Aldehydes dienol ethers

Having used their catalytic systems with dienolates derived from unsaturated esters, Denmark performed aldol reactions with the dioxanone-derived dienol ether described above in the context of Carreira s and Campagne s vinylogous aldol reactions (Scheme 21). Here, exclusively, the y product was formed with the nucleophile attacking from the Re face. For all three aldehydes, very good yields (83-92%) and selectivities (74-89% ee) were observed with only 0.01-0.05 mol% of the catalyst. 

Regio-, enantio-, and diastereo-selective vinylogous aldol additions of silyl dienol ethers to aldehydes use a Lewis base (a chiral bis-BINAP-phosphoramide) to activate a Lewis acid (silicon tetrachloride).139... 

Catalytic, enantioselective addition of silyl ketene acetals to aldehydes has been carried out using a variant of bifunctional catalysis Lewis base activation of Lewis acids.145 The weakly acidic SiCU has been activated with a strongly basic phor-phoramide (the latter chiral), to form a chiral Lewis acid in situ. It has also been extended to vinylogous aldol reactions of silyl dienol ethers derived from esters. 

According to Section 12.3 enamines are just one synthetic equivalent for enols that are not sufficiently represented in equilibrium with a carhonyl compound to allow for a-functional-izations. Enol ethers and silyl enol ethers, which are addressed in this section, are other synthetic equivalents for such enols. An enol ether, for example, is used as an enol equivalent for aldehyde enols, since several aldehydes do not form stable enamines. In addition, enol ethers or silyl enol ethers are usually employed as synthetic equivalents for the enols of ,/i-unsatu-rated carbonyl compounds. The attempt to react ce,/ -unsaturated carhonyl compounds with secondary amines to give a dienamine is often frustrated by a competing 1,4-addition of the amine. The combination of these factors turns the dienol ether B of Figure 12.23 into a species for which there is no analog in enamine chemistry. 

Denmark reported a protocol for the formation of 3-substituted azepines 4 from nitro acylsilanes 3, which were formed by the conjugate addition of an acylsilane-derived dienol-ether 2 to nitroalkenes 1 <07JOC7050>. The reaction of the nitro acylsilane with aluminium-amalgam gave a mixture of azepines and lactams, however, this was overcome by conversion of the acylsilane to an aldehyde prior to the reductive cyclisation. 

Regioselective Peterson reaction. Aldehydes react with the anion of an (a-al-koxy)allyltrimethylsilane (1) at both a- and y-positions. Addition of HMPT favors reaction at the y-position, whereas addition of Ti(0-/-Pr)4 (1 equiv.) results in exclusive reaction at the a-position to give an (E)-l, 3-dienol ether (2). These products are readily hydrolyzed to vinyl ketones (3).4... 

Dienolic ethers (379), in contrast with the acetates, are cleaved by peroxy-acid at the 3,4-unsaturated link under anhydrous conditions, giving carbo-methoxy-aldehydes (380). The reaction is probably mechanistically similar to the oxidative cleavage of dihydropyrans e.g. 381 — 382), although the... 

Seebach and co-workers have explored the uses of enantiomerically pure dienolates (18) and silyl dienol ethers derived from dioxinones as chiral synthetic equivalents of the acetoacetic ester dianion. Reactions were carried out principally with aldehydes, and are regio- and diastereoselective (Scheme 7) <89AG(E)472,91CB1845>. 

A new approach to the 0-functionalisation of enones involves treating the substrate with t-butyldimethylsilyl triflate (TBDMSOTf) in the presence of triphenylphosphine. This phosphoniosilylation reaction gives a silylenol ether-wittig salt which, after lid formation, may be condensed with an aldehyde to give a silyl dienol ether. These may either be protiodesilylated to give the 0-functionalised enone or alternatively used in aldol... 

Mono-enolisation of a 1,5-diketone, then the formation of a cyclic hemiacetal, and its dehydration, produces dienol ethers (4//-4-pyrans) which require only hydride abstraction to arrive at the pyrylium oxidation level. The diketones are often prepared in situ by the reaction of an aldehyde with two mols of a ketone (compare Hantzsch synthesis, section 5.15.1.2) or of a ketone with a previously prepared conjugated ketone - a chalcone in the case of aromatic ketones/aldehydes. It is the excess chalcone which serves as the hydride acceptor in this approach. 

Three-carbon homologation of aldehydes, and also of cyclic and acyclic ketones to form a/8-unsaturated aldehydes, can be performed by treating the carbonyl compounds with 3-methoxyallylidenetriphenylphosphorane (23) followed by in situ hydrolysis of the dienol ether (Scheme 53). ... 

Vinylogous aldol-type reaction of aromatic and heteroaromatic aldehydes with silyl dienol ethers 21.115, derived from a,p-unsaturated esters, also proceeded smoothly, furnishing exclusively the y-addition products 21.116 (>99 1) with high enantioselectivity in the range of 82-98%... 

