Enolates, tin

Boron and tin enolates give much improved selectivity... 

Tin enolates of ketones can be generated by the reaction of the enol acetate 733 with tributyltin methoxide[60i] and they react with alkenyl halides via transmetallation to give 734. This reaction offers a useful method for the introduction of an aryl or alkenyl group at the o-carbon of ketones[602]. Tin enolates are also generated by the reaction of siiyl enol ethers with tributyltin fluoride and used for coupling with halides[603]. 

TSUJi - TROST Allylatlon Direct C-allyiallon a) ketones or of tin enol ethers with Pd(OJ catalysts. 

In a similar way. ft-keto imide 19 undergoes stereodivergenl aldol reactions. Thus, conversion of 19 into the tin enolate, and subsequent addition of aldehydes, give predominantly the diastereomers 20. On the other hand, hydroxy ketones 21 are the main products when the chlorotitanium enolate of 19 is reacted with aldehydes53. ... 

The related serine derived (4S)-4-methoxycarbonyl-3-(l-oxopropyl)-2-thiono-l,3-oxazolidine 11, and the cysteine derived (4A)-4-methoxycarbonyl-3-(l-oxobntyl)-2-thiono-1,3-thiazolidine 13, also serve as efficient chiral auxiliaries in boron- and tin(II)-mediated aldol condensations98. Thus, conversion of 11 into the boron or tin enolate, followed by reaction with 2-methylpropanal affords predominantly one adduct. Subsequent methanolysis and chromatographic purification delivers the syu-methyl ester in 98% ee. 

A high preference for the formation of. syw-adducts combined with remarkable induced diastereoselcctivity is also obtained with the boron enolate of 1598a and the tin enolate of 1698b. 

The second approach for the synthesis of 2-amino-3-hydroxycarboxylic acids starts with a chiral isothiocyanate which is added, via the tin enolate, to aldehydes. The initially formed adducts are immediately derivatized to the heterocycles, from which. yj 7-2-amino-3-hy-droxycarboxylic acids result after a three-step procedure. The diastereomeric ratios of the intermediate bis-heterocyclic products range from 93 7 to 99 1 (desired isomer/sum of all others)104. 

In contrast to the closely related chiral imide (vide supra), the chiral (4S)-3-acetyl-4-ethyl-2-thiono-l,3-thiazolidine reacts, via the tin enolate, with a,/(-unsaturated aldehydes in a fairly stereoselective manner (d.r. 93 7 to 97.3 2.7)11... 

Higher degrees of induced stereoselectivity are obtained using the chiral (4,S )-3-acetyl-4-iso-propyl-l,3-thiazolidin-2-one where, once again, the tin enolate is most efficient. 3-Hydroxy ester 12 is accessible in 94% ee by this aldol variation112. 

Transmetalation of lithium enolate 1 a (M = Li ) by treatment with tin(II) chloride at — 42 °C generates the tin enolate that reacts with prostereogenic aldehydes at — 78 °C to preferentially produce the opposite aldol diastereomer 3. Diastereoselectivities of this process may be as high as 97 3. This reaction appears to require less exacting conditions since similar results are obtained if one or two equivalents of tin(ll) chloride arc used. The somewhat less reactive tin enolate requires a temperature of —42 C for the reaction to proceed at an acceptable rate. The steric requirements of the tin chloride counterion are probably less than those of the diethyla-luminum ion (vide supra), which has led to the suggestion26 44 that the chair-like transition state I is preferentially adopted26 44. This is consistent with the observed diastereoselective production of aldol product 3, which is of opposite configuration at the / -carbon to the major product obtained from aluminum enolates. 

Reaction of the lithium enolate 2 with prochiral aldehydes at low temperature proceeds with little selectivity, producing all four possible diastereomers 3, 4, 5, and 6 in similar amounts50. Transmetalation of the lithium enolate by treatment with three equivalents of diethylaluminum chloride or with one equivalent of copper cyanide generates the corresponding cthylaluminum and copper enolates which react at — 100°C with prochiral aldehydes to produce selectively diastereomers 1 and 2, respectively50. The reactivity of tin enolates of iron- propanoyl complexes has not been described. 

Similar high /(-methyl selectivities are reported for divalent tin enolates of oxazolidine and thiazolidine derivatives1093. 

As an alternative, tin enolates are very useful in these additions. Usually they are prepared in situ from the amide using tin(II) trifluoromethanesulfonate and a base. They are subsequently reacted with an enone, catalyzed by a Lewis acid47-48 (see Table 3). With triinethylsilyl trifluoromethanesulfonate as a catalyst, in the presence of proline derived diamines anti-adducts are formed exclusively49 (see Section 1.5.2.4.3.1.). 

