Ylide compounds aldehyde derivation

Another chiral vinylogous urethane, 677, played a central role in the synthesis of (- )-652 by Lhommet and co-workers (Scheme 90) 494). This compound, prepared from (/ )-a-methylbenzylamine (678) (495), was diastereoselectively hydrogenated over platinum oxide to give the amino-ester 679 (de >95%). More significantly, methylation of the anion of 679 under conditions of kinetic control afforded 680 (de ca 98%) in 33% overall yield from the chiral amine 496). Wittig reaction of the aldehyde derivative 681 with the stabilized ylide l-(triphenylphosphoranylidene)-2-heptanone yielded 682 (90%) as a 4 1 mixture of E and Z isomers. When this product... 

Previous syntheses of terminal alkynes from aldehydes employed Wittig methodology with phosphonium ylides and phosphonates. 6 7 The DuPont procedure circumvents the use of phosphorus compounds by using lithiated dichloromethane as the source of the terminal carbon. The intermediate lithioalkyne 4 can be quenched with water to provide the terminal alkyne or with various electrophiles, as in the present case, to yield propargylic alcohols, alkynylsilanes, or internal alkynes. Enantioenriched terminal alkynylcarbinols can also be prepared from allylic alcohols by Sharpless epoxidation and subsequent basic elimination of the derived chloro- or bromomethyl epoxide (eq 5). A related method entails Sharpless asymmetric dihydroxylation of an allylic chloride and base treatment of the acetonide derivative.8 In these approaches the product and starting material contain the same number of carbons. 

The 3-oxo-2-pyrazolidinium ylides 315, easily available by reaction of the corresponding pyrazolidin-3-one with aromatic aldehydes, function as 1,3-dipoles in cycloaddition reactions with suitable alkenes and alkynes to provide the corresponding products. When unsymmetrical alkynes are used, mixtures of both possible products 316 and 317 are usually obtained (Equation 45). The regioselectivity of cycloadditions of the reaction with methyl propiolate is influenced by the substituents on the aryl residue using several 2,6-di- and 2,4,6-trisubstituted phenyl derivatives only compound 316 is formed <2001HCA146>. Analogous reactions of 3-thioxo-l,2-pyrazolidinium ylides have also been described <1994H(38)2171>. 

Sulfur ylides are a classic reagent for the conversion of carbonyl compounds to epoxides. Chiral camphor-derived sulfur ylides have been used in the enantioselective synthesis of epoxy-amides <06JA2105>. Reaction of sulfonium salt 12 with an aldehyde and base provides the epoxide 13 in generally excellent yields. While the yield of the reaction was quite good across a variety of R groups, the enantioselectivity was variable. For example benzaldehyde provides 13 (R = Ph) in 97% ee while isobutyraldehyde provides 13 (R = i-Pr) with only 10% ee. These epoxy amides could be converted to a number of epoxide-opened... 

The ylide obtained from (methyl)triphenylphosphonium bromide reacts with morpholine derivatives 597 to give phosphonium salts 598 which upon treatment with -butyllithium are converted to new ylides 599. In a reaction with aldehydes, ylides 599 form iV-(l,3-disubstituted allyl)-morpholines 602 (Scheme 94) <1996AQ138>. Another less common nucleophile that can be used for substitution of the benzotriazolyl moiety in Af-(a-aminoalkyl)benzotriazoles is an adduct of iV-benzylthiazolium salt to an aldehyde which reacts with compounds 597 to produce adducts 600. Under the reaction conditions, refluxing in acetonitrile, salts 600 decompose to liberate aminoketones 601 <1996H(42)273>. 

Ylides forming from the thermolysis of compound 59 (R1, R2 = Me, R3 = Ar, R4 = OMe) reacted also with dimethyl acetylenedicarboxylate (DMAD) or diethyl azodicarboxylate (DEAD) <2003TL5029> in the presence of aldehydes, quinones <2001TL2043>, or ketones <20020L2821, 20000L3501> to give 2,5-dihydrofuran derivatives, for example, 67 (Rs = Me, Et). 

The difluoromethylene ylides react with carbonyl derivatives (aldehyde, lactone) to afford gem-difluoromethylene compounds.They are generated starting from halogenodifluoromethane with triphenylphosphine (or trisaminophosphine) or starting from zinc and a phosphonium salt (or a phosphine oxide)." ° ... 

These compounds come from methylenation reactions of the corresponding carbonyl derivative by means of an ylide. Several experimental conditions have been described. In most cases, CF2Br2 and HMPT (hexamethyl phosphorotriamide) are employed. The reaction occurs with aldehydes as well as with ketones in the furanose and pyranose series. The reaction can also be performed with lactones the fluoromethyl group is then introduced in the anomeric position. With these substrates, the Julia olefmation, which uses difluoromethyl sulfone, has also been reported to be an efficient method. Some examples of these reactions are shown in Figure 6.24. 

The other stereoselective synthesis/281 shown in Scheme 8, foresees conversion of Boc-L-Asp-OtBu 20 into the related (3-aldehyde 22 via the Weinreb amide 21 and its reduction with diisobutylaluminum hydride (DIBAL-H). Wittig condensation of 22 with the ylide derived from (3-carboxypropyl)triphenylphosphonium bromide using lithium hexamethyldisilaza-nide at —78 to 0°C, produces the unsaturated compound 23 which is catalytically hydrogenated to the protected L-a-aminosuberic acid derivative 24. Conversion of the co-carboxy group into the 9-fluorenylmethyl ester, followed by TFA treatment and reprotection of the M -amino group affords Boc-L-Asu(OFm)-OH (25). 

In an effort to explain these atypical reactivity patterns, a mechanistic postulate based on direct electrostatic activation (DEA) was proposed (Scheme 3.8). Indeed, the zwitterionic iminium ions derived from catalyst 10 and a,/i-un saturated aldehydes enable both iminium geometry control and direct electrostatic activation of the approaching sulfonium ylides. The combination of geometric and electronic control seems to be essential for enantio- and diastereocontrol in the formation of the desired cyclopropyl compound. 

The reaction of ylides with carbodiimides usually produces linear 1 1 adducts. The adducts derived from DMSO and carbodiimides undergo a facile reaction with primary alcohols to give an aldehyde (Moffat oxidation). With phenols and carboxyhc acids, alkylation products and esters, respectively, are formed. The oxidation proceeds under mild conditions and can be applied to sensitive compounds. Primary alcohols are oxidized solely to aldehydes without the formation of even trace amounts of carboxylic acids. The carbodiimide adducts generated from DMSO or the dimethylseleniumoxide " adducts have structure 369 (X = S, Se). 

---