Sterically hindered carbonyl

X0 to hydroxy compounds. Lower temperatures favor ketone formation and sterically hindered carbonyls, such as 2-thienyl t-butyl ketone, are not reduced. The sensitivity of desulfurization to steric factors is evident by the failure to desulfurize 2,5-di-i-butyl-3-acetylthiophene. The carbonyl groups of both aldehydes and ketones can be protected by acetal formation, as particularly cyclic acetals are stable during desulfurization in methanol at room temperature. " The free aldehydes give primary alcohols on desulfurization. Another method to obtain only keto compounds is to oxidize the mixtures of ketone and secondary alcohol with CrOs after the desulfurization. - Through the desulfurization of 5,5 -diacetyl-2,2, 5, 2"-terthienyl (228), 2,15-hexadecandione (229) has been obtained, which... 

Thus, various kmds of bases are effective in inducing the Henry reaction The choice of base and solvent is not crucial to carry out the Henry reaction of simple nitroalkanes v/ith aldehydes, as summarized in Table 3 1 In general, sterically hindered carbonyl or nitro compounds are less reactive not to give the desired ni tro-aldol products in good yield In such cases, self-condensation of the carbonyl compound is a serious side-reaction Several mochfied procedures for the Henry reaction have been developed... 

Other reagents used for the preparation of lactones from acid anhydrides are lithium borohydride [1019], lithium triethylborohydride (Superhydride ) [1019] and lithium tris sec-butyl)borohydride (L-Selectride ) [1019]. Of the three complex borohydrides the last one is most stereoselective in the reduction of 3-methylphthalic anhydride, 3-methoxyphthalic anhydride, and 1-methoxynaphthalene-2,3-dicarboxylic anhydride. It reduces the less sterically hindered carbonyl group with 85-90% stereoselectivity and is 83-91% yield [1019]. 

A pretty good diastereocontrol was achieved in the six-membered ring cyclization of 47, where diethylaluminium chloride and a catalytic amount of CuBr2 SMe2 were used to promote the internal attack of the Reformatsky centre to the sterically hindered carbonyl unit to give 48a and 48b (equation 32)108. 

Bellus and co-workers100 have obtained relatively stable dichlorooxiranes (55) by reaction of chloroform with a sterically hindered carbonyl group. 

Although the remaining steps required for the conversion of 463 to haemanthidine (382) were conceptionally straightforward, it was an experimentally difficult task owing to the poor stereoselectivity encountered in the reduction of the neopentyl ketone function at C-l 1. Moreover, the more forcing conditions required in some experiments to effect the reduction of the sterically hindered carbonyl function at C-ll resulted in an internal Cannizzaro hydride transfer process that produced nortazettine (467). The best results were eventually ob-... 

Sterically hindered carbonyls react more slowly (if at all). 

The RuCl2() -C6H6) 2/(R,S)-norephedrine/KOH catalyst system shows high chemo- and enantioselectivities in the reduction of 4-oxoisophorone in 2-propanol. Reduction of the sterically hindered carbonyl group is preferred over that of the less-hindered group (94 4) to give (R)-4-hydroxyisophorone in 97% e.e. as the major product (Eq. 2.37) [310]. No saturation of the double bond occurs. 

Barton, D. H. R., Ives, D. A. J., Thomas, B. R. A Wolff-Kishner reduction procedure for sterically hindered carbonyl groups. J. Chem. Soc., Abstracts 1955, 2056. 

A different side reaction may occur when a Grignard reagent reacts with a sterically hindered carbonyl compound that possesses an a-hydrogen. Suggest what may be the transition state for this reaction, and so suggest what would be the products. 

Acidic hydrolysis of the acetal group in 103 was attempted but this also lead to slow ringopening of the oxazoline. Quatemisation of the oxazoline 103 with methyl iodide followed by base hydrolysis was also problematic, giving only the amide 115 which resisted further hydrolysis under these conditions due to the sterically hindered carbonyl group. However, treatment of the quatemized oxazoline or amide 115 with KOH in wet DMSO provided the desired acid which was... 

Compound 37 contains a sterically hindered carbonyl. The Wittig reaction can be slow in such systems and/or give poor yields. Is this a problem here ... 

Trimethylaluminium in hexane added to a soln. of 2 eqs. 2,6-di-/er/-butyl-4-methyl-phenol as bulky electrophile in toluene, the mixture stirred at room temp, for 1 h, cooled to —78°, 0.5 eqs. carvone added, after 5 min the mixture treated via cannula with 1 eq. Li-hydrido-/ r/-butyIdiisobutyIaluminate in ether, stirred for 15 min, then poured into 10% HCl 5-isopropenyl-2-methylcyclohexanone. Y 93%. Enones with less sterically hindered carbonyls were more susceptible to 1,2-reduction. F.e.s. K. Nonoshita et al.. Bull. Chem. Soc. Japan 61, 2241-3 (1988). 

However, with slower-reacting and sterically hindered carbonyl compounds, the organoborane reduction may take an alternate pathway involving a prior dehydroboration process (Eqs. 4.18, 4.19) [11]. 

In view of these results it is not surprising that even more sterically hindered carbonyl derivatives of Rf are also not accessible (22), An attempted synthesis of (Rf)2C0 from RpLi and dimethyl carbonate gave the methyl ester of 2,4,6-tris(trifluoromethyl)benzoic acid instead (25% yield). Similarly, treatment of RpLi with oxalyl dichloride did not yield the desired benzil derivative. In this reaction a 45% yield of 2,4,6-tris(trifluoromethyl ) -2-oxoethanoic acid, RfC(0)C00H, was obtained (22), All these experiments clearly demonstrate that in organic Rf chemistry steric hindrance is an important factor guiding the reactivity of various substrates. 

---