Enol Ethers Synthesis from enols

P 55] Before synthesis, a micro-mixing tee chip micro reactor (Figure 4.85) (with two mixing tees and four reservoirs) was primed with anhydrous tetrahydrofuran (THF). A 40 gl volume of a 0.1 M solution of tetrabutylammonium fluoride trihydrate in anhydrous THF is filled into one reservoir of a micro-mixing tee chip reactor [15], 40 gl of a 0.1 M solution of 4-bromobenzaldehyde in anhydrous THF is added to a second reservoir, 40 gl of a 0.1 M solution of the silyl enol ether (masking the enolate of a carbonyl compound such as cyclohexanone) in anhydrous THF is added to a third reservoir and anhydrous TH F is filled into the fourth collection reservoir. Electrical fields of417,455,476 and 0 V cm are applied to transport the reaction species from the respective reservoirs. The reaction is carried out at room temperature. 

The illustrative example is the synthesis of heptane-2,5-dione (Expt 5.105). A related reaction is the interaction of a silyl enol ether, derived from a ketone, with a nitro olefin in the presence of either titanium(iv) chloride or... 

Nevertheless, the use of chirally modified Lewis acids as catalysts for enantioselective aminoalkylation reactions proved to be an extraordinary fertile research area [3b-d, 16]. Meanwhile, numerous publications demonstrate their exceptional potential for the activation and chiral modification of Mannich reagents (generally imino compounds). In this way, not only HCN or its synthetic equivalents but also various other nucleophiles could be ami-noalkylated asymmetrically (e.g., trimethylsilyl enol ethers derived from esters or ketones, alkenes, allyltributylstannane, allyltrimethylsilanes, and ketones). This way efficient routes for the enantioselective synthesis of a variety of valuable synthetic building blocks were created (e.g., a-amino nitriles, a- or //-amino acid derivatives, homoallylic amines or //-amino ketones) [3b-d]. 

The silatropic ene pathway, i.e. direct silyl transfer from an enol silyl ether to an aldehyde, might be a possible mechanism in the Mukaiyama aldol-type reaction. Indeed, ab initio calculations show the silatropic ene pathway, involving the cyclic (boat and chair) transition states for the BHs-promoted aldol reaction of the trihydro-silyl enol ether derived from acetaldehyde with formaldehyde, to be favored [94], We recently reported the possible intervention of a silatropic ene pathway in the asymmetric catalytic aldol-type reaction of silyl enol ethers of thioesters [95]. The chloro and amino compounds thus obtained are useful intermediates in the synthesis of carnitine and GABOB (Sch. 34) [96]. 

For the synthesis of (69), the enol ether (71) from the indanone (70) was carboxylated with COa-n-butyl-Iithium in THF at —70 C to yield (72). The methyl ester (73) was converted into (75) via the maleic anhydride adduct (74), essentially as described in earlier work. Lithium aluminium hydride reduction followed by oxidation with dicyclohexylcarbodi-imide afforded the aldehyde (76). This was condensed with excess (77) to yield a mixture of the diastereomers (78). Oxidation with chromium trioxide-pyridine in methylene dichloride gave (79), which could be converted into the diketone (80) by treatment with excess benzenesulphonylazide. The diketo-lactam (81) was prepared from (80) as described for the synthesis of the analogous intermediate used in the synthesis of napelline. Reduction of (81) with lithium tri-t butoxyaluminohydride gave the desired dihydroxy-lactam (82). Methylation of (82) with methyl iodide-sodium hydride gave (83). Reduction of this lactam to the amine (84) with lithium aluminium hydride, followed by oxidation with potassium permanganate in acetic acid, gave (69). 

The use of these auxiliaries in anti aldol reactions has been described, though not by generation of the anticipated ( )-enolate. Instead, the typical (Z)-enolate is formed, and then precomplexation of a Lewis acid with the reacting aldehyde diverts the reaction away from a cyclic transition state [23]. The contrasting stereochemical trends of the catalyzed and non-catalyzed reactions are evident in an early approach to muamvatin (Scheme 9-13) [24]. Alternatively, Oppolzer has reported the Lewis acid catalyzed anti aldol reaction of a silyl enol ether derived from sultam 38 [25]. In general, however, this methodology has seen limited use in the synthesis of complex natural products. 