Table 3. 3-(l,5-Dioxoalkyl)-2-oxazolidinones from Addition of Tin Enolates to Enones47... 

High enantioselectivities may be reached using the kinetic controlled Michael addition of achiral tin enolates, prepared in situ, to a,/i-unsaturated carbonyl compounds catalyzed by a chiral amine. The presence of trimethylsilyl trifluoromethanesulfonate as an activator is required in these reactions236. Some typical results, using stoichiometric amounts of chiral amine and various enolates are given below. In the case of the l-(melhylthio)-l-[(trimethylsilyl)thio]ethene it is proposed that metal exchange between the tin(II) trifluoromethanesulfonate and the ketene acetal occurs prior to the 1,4-addition237,395. 

There is a growing interest in the tin enolates that can be prepared by treating enol acetates with trialkyltin methoxides, e.g. (193),... 

The aminotin compounds react with aldehydes by addition and elimination, to give enamines (219), but some ketones, by acidolysis, give tin enolates, e.g. (220),... 

Organotin enamines can be prepared by treating organotin halides with the lithium or magnesium derivatives of enamines, and also by treating distannazanes with tin enolates (222,223). 

Tin enolates are also used in aldol reactions.27 Both the Sn(II) and Sn(IV) oxidation states are reactive. Tin(II) enolates can be generated from ketones and Sn(II)(03SCF3)2 in the presence of tertiary amines.28 The subsequent aldol addition is syn selective and independent of enolate configuration.29 This preference arises from avoidance of gauche interaction of the aldehyde group and the enolate P-substituent. The syn stereoselectivity indicates that reaction occurs through an open TS. 

In Step D another thiazoline chiral auxiliary, also derived from cysteine, was used to achieve double stereodifferentiation in an aldol addition. A tin enolate was used. The stereoselectivity of this reaction parallels that of aldol reactions carried out with lithium or boron enolates. After the configuration of all the centers was established, the synthesis proceeded to P-D lactone by functional group modifications. 

Bicyclic alkaloids. Nagao et al. have developed a general synthesis of chiral bicyclic alkaloids with a nitrogen atom at the ring juncture, such as pyrrolizidines [5.5], quinolizidines [6.6], and indolizidines [6.5], based on a highly diastereose-lective alkylation of 3-a>-chloroacyl-(4S)-isopropyl-l,3-thiazolidine-2-thiones (1, m = 1,2) with 5-acetoxy-2-pyrrolidinone (2, n = 1) or 6-acetoxy-2-piperidinone (2, n = 2). Thus the tin enolate of 1 (m = 1), prepared with Sn(OTf) and N-... 

Tin enolates can be generated from ketones and Sn(03SCF3)2 in the presence of... 

Iwasawa and Mukaiyama have previously reported the first example of forming highly optically active aldols from aromatic ketones and various aldehydes, again via divalent tin enolates employing chiral diamines derived from (S)-proline as ligands 172>. 

N. Jacobsen of Harvard University has found (J. Am. Chem. Soc. 2005,127, 62) that tin enolates work particularly well with his Cr salen catalyst. A variety of activated alkylation agents give high from the alkylation. It works well for 5-, 6- and 7-membered rings. 

Tin(II) chloride, 298 Titanium(IV) chloride, 304 Trityl perchlorate, 339 With tin enolates Bis(2-pyridinethiolato)tin(II), 40 Norephedrine, 200 With titanium enolates Organotitanium reagents, 213... 

Tetra-substituted tin enolates of ketones, which are otherwise difficult to prepare, can be formed via Fd-catalyzed tin hydride reduction of allyl p-ketocarboxylates (equation 102).294 Allyl (3-ketocarboxy-lates can also be transformed into a-bromo ketones using this method (equation 103).296... 

Tin enolates add to rr-allylpalladium complexes directly on the allyl ligand (inversion).106 383 Therefore, in tandem with the inversion of configuration incurred in the oxidative addition of a Pd° catalyst into an allyl acetate, a net overall retention is observed (equation 155). 

The direct coupling of the tin enolate (175 Scheme 25) with (30) gives complex (176) in good yield (87%). Fortuitously, the bond formation gives approximately a 5 1 mixture in favor of the diastereomer required for trichothecene synthesis. Further elaboration of the major isomer leads to (i)-trichodiene (167), representing an eight step diastereoselective total synthesis of the natural product from p-methyl-anisole, which compares very favorably with previous methods.32-36... 

Enholm has reported tandem cyclizations induced by RsSnH (Scheme 38)101. The initial cyclization is a A5-hexeny 1-type cyclization of the initially formed radical anion (61 — 62). After hydrogen transfer from R3SnH, the resulting tin enolate 63 undergoes nucleophilic addition to the nitrile. 

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