Glyoxylates homoallylic

Si. rra(pentafluorophenyl)boron was found to be an efficient, air-stable, and water-tolerant Lewis-acid catalyst for the allylation reaction of allylsilanes with aldehydes.167 Sc(OTf)3-catalyzed allylations of hydrates of a-keto aldehydes, glyoxylates and activated aromatic aldehydes with allyltrimethylsilane in H2O-CH3CN were examined. a-Keto and a-ester homoallylic alcohols and aromatic homoallylic alcohols were obtained in good to excellent yields.168 Allylation reactions of carbonyl compounds such as aldehydes and reactive ketones using allyltrimethoxysilane in aqueous media proceeded smoothly in the presence of 5 mol% of a CdF2-terpyridine complex (Eq. 8.71).169... 

Mikami reported a highly enantioselective carbonyl-ene reaction where a chiral titanium complex 11 prepared from enantiomerically pure binaphthol (BINOL) and Ti(0-i-Pr)2Br2 catalyzed a glyoxylate-ene reaction with a-methylstyrene to give chiral homoallyl alcohol 12 with 94.6% ee [22]. In this reaction, a remarkable asymmetric amplification was observed and almost the same enantioselectivity (94.4% ee) was achieved by using chiral catalyst prepared... 

Indium-mediated reaction of 4-bromo-l,l,l-trifluoro-2-butene with aldehydes in water proceeds stereoselectively to afford the /Ttrifluoromethylated homoallylic alcohols. Aldehydes with no chelation ability shows //////-selectivity, whereas high. //-selectivity has been attained with 2-pyridinecarboxaldehyde and glyoxylic acid (Scheme 23).134-136... 

The esters are prepared by reaction of the allylic or homoallylic alcohol with the tosylhydrazone of glyoxylic acid chloride- and N,N-dimethylaniline as a base, followed by elimination of /j-toluenesulfinic acid (triethylamine). Yields of —75% can be obtained. 

Reaction of alkenes with carbonyl compounds or carbonyl derivatives in the presence of Lewis acids, the ene reaction, enables the stereoselective preparation of highly functionalized compounds. Copper Lewis acids activate both aldehydes and imines in ene reactions. Evans has reported that Cu(II) Lewis acids catalyze glyoxylates in reactions with alkenes (Sch. 56) [103]. The homoallylic alcohols 257 and 259 are produced in high yield and enantioselectivity. The bis aquo complex 260 is a readily prepared and air-stable catalyst and gave high chemical yield and excellent selectivity in the ene reactions. Another point of note is that catalysts 260 and 261 furnish enantiomeric products even though they differ from each other only by the substituent at the 4-posi-tion of the oxazoline. 

Addition to C=0. Hydrates of a-ketoaldehydes react selectively at the aldehyde group with allylsilanes under the influence of YbfOTfjj at room temperature. The allylation of aldehydes with allylstannanes is accelerated by benzoic acid." Another method for the synthesis of homoallylic alcohols is by the ene reaction, thus y,6-unsaturated a-hydroxy esters are obtained from glyoxylic esters at room temperature in a catalyzed process. ... 

Another enantiosdective variant of this reaction has been developed with a bi-nol-titanium complex 66 [46]. This catalyst affords homoallylic alcohols in moderate diastereo- and enantioselectivity with 2-butenylsilane ( )-16 and methyl glyoxylate (Scheme 10-25). Reaction of (Z)-16 was much less selective, providing homoallylic alcohols with low enantioselectivity. An antiperiplanar transition structure accounts for the formation of the syn homoallylic alcohol 67. A more reactive complex formed from BINOL and TiF4 has also found utility [46cj. 

A highly stereoselective synthesis of trifluoromethylated homoallylic alcohols is possible using the transmetallation [Sn(II) to In(IIl)] pathway [205], The indium trichloride/tin-promoted reaction of trifluorobromobutene with various aldehydes afforded the homoallylic alcohols in extremely high yield and diastereos-electivity (Scheme 10-105). The strong preference for the anti products with the simple aldehydes is expected on the basis of previous observations with 2-buteny-lindium reagents explained by the cyclic transition structure xxxiv shown. The syn homoallylic alcohol was obtained upon reaction of glyoxylic acid and 2-pyri-dinyl carboxaldehyde. The syn products were proposed to arise by reaction via the 5-membered chelate transition structures xxxv and xxxvi. 