Given this problem, the attachment of the butanone synthon to aldehyde 74 prior to the methyl ketone aldol reaction was then addressed. To ovenide the unexpected. vTface preference of aldehyde 74, a chiral reagent was required and an asymmetric. syn crotylboration followed by Wacker oxidation proved effective for generating methyl ketone 87. Based on the previous results, it was considered unlikely that a boron enolate would now add selectively to aldehyde 73. However, a Mukaiyama aldol reaction should favour the desired isomer based on induction from the aldehyde partner. In practice, reaction of the silyl enol ether derived from 87 with aldehyde 73, in the presence of BF3-OEt2, afforded the required Felkin adduct 88 with >97%ds (Scheme 9-29). This provides an excellent example of a stereoselective Mukaiyama aldol reaction uniting a complex ketone and aldehyde, and this key step then enabled the successful first synthesis of swinholide A. 

The carbonyl group of an ester function can be converted to the corresponding methylene compound using Tebbe s reagent. The reaction can thus be considered as a general method of enol ether synthesis. An example of this reaction is given in Scheme 5. The same conversion can be achieved by reagents prepared from the reduction of 1,1-dibromoalkanes with zinc and TiCU in the presence of TMEDA. °... 

BOORD Enol ether synthesis Synthesis ol chloroethers and enoi ethers from aliphatic aldehydes. 

The 2-oxyallyl cation has found a number of applications in organic synthesis. These species can be produced from a,a -dibromoketones, from a-halo-trialkylsilyl enol ethers or from allyl sulfones and a Lewis acid. For example, the 2-oxyallyl cation 192 can be prepared from the dibromide 191 and its cycloaddition with furan gave the adduct 193, used in a synthesis of nonactic acid (3.127). These reactions may take a concerted or a stepwise course, depending on the nature of the diene and the allyl cation and the reaction conditions. 

The DMP oxidation of 1,2-diols generally cleaves the glycol C—C bond, as illustrated by the synthesis of tricyclic enol ether 883 from diol 882 via tandem 1,2-diol cleavage-intramolecular cycloaddition (Scheme 3.355) [1220]. 

The structure (83) of toxin I from the fungus Altemaria citri (7) has been verified by synthesis of its 3-methyl enol ether (84) from glucose (95). 

The mechanistic rationale for the dramatic Lewis acid effect on the course of the Engler indole/benzofuran synthesis involving styrenes is illustrated in Scheme 3. Whereas titanium forms a bidentate complex 11 with the C-1 carbonyl and C-alkoxy oxygens, which leads to the dihydroindole (equation 1), boron trifluoride engages in monodentate complexation 12 with the sulfonyl nitrogen, leading to dihydrobenzofuran formation (equation 2) [3, 4]. Likewise, the reaction between 11 and an enol ether derived from 4-piperidone is depicted in equation 3 [5]. 

Another silyl enol ether synthesis developed by Reich utilized systems where the Brook rearrangement led to y elimination from the... 

The concept of silyl enol ether synthesis via / -elimination from a Brook rearrangement-derived carbanion also appeared in Wicha s studies on additions of 1-phenyl-l//-tetrazol-5-yl (PT) sulfonyl anions to acyl silanes. When PT sulfone 34 was deprotonated in the presence of acyl(triphenyl)silane, ketone 36 was isolated in good yield after hydrolysis of the silyl enol ether intermediate 35. The mechanism involved addition of the... 

Wang W Li YL, Wang XS (2012) Highly efficient synthesis of 7-aryl-pyrano[3,4-c] pyrazolo[4,3-f]quinoline derivatives catalyzed by iodine. ARKIVOC vi 214-221 Lin XF, Cui SL, Wang YG (2006) Molecular iodine catalyzed one-pot synthesis of substituted quinolines from imines and aldehydes. Tetrahedron Lett 47 3127-3130 Jin G, Zhao J, Han J, Zhu S, Zhang J (2010) Iodine-promoted imino-Diels-Alder reaction of fluorinated imine with enol ether synthesis of 2-perfluorophenyl tetrahydroquinoline derivatives. Tetrahedron 66 913-917... 

Since our group (22) and Hehnchen s (23) independently announced a new class of chiral acyloxyboranes derive from iV-sulfonylamino acids and borane THF, chiral 1,3 -oxazaborolidines, their utility as chiral Lewis acid catalysts in enantioselective synthesis has been convincingly demonstrated (2(5). In particular, Corey s tryptophan-derived chiral oxazaborolidines 10a and 10b are highly effective for not only Mukaiyama aldol reactions (24) but also Diels-Alder reactions (25). More than 20 mol% of 10b is required for the former reaction, however. Actually, the reaction of the trimethylsilyl enol ether derived from cyclopentanone with benzaldehyde afforded the aldoI products in only 71% yield even in the presence of 40 mol%of 10b (24). We recently succeed in renewing 10b as a new and extremely active catalyst lOd using arylboron dichlorides as Lewis acid components (2(5). 

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