Lewis base-promoted addition

There are very few examples of Lewis base-promoted allylations of aldehydes with allylstannanes. In 1992 Baba disclosed an intriguing method for allylation of aldehydes with allyl- and 2-butenyltributylstannanes in the presence of catalytic-amounts of dibutyltin dichloride and certain coactivators such as tetrabutylammo-nium iodide, tributylphosphine oxide, HMPA or tetraphenylphosphonium iodide [76]. No definitive mechanistic information is available on the role of the co-activators the authors speculate that the ligands accelerate the metathesis to form allyldibutyltin chloride which is the actual nucleophile. The same group has recently reported the use of a lead(II) iodide/HMPA catalyst for the allylation of a,yff-epoxyketones [76bj. 

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Leighton has combined this concept of strained silacycles [62-66] with the asymmetric allylation chemistry in a series of pubhcations [60, 67-70], Leighton s aUyhc silacyclopentane 29 [67] (Scheme 20) works equally for allylation of aromatic and ahphatic aldehydes in the absence of additional Lewis bases (promoter activator) or Lewis acids with high yield and enantioselectivity. The mechanism of... 

Asymmetric aldol additions of geometrically defined trichlorosilyl enolates of ketones to aliphatic and aromatic aldehydes have been carried out uncatalysed, and with a chiral phosphoramide as Lewis base promoter.54 Significant differences in rates and diastereoselectivities are interpreted in terms of the changeover from a boat-like transition state, with pentacoordinate siliconate, to a chair-like transition state with hexacoordination. 

NHC-catalyzed organocascades allowing the creation of both a C-C and a C-X bonds are rare. The group of Rovis has recently proposed a domino Michael/Stetter reaction for the preparation of optically active benzofuranones from salicylaldehydes and dimethyl acetylenedicarboxylate (DMAD) under dual catalytic conditions (Scheme 16.45) [94]. The reaction sequence involves a Lewis base-promoted oxa-Michael addition to produce a prochiral intermediate that then undergoes an NHC-catalyzed enantiodiscriminative Stetter reaction. Remarkably, the Lewis base not only triggers the initial oxa-Michael addition, but also serves as a Brpnsted base for deprotonation of the NHC precatalyst. The reaction scope could be extended to unsymmetrical alkynes and allenes with moderate to good stereoselectivities. 

Aldol Additions to Ketones. Traditionally, cerium enolates or the Reformatsky-type reaction have been employed to achieve high-yielding aldol additions to enolizable ketones. In this regard, methyl trichlorosilyl ketene acetal provides a reliable alternative for the synthesis of tertiary -hydroxy esters. In the absence of a Lewis base promoter, the aldol additions of 1 to ketones are too slow to be synthetically useful. On the contrary, with pyridine A-oxide as catalyst, methyl trichlorosilyl ketene acetal reacts smoothly with nearly all classes of ketones (7) (Scheme 1). Good yields of the tertiary alcohol products (8) are obtained (eq 4), table 2 from aromatic (entries 1-2 and 4—6), hetereoaromatic (entry 3), olefinic (entries 7-8), acetylenic (entries 9-10), and aliphatic (entries 11-14) ketones. The only poorly performing substrate is 2-tetralone (7o), which affords a 45% yield of the addition product and returns 45% of unreacted starting material, most likely from competitive enolization. 

Denmark SE, Pham SM (2000) Kinetic analysis of the divergence of reaction pathways in the chiral lewis base promoted aldol addition of trichlorosilyl enolates a rapid injection NMR study. Helv Chim Acta 83 1846-1853... 

GopolymeriZation Initiators. The copolymerization of styrene and dienes in hydrocarbon solution with alkyUithium initiators produces a tapered block copolymer stmcture because of the large differences in monomer reactivity ratios for styrene (r < 0.1) and dienes (r > 10) (1,33,34). In order to obtain random copolymers of styrene and dienes, it is necessary to either add small amounts of a Lewis base such as tetrahydrofuran or an alkaU metal alkoxide (MtOR, where Mt = Na, K, Rb, or Cs). In contrast to Lewis bases which promote formation of undesirable vinyl microstmcture in diene polymerizations (57), the addition of small amounts of an alkaU metal alkoxide such as potassium amyloxide ([ROK]/[Li] = 0.08) is sufficient to promote random copolymerization of styrene and diene without producing significant increases in the amount of vinyl microstmcture (58,59). 