Kresze and coworkers have found about a three order of magnitude rate increase in imino ene reactions when an N-tosyl group is replaced with an N-perfluoroalkanesulfonyl moiety [87]. Thus, with the glyoxylate ester-derived imine and the one from chloral 255 as the enophiles, reactions with acyclic olefins are very rapid and occur at room temperature [Eq. (60)]. In these ene reactions one stereoisomeric homoallylic amine 256 was typically generated, although the stereochemistry was not elucidated. However, in one reported case a 1 1 mixture of diastereomers was obtained. Mechanistic studies based upon kinetic isotope effects seem to indicate that this reaction may in fact be a two-step process rather than a concerted one [87b]. 

Excellent yields of ene adducts have been obtained in Lewis acid catalyzed intramolecular ene reactions of homoallylic glyoxylates. Treatment of (120) with SnCU in nitromethane provides (121) in 85% yield. Similar treatment of (122) gives (123) in 50-60% yield, which was converted to actino-bolin. Allylic glyoxylates decompose in the presence of Lewis acids but give modest yields of ene adducts in thermal reactions (Scheme 19). ... 

The carbonyl-ene reaction is a source of homoallylic alcohols, although the scope is somewhat limited. Synthesis of chiral tertiary a-hydroxycarboxylic esters from glyoxyUc esters has been studied, and many metal catalysts of varying degree of effectiveness have been identified. The Ag-catalyzed reaction between enol silyl ethers and a glyoxylic ester is stericaUy controlled by the Pd-SEGPHOS complex. ... 

Mechanistically related to the Mukaiyama aldol reaction, the carbonyl ene reaction is the reaction between an alkene bearing an allylic hydrogen and a carbonyl compound, to afford homoallylic alcohols. This reaction is potentially 100% atom efficient, and should be a valuable alternative to the addition of organometallic species to carbonyl substrates. However, the carbonyl ene reaction is of limited substrate scope and works generally well in an intermolecular manner only with activated substrates, typically 1,1-disubstituted alkenes and electron-deficient aldehydes (glyoxylate esters, fluoral, a,p-unsaturated aldehydes, etc.), in the presence of Lewis acids. The first use of chiral catalyst for asymmetric carbonyl ene was presented by Mikami et al. in 1989. ° By using a catalytic amount of titanium complexes prepared in situ from a 1 1 ratio of (rPrO)2titaniumX2 (X = Cl or Br) and optically pure BINOL, the homoallylic alcohols 70a,b were obtained in... 

The ene reaction of carbonyl compounds with alkenes is a potentially valuable route to homoallylic alcohols. With reactive, i.e., electron deficient aldehydes such as chloral or methyl glyoxylate, these reactions can be carried out thermally at 100-200 °C or with Lewis acid catalysis at ambient temperature. 1 Formaldehyde undergoes ene reactions with alkenes at 180 C and undergoes Lewis acid catalyzed ene reactions at ambient temperatures with alkenes which can give a tertiary carbocation.3 In the presence of Br0nsted acids, aldehydes and alkenes undergo the Prins... 

Carbonyl-ene reactions of alkenes and glyoxylates were promoted effectively by Yb(OTf)3 [18]. With 20mol% of catalyst loading, desired homoallylic alcohols were obtained in good to high yield (Table 13.7). The reaction with diene gave the mixture of an ene product and a Diels-Alder product. Nakagawa et al reported imino ene reaction between alkenes and imines promoted by Yb(OTf)3-TMSCl (or... 

Me02CCH0/H+ -7.90 eV, vide infra), by the BINOL-Ti catalyst (1) (Table 1). The reaction was carried out by simply adding an olefin and tfien freshly dehydrated and distilled fluoral (2a) at 0 C to the solution of the chiral titanium complex (1) prepared from (/ )- or (5)-BINOL and diisopropoxytitanium dihalide in the presence of molecular sieves MS 4A as described for die glyoxylate-ene reaction (5). The reaction was completed widiin 30 min. The ene-type product, namely homoallylic alcohol (3) was obtained along with the allylic alcohol (4) (entries 1-4). The enantiomeric purities of both products were determined to be more than 95% ee by 1h NMR analysis after transformation to the (5)- and (/ )-MTPA ester derivatives. Thus, the absolute configuration of the products was determined by the Mosher method (8). The sense of asymmetric induction is, therefore, exactly the same as observed for the glyoxylate-ene reaction the (/ )-catalyst provides the (/ )-alcohol products (5). 

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