Enolates aldol reaction with

A powerful variation of the iron acetyl enolate aldol reaction utilizes the cnolate of complex 8 which bears a (pentafluorophenyl)diphenylphosphane ligand in place of the more usual triphenylphosphane47. The enolate species 9. prepared by treatment of 8 with lithium diiso-propylamide, reacts at — 78 °C with benzaldehyde to produce the aldol adduct 10 with a d.r. of 98.5 1.5. 

The a-alkoxy iron-acyl complex 5 may be deprotonated to generate the lithium enolate 6, which undergoes a highly diastereoselective aldol reaction with acetone to generate the adduct 7 as the major product. Deprotonation of acetone by 6 is believed to be a competing reaction 30% of the starting complex 5 is found in the product mixture48 40. 

The achiral molybdenum enolate 2 reacts with benzophenone and benzaldehyde at —78 °C to yield the x,/i-unsaturated molybdenum-acyl complexes34, which presumably arise via elimination of hydroxide from unobserved aldolate intermediates such as 3. No examples of such aldol reactions with complexes that are chiral at molybdenum have been reported. 

For some other aldol reactions with preformed enol derivatives, see Mukaiyama, T. Isr. J. Chem., 1984, 24, 162 Caine, D. in Augustine, Ref 564, p. 264. 

In Section 3.5 on alkene isomerization, it was mentioned that Li and co-workers reported a RuCl2(PPh3)3-catalyzed shuffling of functional groups of allylic alcohols in water (Eq. 3.35).140 Since the reaction proceeds through an enol intermediate, allyl alcohols can thus be considered as enol equivalents.203 This has been developed into an aldol-type reaction by reacting allyl alcohols with aldehyde (Scheme 3.11).204 The presence of In(OAc)3 promoted the aldol reaction with a-vinylbenzyl alcohol and aldehyde.205... 

In the presence of zinc chloride, stereoselective aldol reactions can be carried out. The aldol reaction with the lithium enolate of /-butyl malonate and various a-alkoxy aldehydes gave anti-l,2-diols in high yields, and 2-trityloxypropanal yielded the syn-l,2-diol under the same conditions.633 Stoichiometric amounts of zinc chloride contribute to the formation of aminoni-tropyridines by direct amination of nitropyridines with methoxyamine under basic conditions.634 Zinc chloride can also be used as a radical initiator.635... 

Using a cyclic enone 2-29b and an ester-TMS enolate 2-30 in the presence of catalytic amounts of SmI2(THF)2, the Michael addition and the Mukaiyama/aldol reaction with the added aldehyde 2-32 led to the diastereomeric adducts 2-33 and 2-34 via 2-31 with a dr =80 20 to 98 2 and 70-77% yield (Scheme 2.7) [13]. The major product is the trans-l,2-disubstituted cycloalkanone. 

The stereoselective addition of the titanium enolate of A-acetyl-4-phenyl-l,3-thiazolidine-2-thione 153 to the cyclic A-acyl iminium ion 154 is utilized in the synthesis of (-)-stemoamide, a tricyclic alkaloid <06JOC3287>. The iminium ion addition product 155 undergoes magnesium bromide-catalyzed awtz-aldol reaction with cinnamaldehyde 156 to give adduct 157, which possesses the required stereochemistry of all chiral centers for the synthesis of (-)-stemoamide. 

Several other examples of zz/z/z -diastereoselectivc aldol reactions with titanium enolates and carbonyl electrophiles have been reported in the literature.58-65... 

Compound 17 is the so-called (+)-Prelog-Djerassi lactonic acid derived via the degradation of either methymycin or narbomycin. This compound embodies important architectural features common to a series of macrolide antibiotics and has served as a focal point for the development of a variety of new stereoselective syntheses. Another preparation of compound 17 is shown in Scheme 3-7.11 Starting from 8, by treating the boron enolate with an aldehyde, 20 can be synthesized via an asymmetric aldol reaction with the expected stereochemistry at C-2 and C-2. Treating the lithium enolate of 8 with an electrophile affords 19 with the expected stereochemistry at C-5. Note that the stereochemistries in the aldol reaction and in a-alkylation are opposite each other. The combination of 19 and 20 gives the final product 17. 

Besides their application in asymmetric alkylation, sultams can also be used as good chiral auxiliaries for asymmetric aldol reactions, and a / -product can be obtained with good selectivity. As can be seen in Scheme 3-14, reaction of the propionates derived from chiral auxiliary R -OH with LICA in THF affords the lithium enolates. Subsequent reaction with TBSC1 furnishes the 0-silyl ketene acetals 31, 33, and 35 with good yields.31 Upon reaction with TiCU complexes of an aldehyde, product /i-hydroxy carboxylates 32, 34, and 36 are obtained with high diastereoselectivity and good yield. Products from direct aldol reaction of the lithium enolate without conversion to the corresponding silyl ethers show no stereoselectivity.32... 

On the other hand, Ln(OTf)3 compounds, which were found to be effective catalysts for the hydroxy-methylation in aqueous media, also activate aldehydes other than formaldehyde in aldol reactions with silyl enol ethers in aqueous solvents.1121 One feature of the present reactions is that water-soluble... 

