Unsaturated Aldehydes and Ketones

Ficini, S. Falou, A.-M. Touzin, and J. d Angelo, Tetrahedron Letters, 1977, 3589. 

Reagents i, CsHsN.HCrOaCI ii, LiN(CHMe2)2 ii, MeSSMe iv, HgCla, CaCOa. THF, HjO 

Nakamura, T. Taguchi, and H. Takei, Chem. Letters, 1977, 345. 

A full paper on the preparation of 5-alkoxy-aj8-unsaturated aldehydes from 1-trimethylsilyloxybuta-1,3-diene and acetals has been published/  

Vilsmeier formylation of various 2-methylhexa-l,3.5-trienes proceeds smoothly to give the corresponding 3-methyl-2,4,6-trienal in good yield. 

FIGURE 20.19 Synthesis of enals and enones by aldol condensation. 

Show how you would disconnect each of the following enones to a dicarbonyl compound  

Conjugated unsaturated aldehydes are hydrogenated quantitatively to saturated aldehydes with cobalt catalyst under hydroformylation conditions. 

A number of unsaturated aldehydes were contacted with stoichiometric amounts of cobalt hydrocarbonyl at normal conditions by Orchin et al. [260], (see table 16). 

In these cases, the reaction is exclusively hydrogenation. The reason for the absence of hydroformylation lies, according to Orchin et al,y in the formation of a 7c-allyl type complex intermediate, which reacts according to scheme 3 (see also the section on dienes). 

Analogous to conjugated unsaturated aldehydes, conjugated unsatur-ted ketones react after the above scheme to saturated ketones [35] (table 17). 

Conjugated unsaturated aldehydes and ketones may be hydroformylated in good yield through their acetals or ketals (see also the section on imsatur-ated ethers). 

Unsaturated Aldehydes and Ketones.— -Hydroxycarbonyl compounds are commonly-considered precursors to o -unsaturated aldehydes and ketones. However, simple aldol reactions often may not be appropriate for the construction of particular enones. Isoxazolines offer ever more attractive routes to hydroxy-ketones, and hence enones, as their chemistry continues to be explored. The 

Reagents i. Nal.MejCO ii, AgNOi.EhO iii, Et3NjMi iC H4NCO iv, H2.W-2 Raney nickel v, MeSOiQ.EtjN 

Reagents i, Bu OK.DMSO ii, AiCHO iii. Hi.PtOj iv, Af-tosyl-L-prolyl chloride, pyridine v. NaBH4,MeOH vi, Ac0H,H20 vii, H2,Pd/C 

The Wittig reaction can oifer a powerful alternative to the aldol reaction for construction of a -unsaturated carbonyl compounds. (2,2-Diethoxyethylidene)-triphenylphosphorane shows very high stereoselectivity in reactions with aldehydes to give (Z)-ap-unsaturated aldehyde acetals, which may readily be cleaved to the less stable (Z)-isomer of the enal [equation (21)]. Alkenyl fluoromethyl 

3-Dicarbonyl compounds continue to attract attention as precursors to unsaturated ketones. Readily prepared trimethylsilyl enol ethers react well with alkyl-lithiums, but poorly with Grignard or dialkylcopper-lithium reagents, to give enones [equation (23)]. a-Oxoketene thioacetals undergo chemoselective 

Unsaturated Aldehydes and Ketones.—Irradiation of oxygenated solutions of T7 -allylpalladium complexes leads to unsaturated carbonyl compounds in modest yield. Oxidation of (steroidal) 7r-allylpalladium complexes can also be carried out using chromium trioxide in dimethylformamide containing a trace of sulphuric acid.  

3-Ketosteroids are smoothly oxidized to the l,4-dien-3-ones by benzene seleninic anhydride. Barton and his group have now made this reaction catalytic in selenium by developing the use of iodylarenes for the in situ oxidation of diphenyldiselenide to the anhydride. m-Iodylbenzoic acid was chosen to aid the isolation of the product and the recovery of the aryl iodide. 

Z-2-(Trimethylsilyloxy)vinyl-lithium shows promise as a nucleophilic acetaldehyde equivalent in condensation with aldehydes and ketones, since the adducts hydrolyse very readily to unsaturated aldehydes [equation (23)]. In another 

In designing routes to enones, the principle of isomerization of intermediates to the thermodynamically more stable isomer should not be ignored. Applying this principle, synthesis of 2-alkylcyclopentenones can become much more straightforward. Either an enamine-controlled aldol condensation [equation (25)], or a modified aldol using the readily prepared a- 

The super-acidic resin Nafion-H is recommended over other resins as catalyst for the Ruppe rearrangement of a-acetylenic alcohols to enones. °  

Unsaturated Aldehydes and Ketones. - A five-step procedure for the synthesis of cyclic 3-nitroalkenones from the 

An arsonium salt (23), has been used in a reaction closely 

ReagtrtfS i, Me CuLi, /, TMSCl, iii. mepba i iv, EtjNHf v.TBDMSCI. imidazole, vi.Ph-PfOCHLiOMe, vii, NaH viii, HF, MeCN 

The palladium catalysed carbonylative cyclisation of (i)-iodoalkenes normally gives exo-methylene products however in a methanol-containing reaction mixture the initially formed alkyl palladium species will add a second equivalent of carbon monoxide to give keto-ester products [equation (27)].  

