Unsaturated aldehydes acylation

The most efficient intramolecular secondary processes competing with the acyl-alkyl diradical recombination in five-membered and larger cyclic ketones are hydrogen shifts resulting in the disproportionation of the diradical to either ketenes or unsaturated aldehydes [cf. (5) (4) (6)]. 

Acyl-AlkyI Diradical Disproportionations to Ketenes and Unsaturated Aldehydes... 

A one-pot procedure from aldehydes, through Wittig olefmation and a subsequent epoxidation, was also reported. Aldehydes could be converted into a,P,y,8-unsaturated N-acyl pyrroles, which were epoxidized in the same pot to give N-acyl pyrrole-substituted vinylepoxides [32]. 

The lithium enolate of the oc-silyl-substituted iron-acyl complex 19 reacts with aldehydes, however, products of the Peterson elimination process (E)- and (Z)-22 are usually isolat-ed22- 23,36.37 for t[1js anc other preparations of a,/t-unsaturated iron-acyl complexes see Section I.3.4.2.5.I.3.). 

Addition of A-mesityl benzimidazolyl carbene 720 to an a,/3-unsaturated aldehyde generates a homoenolate intermediate that undergoes an addition/acylation sequence with azomethine imine 719 to afford (3R, 5S, 6S )-177-pyrazolo[l,2- ]pyridazine-l,8(5//)-diones 721 with excellent diastereoselectivity. Compound 721 (Ar = R = Ph) treated with sodium hydoxide in methanol or benzylamine provided nearly quantitatively, ring-opened products 722a and 722b, respectively (Scheme 116) <2007JA5334>. 

A viable iron carbonyl-mediated reduction process converts acid chlorides and bromoalkanes into aldehydes [3, 6]. Yields are high, with the exception of nitro-benzoyl chloride, and the procedure is generally applicable for the synthesis of alkyl, aryl and a,(i-unsaturated aldehydes from the acid chlorides. The reduction proceeds via the initial formation of the acyl iron complex, followed by hydride transfer and extrusion of the aldehyde (cf. Chapter 8). 

Both above mentioned complex hydrides have been successfully used for the preparation of unsaturated aldehydes from unsaturated acyl chlorides (yields 48-71%) [1011] and for the synthesis ofp-nitrobenzaldehyde from p-nitroben-zoyl chloride [775, 7077], a reduction which could hardly be achieved by applying catalytic hydrogenation. 

V-Acylsaccharins prepared by treatment of the sodium salt of saccharin with acyl chlorides were reduced by 0.5 molar amounts of sodium bis(2-methoxyethoxy)aluminum hydride in benzene at 0-5° to give 63-80% yields of aliphatic, aromatic and unsaturated aldehydes [1108 Fair yields (45-58%) of some aliphatic aldehydes were obtained by electrolytic reduction of tertiary and even secondary amides in undivided cells fitted with platinum electrodes and filled with solutions of lithium chloride in methylamine. However, many secondary and especially primary amides gave 51-97% yields of alcohols under the same conditions [130]. 

Masakatsu Shibasaki of the University of Tokyo reports (J. Am. Chem. Soc. 2004,126, 7559) that use of a BINOL-derived catalyst with cumyl hydroperoxide enables the enantioselective epoxidation of unsaturated N-acyl pyrroles such as 7. The pyrroles 7, prepared from the precursor aldehydes such as 5 with the reagent 6, can be used directly, without further purification. 

Other examples of electrophilic toxic chemicals are aldehydes and ketones, especially unsaturated ones, acyl halides and cyanates. 

The acyl-alkv biradical obtained by ring-opening of a cyclic ketone is able lo undergo intramolecular disproportionation in one of two ways. A hydrogen atom may be transferred to the acyl radical from the position adjacent to the alkyl group, and this produces an unsaturated aldehyde (4.21). Alternatively, a hydrogen may be transferred to the alkyl radical from the position adjacent to the acyl group, and this results in the formation of a ketene (4.22). Many ketenes are labile, and the use of a nucleophilic solvent or addend. 

Certain unsaturated aldehydes may be converted to cyclic ketones by a related mechanism. The formyl group reacts with Rh(I) complexes to form an acyl-Rh hydride species, which undergoes intramolecular reaction with the olefinic linkage present in the same molecule (117a). Asymmetric induction is observed with a chiral diphosphine ligand (Scheme 53) (117b-d). Enantioselective cyclization of 4-substituted 4-pentanals into 3-substituted cyclopentanones in greater than 99% ee is achieved with a cationic BINAP-Rh complex. 