Very recently, a tandem sequence consisting of enolboration/hydroform-ylation/aldol reaction has been described [88]. Here configuration of the enol boronate is transferred to the aldol product, allowing good to excellent di-astereoselectivities in the hydroformylation/aldol reaction. With this method, 5-7-membered rings are obtained in excellent yields (Scheme 35). 

Murai and coworkers reported on operationally simple aldol reactions with lithium enolates generated from carbonylation of silylmethyl lithium species [57]. Upon 1,2-silicon shift, a-silyl acyllithium species can be stereo-selectively converted to (E) lithium enolates that undergo addition to aldehydes to give /3-hydroxy acylsilanes (Scheme 14). 

Perlmutter used an oxymercuration/demercuration of a y-hydroxy alkene as the key transformation in an enantioselective synthesis of the C(8 ) epimeric smaller fragment of lb (and many more pamamycin homologs cf. Fig. 1) [36]. Preparation of substrate 164 for the crucial cyclization event commenced with silylation and reduction of hydroxy ester 158 (85-89% ee) [37] to give aldehyde 159, which was converted to alkenal 162 by (Z)-selective olefination with ylide 160 (dr=89 l 1) and another diisobutylaluminum hydride reduction (Scheme 22). An Oppolzer aldol reaction with boron enolate 163 then provided 164 as the major product. Upon successive treatment of 164 with mercury(II) acetate and sodium chloride, organomercurial compound 165 and a second minor diastereomer (dr=6 l) were formed, which could be easily separated. Reductive demercuration, hydrolytic cleavage of the chiral auxiliary, methyl ester formation, and desilylation eventually led to 166, the C(8 ) epimer of the... 

The lithium enolate of di-i-butyl malonate undergoes a stereoselective aldol reaction with Qf-alkoxyaldehydes to give anft-l,2-diol derivatives in the case of the highly hindered 2-trityloxypropanal, the stereochemistry is reversed. 

Diisobutylaluminium phenyl tellurolate, a highly air- and moisture-sensitive reagent, prepared by reaction of diisobutylaluminium hydride with diphenyl ditelluride, undergoes an in situ addition to a,jS-unsaturated carbonyl compounds, leading to the corresponding jS-phenyltelluroaluminium enolate. This intermediate is hydrolysed by aqueous HCl into jS-phenyltelluro compounds or smoothly affords an aldol reaction with aldehydes to give a-hydroxyalkyl-jS-phenyltellurocarbonyl compounds. 

Hydroxycoumarin can be considered as an enol tautomer of a 1,3-dicarbonyl compound conjugation with the aromatic ring favours the enol tautomer. This now exposes its potential as a nucleophile. Whilst we may begin to consider enolate anion chemistry, no strong base is required and we may formulate a mechanism in which the enol acts as the nucleophile, in a simple aldol reaction with formaldehyde. Dehydration follows and produces an unsaturated ketone, which then becomes the electrophile in a Michael reaction (see Section 10.10). The nucleophile is a second molecule of 4-hydroxycoumarin. 

Next to phosphoramides, Denmark reported an axially chiral A -oxide to catalyze the asymmetric aldol reaction of trichlorosilyl enol ethers with ketones [99]. Hashimoto reported an aldol reaction with 3 mol% of another axially chiral A -oxide [100] which gave good yields and enantioselectivities. 

Huang, X.-T. Chen, Q.-Y. Ethyl a-Fluoro Silyl Enol Ether Stereoselective Synthesis and Its Aldol Reaction with Aldehydes and Ketones. J. Org. Chem. 2002, 67, 3231-3234. 

The general trend then is that boron enolates parallel lithium enolates in their stereoselectivity but show enhanced stereoselectivity. They also have the advantage of providing access to both stereoisomeric enol derivatives. Table 2.3 gives a compilation of some of the data on stereoselectivity of aldol reactions with boron enolates. 

Bismuth triflate has been reported by Dubac as an efficient catalyst for the Mukaiyama aldol reaction with silyl enol ethers [27] and was recently used with a chiral ligand, as reported by Kobayashi in an elegant hydroxymethylation reaction... 

The present procedure is a modification of that originally reported by the submitter and co-workers. This procedure is applicable to a large scale preparation of the title compound in high overall yield (-80%) without purification of the intermediates by chromatography. The title compound is reported to be a useful reagent for anf/-selective aldol reactions with dicyclohexylboron triflate and triethylamine as enolization reagents. ... 

The oxazolidinones have been used as chiral auxiharies for enolate alkylation and aldol reactions in enantioselective and total syntheses The interest in these substrates is largely known for iyw-diastereoselective aldol reactions with chlorotitanium or diaUcylboron oxazilidinone enolates (equation 114). 

A. Dondoni and P. Merino, Chemistry of the enolates of 2-acetylthiazole Aldol reactions with chiral aldehydes to give 3-deoxy aldos-2-uloses and 3-deoxy-2-ulosonic acids. A short total synthesis of 3-deoxy-D-manno-2-octulosonic acid (KDO), J. Org. Chem. 56 5294 (1991). 

---