The reaction of trimethylsilyl dienol ethers with PdCl2(NCMe)2 affords palladium 7 -allyls with an aldehyde functionality (Equation (38)). The actual mechanism of the reaction was not discussed but the rearrangement of a palladium enolate transferred from the siloxane moiety seems plausible. A related rearrangement has been observed in a Pd aryloxide that leads to a bis 77 -allylic Pd complex, as was discussed in Section 8.06.3. - ... 

Denmark SE, Heemstra JR Jr (2004) Lewis base activation of lewis acids vinylogous aldol additions of dienol ethers to aldehydes. Synlett 2411-2416... 

In the presence of titanium(IV) chloride, silyl dienol ether 55 derived from an a,/i-unsaturated aldehyde reacts tvith acetal 54 selectively at the y-position to give d-alkoxy-a,j5-unsaturated aldehydes 56, albeit in lotv yields. Because titanium(IV) chloride is strongly acidic, polymerization of silyl dienol ether 55 proceeds. In these reactions addition of tetraisopropoxyti-tanium(IV) to titanium(IV) chloride increases the yield dramatically [28a] -vitamin A is successfully synthesized by utilizing this aldol reaction of silyl dienol ether 55 (Scheme 3.2) [28b]. 

Moving forward from 59, six steps were required to convert this compound to 60. Vicinal dihydroxylation of the olefin was followed by oxidative cleavage of the intermediate diol using lead tetraacetate. Reductive amina-tion of the resulting aldehyde with methylamine, followed by acylation of the intermediate secondary amine gave the desired carbamate. Swern oxidation of the secondary alcohol, followed by enol ether formation gave 60. Elimination of -toluenesulfinic acid from 60 provided 61. Oxidation of this dienol ether to dienone 62 was followed by release of the secondary amine, followed by a conjugate addition reaction to establish the critical C-N bond. The remainder of the synthesis followed known chemistry. The mixture of enones 63 was converted to codeinone (35), codeine (3) and then morphine (1). 

The authors assumed that the catalytically active species might be a copper(I) complex originating from reduction by the silyl dienolate 214. As a consequence, the aldol reaction was performed with the chiral copper(I) complex [Cu(OfBu)-(S)-270], and identical results in terms of the stereochemical outcome were obtained. In addition, the reaction was followed by react IR. The study led to evidence of a copper(I) enolate as the active nucleophile, and the catalytic cycle also shown in Scheme 5.77 was proposed. The reaction of the copper(I) complex Cu(OiBu)-(S)-270 with silyl dienolate 214 represents the entry into the catalytic cycle. Under release of trimethylsilyl triflate, the copper enolate 272 forms, whose existence is indicated by in situ IR spectroscopy. Its exact structure remains unclear, but the description as O-bound tautomer is plausible. Upon reaction with the aldehyde, the copper aldolate 273 is generated, which is then silylated by means of the silyl dienol ether 214 to give the (isolable) silylated alcohol 274 from which the aldol product 271 is liberated during the acidic workup [132b]. 

This system could be evolved into the catalytic enantioselective vinylogous aldol reactions [10, 11]. For example, the reaction of crotonate-derived dienol ether with benzaldehyde proceeded smoothly in the presence of 2 to give the y-addition product exclusively with rigorous enantiocontrol (Scheme 7.8). This protocol tolerated the use of aliphatic aldehydes such as 3-phenylpropanal as an electrophile and has found fruitful applications in the total synthesis of natural products [12]. 

Silyl dienol ethers also participate in the asymmetric aldol-type transformation. For example, silyl 1,3-dienol ethers react with aldehydes exclusively at the diene terminus in an enantioselective manner in the presence of a chiral titanium (Scheme 3-81) or copper catalyst, whereas the asymmetric reaction of... 

Hex- and hept-2-en-4-yn-l-ol gave hexa-3,4-dienol and hepta-3,4-dienol, respectively. The absolute configuration of ( + )-hexa-3,4-dienol was determined to be S by thermal conversion of (- )-(S)-a-chloroethyl l-methylprop-2-ynyl ether (18) to an allenic aldehyde 19, which was reduced with LAH to (+ )-hexa-3,4-dienol (17, R = Me). (See Scheme 2.)... 

Campagne and Bluet recently reported the catalytic asymmetric vinylogous Mukaiyama aldol (CAVM) reaction of aldehydes with dienol silyl ether 15 using chiral ammonium fluorides as an activator. For example, the CAVM reaction of isobutyr-aldehyde with 15 in the presence of 10 mol% of 4b in THF at room temperature led to the formation of the vinylogous aldol product 16 in 70% yield with 20% ee. The ee-value was improved to 30% by conducting the reaction at 0 °C (Scheme 9.6) [16]. 

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