between [7-(alkoxy)allyl]stannanes 230 and the a-benzyloxy aldehyde 55 exhibited clear matched and mismatched behavior [168]. With BF3 OEt2 catalysis, the matched double asymmetric reaction between (R)-230a and aldehyde (S)-55 generates exclusively the syn,anti adduct 425 (Eq. (11.40)). Formation of 425 can be rationalized through either the antiperipla-nar, Felkin transition state 426 (as proposed by Marshall) or the synclinal Felkin transition state 427. 

In further studies by Larson and Danishefsky it was shown that boron trifluoride etherate (BF3-OEt2) also catalyzes the reaction but with a dramatically different stereochemical outcome. When ZnCh is used as a catalyst the reaction between benzaldehyde and diene (14) gives predominately the cis dihydro-pyrone (16). Under BF3-OEt2 catalysis, however, the trans dihydropyrone (17) is the major product (Table 4). 

Initial investigations of chiral aldehydes by Danishefsky - demonstrated that both ZnCh and BF3-OEt2 exhibited high Cram, Felkin-Ahn (CF) - stereoselectivity. The cyclocondensation reaction of diene (14) with aldehyde (18) (2-phenylpropanal) under BF3-OEt2 catalysis was found to give a 4.3 1 mixture of the trans-CF dihydropyrone (19) and the cis-CF dihydropyrone (20). Only traces of anti Cram-Felkin (ACF) products are isolated. Under ZnCh catalysis, however, an 8 1 mixture of the cis-CF product (20) and the ci s-ACF product (21) is obtained (Scheme 4). A detailed analysis of these stereochemical issues is given later in Section 2.5.3.1. 

In the synthesis of zincophorin, two cyclocondensation reactions are also used. In the first cyclocondensation reaction, trimethylsilyloxy diene (14) reacts with aldehyde (193) using anhydrous MgBr2 as the catalyst to give the anti-ACF pyrone (194) in 80% yield (Scheme 53). The syn.anti ratio in this reaction is 7 1. After a series of standard manipulations aldehyde (19< ) is obtained. In the second cyclocondensation reaction, anti-CF pyrone (197) results from reaction of the (4 )-r-butyidimethylsilyloxy diene (195) with aldehyde (19< ) under BF3-OEt2 catalysis (197) and its syn-CF isomers are obtained in a ratio of 4 1 and overall yield of 68%. The anti-CF aldol product is purified and cyclized to anti-CF pyrone (197) in benzene using pyridinium p-toluenesulfonate as a catalyst. Pyrone (197) converted into zincophorin (198) by a sequence of steps shown in Scheme 52. 

More recently, Lewis acids have found use in the allylboration of aldehydes [62-64]. In these new conditions, the Lewis acid activates the reaction by rendering the boron atom in the allylboron reagent more electrophilic [65], thus allowing reactions to take place at significantly lower temperatures. A recent example is Kabalka and coworkers use of BF3 OEt2 catalysis to form highly functionalized homoallylic alcohols (Equation 63) [66]. 

Palenzuela and coworkers explored the reaction of vinyl allenes with imines under the influence of Lewis acids, and found that reacting the trisubstituted allene (119) with N-benzyl amine under BF3 OEt2 catalysis provides the octahydroquinoline derivative (120) as a single isomer (Equation 73) [76]. 

Sames and coworkers have very recently introduced BF3 OEt2 catalysis to promote room temperature hydroalkylation of electron deflcient olefins as a formal sp C-H functionalization process. Coordination of the Lewis acid to the alkene moiety of the tetrahydropyran (121) facilitates a 1,5-hydride shift to afford a zwitterionic species, (122), which is followed by nucleophilic attack at the oxocarbonium center to furnish the requisite spirocyclic pyran (123) (Equation 74) [77]. 

Glycosylation utilizing glycosyl fluorides in the presence of BF3 OEt2 was reported concurrently by Ishido, Voznij, Nicolaou, and their respective coworkers, and Kunz and Sagar. Ishido and coworkers prepared 1 — 1 a,a and y ,/ )-disaccharides under BFj catalysis by condensation of... 

As demonstrated with acetals and ketals, aminals are also readily reduced with silanes under acid catalysis. The Et3SiH/BF3 OEt2 combination reduces... 

Resin-bound diols, amino alcohols, and dithiols, which reversibly form cyclic acetals with aldehydes and ketones, have been successfully used as linkers for carbonyl compounds (Entries 5-11, Table 3.40). Acetal formation on insoluble supports can be achieved by azeotropic removal of water (C6H6, TsOH, reflux [720]), whereas dithio-acetals can be prepared by acid-catalysis alone (BF3 OEt2 or TMSC1 CHCI3,0 °C, 2 h [721]). /V-Acylaminals such as R-CFI(OMe)NFI-CO-Pol have been prepared by treatment of resin-bound amides H2NCO-Pol with aldehydes in the presence of HC(OMe)3 and TFA [722],... 

Alkenylsilanes and -stannanes, and arylsilanes and -stannanes are useful reagents for transfer of an sp -carbon unit to electrophiles under titanium catalysis. Epoxides are opened by TiCE to generate cationic carbon, which is successfully trapped with bis(trimethylsilyl)propene as an aUcenylsilane (Eq. 122) [305]. Other Lewis acids, for example ZnCla, SnCU, and BF3 OEt2, proved less satisfactory. Cyclic epoxides such as cyclopentene and cyclohexene oxides gave poorer yields. An intramolecular version of this reaction proceeded differently (Eq. 123) [305]. Eqs (124) and (125) illustrate diastereoselective alkenylation and arylation of (A,0)-acetals that take advantage of the intramolecular delivery of alkenyl and aryl groups [306], Cyclic ethers... 

The conjugate addition of oxygen nucleophiles to acceptor-substituted olefins is the oxa-Michael reaction (Scheme 15). The term is derived from heteroatom replacement nomenclature, meaning that oxygen takes the place of a CH2 unit (RCH2 RO ). Oxa-Michael reactions have been known for many years and are often catalyzed by bases or acids [7]. Catalysis by metals has been reported sporadically in the older literature, e.g. for the case of alcohol addition to vinyl ketones with a Nieuwland catalyst (HgO, BF3-OEt2, ROH) [75-77]. A patent describes a PdCl2-catalyzed addition of alcohols to acrolein or methacrolein [78]. 

Compared with chiral nonracemic a-amino carbonyl compounds - which are not suitable substrates for MBH reaction, mainly due to their racemization under normal conditions after prolonged exposure times to catalyst or due to poor diastereoselectivity " a-keto lactams, enantiopure 3-oxo-azetidin-2-ones 168, readily react with various activated vinyl systems promoted by DABCO to afford the corresponding optically pure MBH adducts 169 without detectable epimerization (Scheme 1.69). " However, the Lewis acid-mediated reaction of electron-deficient alkynes with azetidine-2,3-diones 168 as an entry to p-halo MBH adduets was not very sueeessful the coupling product 170 was achieved with concomitant acetonide cleavage as a single ( )-isomer in low yield, in the presence of trimethylsilyl iodide under BF3 OEt2-induced catalysis (Scheme 1.69). 

---