BF3-Promoted Reactions

In some cases an intermediate bicyclic difluoroboron enolate such as 1 can be solated from the BF3-promoted reaction and converted into a bicyclic ketone (equation II). 

The BF3-promoted reaction of aldehydes or acetals, methyl carbamate, and homochiral crotylsilanes is valuable for highly diastereo- and enantioselective synthesis of homoallylamines (Scheme 10.147) [419]. Interestingly, reaction using aromatic aldehydes or their acetals at low temperature forms stereo-controlled functionahzed pyrrolidines predominantly by a formal [3-1-2] cycloaddition (Section 10.3.3.1). 

BF3 promoted reactions. Keck also pointed out that the preferred transition state probably varies from one case to another owing to subtle changes in non-bonding interactions, a conclusion supported by computational studies performed with the analogous allylsilanes. 

The Friedel-Crafts reaction is a very important method for introducing alkyl substituents on an aromatic ring. It involves generation of a carbocation or related electrophilic species. The most common method of generating these electrophiles involves reaction between an alkyl halide and a Lewis acid. The usual Friedel-Crafts catalyst for preparative work is AICI3, but other Lewis acids such as SbFj, TiC, SnCl4, and BF3 can also promote reaction. Alternative routes to alkylating ecies include protonation of alcohols and alkenes. 

Nitrile oxides are widely used as dipoles in cycloaddition reactions for the synthesis of various heterocyclic rings. In order to promote reactions between nitrile oxides and less reactive carbon nucleophiles, Auricchio and coworkers studied the reactivity of nitrile oxides towards Lewis acids. They observed that, in the presence of gaseous BF3, nitrile oxides gave complexes in which the electrophilicity of the carbon atom was so enhanced that it could react with aromatic systems, stereoselectively yielding aryl oximes 65 and 66 (Scheme 35). ... 

EtjN,663 and N,N -carbonyldiimidazole (100).664 In the latter case easily alcoholyzed im-idazolides (101) are intermediates. BF3 promotes the esterification by converting the acid to RCO+ BF3OH, so the reaction proceeds by an AacI type of mechanism. The use of BF etherate is simple and gives high yields.665 Carboxylic esters can also be prepared by treating carboxylic acids with /-butyl ethers and acid catalysts.666... 

Other alkyl hypohalites usually add to carbon-carbon multiple bonds in a free-radical process.155-158 Ionic additions may be promoted by oxygen, BF3, or B(OMe)3.156-160 While the BF3-catalyzed reaction of alkyl hypochlorites and hypo-bromites gives mainly halofluorides,159 haloethers are formed in good yields but nonstereoselectively under other ionic conditions.156-158 160 In contrast, tert-BuOI reacts with alkenes in the presence of a catalytic amount of BF3 to produce 2-iodoethers.161 Since the addition is stereoselective, this suggests the participation of a symmetric iodonium ion intermediate without the involvement of carbocationic intermediates. 

When chiral allylsilanes are used for coupling with aldehydes, the diastereoselectivity of the reaction depends on the nature of the Lewis acid employed. Chelative SnCU-promoted reaction gives 212 whereas BF3 OEt2 catalyzes the annulation reactions leading to 213 (equation 174)315-317. 

The BF3-promoted rearrangement of several 4,5-epoxy-9-trimethylsilyldecalines having different relative stereochemistry and substitution at the oxirane ring is described. The presence of the silicon at C(9) favours two different main reaction pathways... 

The BF3-OEt2-promoted reaction of a-enones with diallylsilanes forms double allylation products (Equation (35)).145 The tandem allylation can be rationalized by intramolecular allylation of the /3-silylcarbenium... 

The [2 + 2]-cycloaddition of allylsilanes is applicable to the synthesis of substituted oxetanes from aldehydes and ketoesters (Equation (49)).176,193 The BF3-OEt2-promoted reaction of iV-tosylaldimines with allylsilanes gives [3 + 2]-cycloadducts, 3-silylpyrrolidines (vide supra).178 In contrast, iV-acylaldimines are converted into [2 + 21-cycloadducts under similar conditions.194... 

A few of these reactions demand special comment. Dimethyl-formamide must act as a nucleophile in attacking an epoxide/ BF3 complex to give the ion (7), which suffers hydrolysis in water to give the 6j5-formate [152]. Boron trifiuoride and triethyl aluminium, both efficient Lewis acids, are able to promote reactions with substances which are only very weak proton acids e.g, alcohols and HCN). This may be due to... 

Comparison of reaction rates and selectivities for BF3-promoted additions of crotyl tributylstannanes to aldehydes revealed that the trans crotyl isomer reacts faster and is more yn-selective than the cis isomer (Table 8) [18]. It is proposed that the synclinal transition state arrangement for the frans-crotylstannane is stabilized by a favorable interaction between the LUMO of the carbonyl oxygen and the allylic tin sigma HOMO. The analogous transition state for addition of the dx-crotylstannane is destabilized by unfavorable steric interactions (Fig. 3). 