Further work by the Ye group has shown that NHCs derived from pre-catalyst 215 can also promote the asymmetric dimerisation of alkylarylketenes 193 to generate alkylidene P-lactones 216 in good diastereo- and enantio-selectivity [83], The asymmetric [4+2] addition of enones and alkylarylketenes to generate 8-lactones 218 in high ee has also been accomplished [84], as has the asymmetric esterification of alkylarylketenes to give esters 217 using benzhydrol, which is assumed to proceed via a Lewis-base mediated mechanism (Scheme 12.46) [85]. 

Summary of the Relationship between Diastereoselectivity and the Transition Structure. In this section we considered simple diastereoselection in aldol reactions of ketone enolates. Numerous observations on the reactions of enolates of ketones and related compounds are consistent with the general concept of a chairlike TS.35 These reactions show a consistent E - anti Z - syn relationship. Noncyclic TSs have more variable diastereoselectivity. The prediction or interpretation of the specific ratio of syn and anti product from any given reaction requires assessment of several variables (1) What is the stereochemical composition of the enolate (2) Does the Lewis acid promote tight coordination with both the carbonyl and enolate oxygen atoms and thereby favor a cyclic TS (3) Does the TS have a chairlike conformation (4) Are there additional Lewis base coordination sites in either reactant that can lead to reaction through a chelated TS Another factor comes into play if either the aldehyde or the enolate, or both, are chiral. In that case, facial selectivity becomes an issue and this is considered in Section 2.1.5. 

However, in the presence of a suitable Lewis base the polymerization becomes living, due to the nucleophihc stabilization of the growing cation generated by the added base. (3) Initiator, strong Lewis acid and onium salt as additive The previous method cannot be easily applied in polar media. In this case the living cationic polymerization is promoted by the addition of salts with nucleophihc anions, such as ammonium and phosphonium derivatives. 

Additions to quinoline derivatives also continued to be reported last year. Chiral dihydroquinoline-2-nitriles 55 were prepared in up to 91% ee via a catalytic, asymmetric Reissert-type reaction promoted by a Lewis acid-Lewis base bifunctional catalyst. The dihydroquinoline-2-nitrile derivatives can be converted to tetrahydroquinoline-2-carboxylates without any loss of enantiomeric purity <00JA6327>. In addition the cyanomethyl group was introduced selectively at the C2-position of quinoline derivatives by reaction of trimethylsilylacetonitrile with quinolinium methiodides in the presence of CsF <00JOC907>. The reaction of quinolylmethyl and l-(quinolyl)ethylacetates with dimethylmalonate anion in the presence of Pd(0) was reported. Products of nucleophilic substitution and elimination and reduction products were obtained . Pyridoquinolines were prepared in one step from quinolines and 6-substituted quinolines under Friedel-Crafts conditions <00JCS(P1)2898>. 

Dialkylzincs are much less reactive than phenyl or alkynylzincs. In 2002, Kozlowski et al. developed a chiral salen-based catalyst 62 that can promote the diethylzinc addition to a-ketoesters in high yield, [Eq. (13.38)]. In their catalysis, titanium acts as a Lewis acid, and amine nitrogen acts as a Lewis base (63). The enantioselectivity was up to 78% ee ... 

Boron enolates bearing menthol-derived chiral ligands have been found to exhibit excellent diastereo- and enantio-control on reaction with aldehydes34 and imines.35 Highly diastereo- and enantio-selective aldol additions of geometrically defined trichlorosilyl ketone enolates (31) and (32) have been achieved by promoting the reactions with chiral Lewis bases, of which (,S., S )-(33) proved to be the most effective.36 Moderate enantiomeric excesses have been achieved by using chiral ammo alcohols as catalysts for the Baylis-Hillman condensation of aldehydes with methyl vinyl ketone the unexpected pressure effect on the reaction has been rationalized.37... 

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