Palladium catalysis is also crucial to the success of enone preparation by the reaction of aromatic acid chlorides with 

Unsaturated Aldehydes and Ketones. - Trimethylsilylenol ethers derived from either aldehydes or ketones are oxidised, in good yields, to enals or enones respectively, by treatment with diallyl carbonate in the presence of catalytic palladium(0). Acetonitrile is the required solvent if allylation is to be avoided 

Chromium (II) salts have been found to reduce a-acetylenic 

Several protocols for the preparation of unsaturated ketones by the reaction of alkenyl- or alkynyl- metal derivatives with esters or with acid chlorides have been reported. Thus a,0-unsaturated 

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 

0-fuctionalisation uses silicon chemistry for the elaboration of the 0-side chain. This requires the preparation of a 0-trimethylsilylmethyl enone by conjugate addition of trimethylsilylmethyImagnesium chloride and oxidation, to give the key intermediate (19). The 0-substituent is then elaborated by 

Base-induced fragmentations of y-hydroxyammonium compounds can give poor yields when the product is an aldehyde. However, flash thermolysis is now reported to give good yields of unsaturated aldehydes [equation (20)]. 

The three-carbon extension of aldehydes to /3,y-unsaturated aldehydes by the Wittig reagent (52) has been described Wittig reactions of the ylide (53) give protected /Sj-y-unsaturated ketones in good yield [equation (21)].  

TT-Allylnickel halides react with 2-pyridylcarboxylates as acylating agents in a new mild process leading to /3,y-unsaturated ketones/ and the oxidative rearrangement of tertiary cyclopropylcarbinols provides a further route to /3,y-unsaturated ketones, if only in moderate yields [equation (22)]. 

An interesting, if highly specific, y,5-unsaturated aldehyde preparation uses an irreversible Claisen rearrangement to trap the product of an unfavourable Cope rearrangement [equation (24)].  

An improved method for the preparation of 2-alkenals from the corresponding saturated aldehydes centres on the bromination of the enol acetate. Treatment with sodium hydroxide and a phase-transfer catalyst in the presence of methanol completes the sequence [equation (25)].  

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Aldol condensation offers an effective route to a p unsaturated aldehydes and ketones These compounds have some interesting properties that result from conjugation of the carbon-carbon double bond with the carbonyl group As shown m Figure 18 6 the rr systems of the carbon-carbon and carbon-oxygen double bonds overlap to form an extended rr system that permits increased electron delocalization... 

FIGURE 18 7 Nucleophilic addition to a p unsaturated aldehydes and ketones may take place either in a 1 2 or 1 4 manner Direct addition (1 2) occurs faster than conjugate addition (1 4) but gives a less stable product The product of 1 4 addition retains the carbon-oxygen double bond which is in general stronger than a carbon-carbon double bond... 

The preparation and some synthetic applications of lithium dialkylcuprates were described earlier (Section 14 11) The most prominent feature of these reagents is then-capacity to undergo conjugate addition to a p unsaturated aldehydes and ketones... 

P carbon atom of an a 3 unsatu rated carbonyl compound is elec trophilic nucleophiles especially weakly basic ones yield the prod ucts of conjugate addition to a 3 unsaturated aldehydes and ketones... 

Dijbner-von Miller Synthesis. A much less violent synthetic pathway, the Dn bner-von Miller, uses hydrochloric acid or 2inc chloride as the catalyst (43). As in the modified Skraup, a,P-unsaturated aldehydes and ketones make the dehydration of glycerol uimecessary, and allow a wider variety of substitution patterns. No added oxidant is required. With excess aniline the reaction proceeds as follows ... 

Xanthates have been added to activated double bonds, eg, acryhc derivatives and a,P-unsaturated aldehydes and ketones (59—61) ... 

The procedure described illustrates a general method for the preparation of o ,j3-unsaturated aldehydes and ketones from the enol ethers of 3-dicarbonyl compounds. 

The diminished tt electron density in the double bond makes a,p-unsaturated aldehydes and ketones less reactive than alkenes toward electrophilic addition. Electrophilic reagents—bromine and peroxy acids, for example—react more slowly with the carbon-carbon double bond of a,(3-unsaturated carbonyl compounds than with simple alkenes. 

Conjugate Nucleophilic Addition to a, /3-Unsaturated Aldehydes and Ketones 727... 

Both primary and secondary amines add to a /S-unsaturated aldehydes and ketones to yield /3-amino aldehydes and ketones rather than the alternative imines. Under typical reaction conditions, both modes of addition occur rapidly. But because the reactions are reversible, they generally proceed with thermodynamic control rather than kinetic control (Section 14.3), so the more stable conjugate addition product is often obtained to the complete exclusion of the less stable direct addition product. 

A novel and versatile method for preparing polymer-supported reactive dienes was recently developed by Smith [26]. PS-DES (polystyrene diethyl-silane) resin 28 treated with trifluoromethanesulfonic acid was converted to a polymer-supported silyl triflate 29 and then functionalized with enolizable a,jS-unsaturated aldehydes and ketones to form silyloxydienes 30 and 31 (Scheme 4.4). These reactive dienes were then trapped with dienophiles and the Diels Alder adducts were electrophilically cleaved with a solution of TFA. 

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