2-Cyclohexenone aluminum hydrides

Ethoxy-2-cyclohexenone is a useful intermediate in the synthesis of certain cyclohexenones. The reduction of 3-ethoxy-2-cyclohexenone with lithium aluminum hydride followed by hydrolysis and dehydration of the reduction product yields 2-cyclo-hexenone. Similarly, the reaction of 3-ethoxy-2-cyclohexenone with Grignard reagents followed by hydrolysis and dehydration of the addition product affords a variety of 3-substituted 2-cyclo-hexenones. ... 

Lithium aluminum hydride, in reduction of 3-ethoxy-2-cyclohexenone to 2-cyclohexenone, 40, 14 Lithium ethoxide in condensation of benzaldehyde with tripbenylcin-namylphosphonium chloride to form 1,4-diphenyl-l, 3-butadiene,... 

For the more reactive nucleophiles, where addition is essentially irreversible, whether 1,2-addition or 1,4-addition occurs depends on the relative rates of addition to the two electrophilic sites, the carbonyl carbon and the /3-carbon. Lithium aluminum hydride usually gives predominantly 1,2-addition and provides a useful way to reduce the carbonyl group of an a,/3-unsaturated compound. Sodium borohydride, on the other hand, often gives a mixture of 1,2-addition and the completely reduced product, where 1,4-addition followed by 1,2-addition has occurred. Thus, the reaction of 2-cyclohexenone with lithium... 

Unfortunately, the complete enantiofacial differentiation of cyclohexenone (eq 7) appears to be an isolated case, as reaction with 3-methylcyclohexenone afforded the corresponding (S)-cyclohexanol in only 28% ee. In the absence of a general trend for the outcome of these reductions, the scope of this method seems limited at this point, as opposed to (S)-BINAL-H mediated reductions (see Lithium Aluminum Hydride and subsequent articles). 

The first chiral aluminum catalyst for effecting asymmetric Michael addition reactions was reported by Shibasaki and coworkers in 1986 [82], The catalyst was prepared by addition of two equivalents of (i )-BINOL to lithium aluminum hydride which gave the heterobimetallic complex 394. The structure of 394 was supported by X-ray structure analysis of its complex with cyclohexenone in which it was found that the carbonyl oxygen of the enone is coordinated to the lithium. This catalyst was found to result in excellent induction in the Michael addition of malonic esters to cyclic enones, as indicated in Sch. 51. It had previously been reported that a heterobimetallic catalyst prepared from (i )-BINOL and sodium and lanthanum was also effective in similar Michael additions [83-85]. Although the LaNaBINOL catalyst was faster, the LiAlBINOL catalyst 394 (ALB) led to higher asymmetric induction. 

Inspired by the bimetallic catalyst developed by Shibasaki and coworkers with 2 1 complexes of BINOL with aluminum, Manickam and Sundararajan prepared 2 1 complexes of the aminodiol 420 with aluminum [87,88]. Reaction of malonate esters with cyclopentenone or cyclohexenone results in asymmetric induction of at least 90 % ee with dibutyl malonate, as detailed in Sch. 57. A catalyst prepared by the reaction of 2 equiv. diol 419 with lithium aluminum hydride was found to result in asymmetric induction for the reaction of cyclohexenone with malonate 390d similar to that observed with the catalyst derived from 420 and from BINOL, although the rate was slightly slower. 

Many of the naturally occurring ochtodanes have a double bond in the ring, and the most direct way to 5,5-dimethyl-2-cyclohexenone (728) is from the enol ether of dimedone by lithium aluminum hydride reduction. " The cyclohexenone can then be used directly to introduce a C2 unit it was also reduced catalytically to the previously mentioned 3,3-dimethylcyclohexanone. Treatment of the ozonolysis product from 3-carene (277) with sodium ethoxide also led to a ketone, 729, that might be a useful starting material. ... 

The stereoselectivity of the hydride reduction of conjugated cyclohexenones has also been subjected to close examination from both experimental and theoretical viewpoints. Much of the work has involved polycyclic systems, e.g.. steroids which have little conformational flexibility and in which axial and equatorial directions of approach can be clearly defined. With small" hydride donors, these substrates show an even clearer preference for axial attack than the corresponding cyclohexanones. For examples involving reductions with lithium aluminum hydride and sodium borohydride, see Table 10. 3/(-Acetylcholest-5-en-7-one and cholest-2-en-l-one are notable in that the analogous saturated substrates are attacked from the equatorial direction115 l16. The reduction of 17/i-hydroxy-4-androsten-3-one (testosterone) to 4-androstene-3/1,17/j-diol with d.r. 90 10 can be compared with the sodium borohydride reduction of 17/i-hy-droxyandrostan-3-one (dihydrotestosterone) to androstane-3/ ,17/ -diol with d.r. 81 19 (see p 4030). 

The paper reports preparation of two new copper hydride complexes. The lithium complex (1) is prepared from CuBr and 2 equiv. of lithium trimethoxy-aluminum hydride (cf. 5, 168) the sodium complex (2) is prepared from CuBr and 1 equiv. of sodium bis(2-methoxyethoxy)aluminum hydride. Both complexes are useful for selective reduction of the double bond of conjugated cnones 1 is more efficient for reduction of cyclohexenones and 2 is more efficient for reduction of acyclic enones. Aldehydes, ketones, and halides are also reduced nitrile and ester units are inert. The effective stoichiometry of both reagents is consistent with the structures LiCuHj and NaCuHs, but complex 1 is clearly different from a reagent assigned the structure LiCuHa by Ashby et al. ... 

Lithium aluminum hydride in reduction of 3-ethoxy-2-cyclohexenone to... 

In Chapter 19 (Section 19.2), lithium aluminum hydride and sodium borohydride reacted with ketones or aldehydes via acyl addition to reduce the carbonyl to the corresponding alcohol. This reaction is complicated by the presence of a conjugating n-bond. When cyclohexenone reacts with LiAlH4, the product is a mixture of cyclohexenol (66) and cyclohexanol (67). Cyclohexenol results from 1,2 addition of the hydride, but 67 results from 1,4 addition and 1,2 addition. 

---