An additional type of orthoester was reported by Kunz [513]. Specifically, the oximate orthoester 233 reacted in BF3-Et20-promoted reactions to give fm/i5 -glycosides. 

Glycosyl 6>-xanthates 247, activated with BF3-Et20, have been reported by Pougny [528]. Similarly, glycosyl carbamates 248 also provided glycosides in BF3-Et20-promoted reactions [529]. 

The mechanistic aspects of this Lewis acid promoted reaction have been examined by low temperature NMR studies, and reaction of the lithium alkynides with the Lewis acid activated epoxides is indicated. The order of the addition of the reagents does not affect the product yields provided that the reaction is carried out at -78 C addition of BF3-OEt2 to a mixture of an epoxide and an alkynide or addition of an epoxide to a mixture of an alkynide and BF3-OEt2 are both possible. The transmetalation between RLi and BF3 which produces unreactive organoboron compounds is shown to be very slow at this temperature. - ... 

Problem 6.14. Draw a mechanism for the BF3-promoted aldol reaction of (CO)5Cr=C(CH3)OMe and PhCHO. 

The Lewis acid-promoted reaction of chiral y -methyl ( )-2-butenylsilane (5)-43 with a-(benzyloxy)propanal affords homoallylic alcohols favoring the anti or syn diastereomers depending on the Lewis acid employed (Scheme 10-17) [36]. The BF3 0Et2-promoted reaction provided a 6.5/1 (44/45) ratio of the syn to anti diastereomers presumably through the antiperiplanar transition structure shown below. When MgBr2 was employed, the anti homoallylic alcohol was favored by a 12/1 (45/44) ratio. A synclinal transition structure accounts for the reversal in selectivity observed with the bivalent Lewis acid. 

The Lewis acid-promoted reaction of the allylsilane (R)-43 with either of the (5)-a-alkoxy aldehydes provides some surprising insights (Scheme I0-19) [34]. The BF3-OEt2-promoted reaction of the silane (R)-43 and either (S)-26 or (S)-46 afforded predominantly the syn homoallylic alcohols 50 and 51, even though this is presumed to be a mismatched combination of reagents. The TiCL-promoted reaction of ( )-43 with (5)-26 or (S )-46 also produces the syn homoallylic alcohols, presumably through a Cram chelate transition structure model (albeit with lesser selectivity for 46). These experiments indicate that the chirality of the R-silane re-... 

In a direct comparison, the CAB catalyst proved to be superior to the titanium binol catalyst in the reaction of branched aldehydes in both reaction times and selectivity. Finally, the CAB-promoted reaction of a chiral aldehyde with ( )-85 was examined (Scheme 10-48). When the aldehyde (7 )-106 reacts with the 2-bute-nylstannane in the presence of the CAB catalyst, a 98/2 mixture of diastereomers is obtained. The CAB-promoted reaction of the aldehyde (S)-106 with the (E)-85 affords a 90/10 mixture of diastereomers. This adduct is the minor isomer from the BF3-promoted addition of ( )-85 to aldehyde (S)-106. Thus, the CAB-promoted additions are strongly reagent controlled, essentially overriding the intrinsic facial preference of the aldehyde substrate. 

The BF3-OEt2-promoted reaction of the enantiomerically enriched MOM-pro-tected alkoxystannane (S)-150 with the aldehyde (5)-26 (mismatched series) affords a mixture of syn and anti homoallylic alcohols 152 and 153 (Scheme 10-65) [103]. The matched series gives much higher selectivity for the syn homoallylic alcohol. Reaction of the TBS-protected alkoxystannane (Sl-lSl with the aldehyde (S)-26 provided the syn homoallylic alcohol 154 and a cyclopropane derivative (not shown). When the bivalent Lewis acid MgBr2 was employed, the stereochemical outcome of the reaction was significantly altered. The anti homoallylic alcohol 156 was favored with the MOM-protected alkoxystannane, while the syn homoallylic alcohol 159 was the only product observed with the TBS-protected alkoxystannane. Antiperiplanar transition structures are proposed to account for the observed selectivity in these reactions. 

Denmark studied the intramolecular allylation reaction of allylstannane 15 in order to differentiate between the syn and anti S g transition states (only anti S h is shown below) as well as to differentiate between the synclinal and antiperiplanar transition states 19 and 20, which are analogous to transition states 11 and 14, respectively (Eq. (11.1)) [51]. Denmark found that the major product of the BF3 OEt2-promoted reaction of 15 was adduct 16, which must arise from the synclinal, anti S e transition state 19. The minor adduct 17 must ari.se through the antiperiplanar transition state 20. 

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