Co(III)] complexes. For example, the coupling of 3-halocholestanes (333) and Michael acceptors affords epimeric mixtures of the 3-homologated steroids (334). The electrochemical nucleophilic acylation of a, 3-unsaturated aldehydes, a,3-unsaturated ketones and a,(3-unsaturated nitriles with acyl anhydrides affords adducts (335) in moderate yields.226a-b Similarly, the reduction of N-methyloxazolinium salts (336) affords die A, O-acetal intermediates (337) which are readily hydrolyzed (Scheme 102).226c... 

Typically, oc,0-unsaturated esters, a,0-unsaturated aldehydes and a,0-unsaturated nitriles are poor acceptors for the Lewis acid catalyzed silylallylation procedure, but they are excellent acceptors for the complementary fluoride ion mediated allylation procedure (cf. Volume 4, Chapter 1.2, Section 1.2.2.1.7). Other suitable acceptors include 1,4-quinones,70 a,0-unsaturated acyl cyanides (162),718 silyl ot,0-enoates (163)71b and nitroalkenes (Scheme 26) 72 reduction (titanium(III) trichloride) of the intermediate nitronates arising from nitroalkene allylation affords y,8-enones (166). 

Not surprisingly, active M11O2 is able to oxidize unsaturated cyanohydrins, resulting in the generation of acyl cyanides. Interestingly, both the formation of the cyanohydrins by reaction of aldehydes with cyanide, and the hydrolysis of acyl cyanides with MeOH, resulting in the formation of methyl esters, can be carried out in situ with the MnC>2 oxidation. Thus, Corey et al. proved68 that aldehydes can be directly transformed into methyl esters by treatment with NaCN and active MnC>2 in a mixture of acetic acid and methanol. This represents a useful protocol for the oxidation of unsaturated aldehydes to esters. 

Nowick and Danheiser148 have explored a-cyclopropyl acyl silane generation from a-haloacyl silanes through McCoy reactions (Scheme 57) and via sulphur ylids (Scheme 58). Ylid species such as 24 were found to be stable in aprotic solvents in the presence of lithium salts, and were used for the cyclopropanation of a,/3-unsaturated aldehydes. 

Silyl enol ethers of acyl silanes have been used in Lewis acid-mediated Mukaiyama reactions with acetals. Treatment of the resulting /1-alkoxy acyl silanes with tetrabutylammonium hydroxide or tetrabutylammonium fluoride gave the corresponding a,/J-unsaturated aldehydes (Scheme 99)210. 

Enantioselective additions of a,f)-unsaturated 2-acyl imidazoles, catalyzed by bis(oxazolinyl)pyridine-scandium(III)triflate complex, were used for the asymmetric synthesis of 3-substituted indoles. The complex 114 was one of the most promising catalysts. The choice of acetonitrile as the solvent and the use of 4 A molecular sieves were also found to be advantageous. The 2-acyl imidazole residue in the alkylation products of u,(i-unsaturated 2-acyl imidazoles could be transformed into synthetically useful amides, esters, carboxylic acid, ketones, and aldehydes (Scheme 32) [105]. Moreover, the catalyst 114 produced both the intramolecular indole alkylation and the 2-substituted indoles in good yield and enantioselectivity (Scheme 33) [106]. The complex... 

Norbomanones experience a-cleavage on the side of the more highly substituted carbon when irradiated, the intermediate acyl radicals ultimately undergoing intramolecular C-H abstraction to generate unsaturated aldehydes.193,194 The... 

Intramolecular disproportionation of [1] could conceivably result in the formation of unsaturated aldehyde or ester. Both paths are well known to occur with cyclic alkanones (la). Abstraction of H by the acyl radical portion of [1] would produce alkenal [3] while abstraction of by the alkyl radical portion of [1] would produce ketene [4] which may be efficiently trapped in nucleophilic alcoholic solvents to yield ester [5]. The intramolecular nature of alkenal formation is supported by deuterium labeling experiments (5), while the intramolecular nature of ketene formation is supported by (a) deuterium labeling experiments (6,7), and (b) the observed decrease in ketene formation with decreasing ring size (8). 

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