Aliphatic enals

This reaction is equally amenable to enals with both aliphatic and aromatic P-substituents, althongh the formation of substitnted cyclohexanes (from analogous enals) proceeds with rednced enantioselectivity (Scheme 12.51) [92], You and co-workers have shown that the same reaction is also promoted by triazolinm salts derived from camphor in excellent enantioselectivity (95-99% ee) [93]). 

Hetero Pauson-Khand reactions with an aldehyde or ketone component have been shown to afford synthetically versatile y-butyrolactones. Buchwald [50] and Crowe [51] independently showed that aliphatic enones and enals react with CO under Cp2Ti(PMe3)2 mediation (Scheme 11). CO insertion and thermal (or oxidative) decomposition gave diastereomerically pure bicyclic y-butyrolactones and stable Cp2Ti(CO)2. Imines did not react under the reaction conditions. 

It has been noted that when the aldol condensation is conducted on simple aliphatic aldehydes, such as octanal, in the presence of an alkylating agent and a quaternary ammonium salt the 2-position is alkylated and the alk-3-enal is isolated (Scheme 6.14) [16]. In the absence of the quaternary ammonium salt, the normal aldol adduct is formed with no alkylation. It is noteworthy that in the presence of epichlorhydrin the dienyl ether is formed. 

Various aldehydes 184 and alcohols have been shown to be competent in the redox esterification of unsaturated aldehydes in the presence of the achiral mesityl triazo-lium pre-catalyst 186. Both aromatic and aliphatic enals participate in yields up to 99% (Table 13). Tri-substituted enals work well (entry 3), as do enals with additional olefins present in the substrate (entries 4 and 7). The nucleophile scope includes primary and secondary alcohols as well as phenols and allylic alcohols. Intramolecular esterification may also occur with the formation of a bicyclic lactone (entry 8). 

The ruthenium-catalyzed direct addition of saturated aliphatic alcohols to non-activated alkynes remains a challenge. Only ally alcohol has been successfully involved in the intermolecular addition to phenylacetylene to produce an ether and the enal resulting from Claisen rearrangement (Equation 10.7) [24]. Thus, in refluxing toluene, in the presence of a catalytic amount of RuCl(tris(pyrazolyl) borate) (pyridine)2, a 1 1 mixture of ally P-styryl ether and 2-phenylpent-4-enal was obtained in 72% overall yield. 

Nitriles.1 This sulfilimine reacts with aldehydes to give the corresponding nitriles (equation I). The reaction with aliphatic a,/l-enals results in 2-cyanoaziri-dines. 

Recently, Bode et al. were able to demonstrate that the products formed after generation of the homoenolate equivalents 67 are determined by the catalytic base [64]. Strong bases such as KOt-Bu led to carbon-carbon bond-formation (y-butyrolactones), while weaker bases such as diisopropylethylamine (DIPEA) allowed for protonation of the homoenolate and the subsequent generation of activated carboxylates. The combination of triazolium catalyst 72 and DIPEA in THF as solvent required no additional additives and enabled milder reaction conditions (60 °C), accompanied by still high conversions in the formation of saturated esters out of unsaturated aldehydes (Scheme 9.21). Aliphatic and aromatic enals 62, as well as primary alcohols, secondary alcohols and phenols, are suitable substrates. a-Substituted unsaturated aldehydes did not yield the desired products 73. 

Asymmetric allylboration of RCHO. (S)-l reacts with aliphatic or aryl aldehydes or with a,p-enals to form homoallylic alcohols in 92-97% ee and 80-92% chemical yield. The chemical and optical yields are higher than those obtained with B-allyldiisopinocamphenylborane (14,12), with allylboronates modified with tartrates, or with B-allyltrimethylsilylboronates. The high asymmetric induction is believed to result from steric effects rather than electronic effects. 

Reaction of RCHO with CJfCH=CHCH1Cl. This reaction can be regio-selective and f/ireo-selective when mediated by Sn and Al. The reaction of benz-aldehyde with cinnamyl chloride provides the anfi-homoallylic alcohol as the only detectable product. This diastereoselectivity obtains generally with aliphatic or aromatic aldehydes. The reaction with enals under the same conditions provides only the 1,2-adducts, again with anti-selectivity (equation I). The reaction of 2-phenylpropanal with 1 provides a mixture of homoallylic alcohols in the ratio 3 1, with anti-selectivity at the C—C bond formed in the reaction (equation II). 

Iriye R, Toya T, Makino J, Aruga R, Doi Y, Handa S, Tanaka H (1988) Synthesis of aliphatic dienedials, w-hydroxydienals, a>-hydroxy-2-alkenals, vinylke-tones, an enon-enal and aliphatic dienediones. Agric Biol Chem 52 989-996... 

The use of a relatively soluble base such as CS2CO3 allows good product yield. No products are formed via carbopalladation. Therefore the reaction is considered to occur on a dienolate anion generated from the enal to give an aryl(7r-allyl)palladium intermediate. The regioselectivity seems to be determined in the reductive elimination of the product. Treatment of aliphatic aldehydes with aryl bromides brings about aldol condensation followed by y-aryla-tion to afford 2 1 coupling products (Eq. 27). Note that y-arylation products are also produced in the arylation of a tin-masked dienolate [65,66]. 

This chiral catalyst was then found to effect aldol reactions of aldehydes with the silyl enol ether of S-cthyl propancthioatc (equation II). In this case dibutyltin diacetatc is somewhat superior to tributyltin fluoride as the cocatalyst. With this chiral promotor, chemical yields arc high, and only the syn-aldol is formed in >98% cc. This high stereoselectivity obtains with aliphatic and aromatic aldehydes and a, /3-enals. 

CHO —coon. This oxidation can be effected with NaClO if a scavenger is also present to reduce the HOCI formed to HO and Oj. For this piiiposc either 3S% UtO or DNfSO is more useful than sulfamic acid, H-NSC),H. 2-methyl-2-buiene, or resorcinol. Reactions with NaCIOj-H Oj are canted out usually in aqueous acetuniiHle, those with DMSO, in aqueous DMiiO. Yields of >90% can be obtained with aliphatic and aromatic aldehydes as well as the a.fS-enalS- Only chlorinated products are obtained from aldehydes containing isolated double bonds. 

Aldehyde olefination CHjReOs (1) is an efficient catalyst for condensation of aldehydes with a diazoalkane and a phosphine to form an alkene and a phosphine oxide. The actual catalyst may be CH3Re020PR3. The reaction is applicable to aliphatic and aromatic aldehydes and also to enals. Some cycloketones undergo this olefination but in only moderate yield. 

Some attempts to use aliphatic alcohols as nucleophiles in the enantioselec-tive conjugate addition to enals have been carried out, but with no success with regard to the stereochemical control (Scheme 3.29). For example, the conjugate addition of methanol to several aliphatic enals using axially chiral amines derived from BINOL as catalysts proceeded with enantioselectivities around 50% ee and also a 31c-catalyzed intramolecular reaction leading to the formation of the tetrahydropyrane skeleton has been reported to proceed with 57% ee. 

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