Hydroxyalkylation with Carbonyl Compounds

A-Substituted pyrroles, furans and dialkylthiophenes undergo photosensitized [2 + 2] cycloaddition reactions with carbonyl compounds to give oxetanes. This is illustrated by the addition of furan and benzophenone to give the oxetane (138). The photochemical reaction of pyrroles with aliphatic aldehydes and ketones results in the regiospecific formation of 3-(l-hydroxyalkyl)pyrroles (e.g. 139). The intermediate oxetane undergoes rearrangement under the reaction conditions (79JOC2949). 

In this section alkylation, Michael additions, hydroxyalkylation (reaction with carbonyl compounds), aminoalkylation, acylation and some other reactions of a-sulphinyl carbanions will be discussed. 

Reaction of the carbanion of chloromethyl phenyl sulphoxide 409 with carbonyl compounds yields the corresponding 0-hydroxy adducts 410 in 68-79% yield. Each of these compounds appears to be a single isomer (equation 242). Treatment of adducts 410 with dilute potassium hydroxide in methanol at room temperature gives the epoxy sulphoxides 411 (equation 243). The ease of this intramolecular displacement of chloride ion contrasts with a great difficulty in displacing chloride ion from chloromethyl phenyl sulphoxide by external nucleophiles . When chloromethyl methyl sulphoxide 412 is reacted with unsymmetrical ketones in the presence of potassium tcrt-butoxide in tert-butanol oxiranes are directly formed as a mixture of diastereoisomers (equation 244). a-Sulphinyl epoxides 413 rearrange to a-sulphinyl aldehydes 414 or ketones, which can be transformed by elimination of sulphenic acid into a, 8-unsaturated aldehydes or ketones (equation 245). The lithium salts (410a) of a-chloro-/ -hydroxyalkyl... 

Samarium(II) iodide also allows the reductive coupling of sulfur-substituted aromatic lactams such as 7-166 with carbonyl compounds to afford a-hydroxyalkylated lactams 7-167 with a high anti-selectivity [74]. The substituted lactams can easily be prepared from imides 7-165. The reaction is initiated by a reductive desulfuration with samarium(ll) iodide to give a radical, which can be intercepted by the added aldehyde to give the desired products 7-167. Ketones can be used as the carbonyl moiety instead of aldehydes, with good - albeit slightly lower - yields. 

In 1968 Peterson published his results about the reaction of a-silylated carbanions with carbonyl compounds to achieve /3-hydroxyalkyl-silanes. He found that instantaneous elimination affords unsaturated hydrocarbons ( Peterson olefmation )180 Thus, the lithiated trimethyl-benzyl-silane (274) plus benzophenone (135) give via lithium l,l,2,-triphenyl-2-TMS-ethanolate (275) 1,1,2-triphenyl-ethene (276)180 ... 

Hydroxyalkylation of Enolates with Carbonyl Compounds ( Aldol Addition ) Synthesis of /3-Hydroxyketones and /3-Hydroxyesters... 

The first products of the reaction of hydrogen peroxide with carbonyl compounds are a-hydroxyalkyl hydroperoxides (1) and dihydroxy-dialkyl peroxides (2) [Eq. (I)].2,19... 

Further reaction of Aese species with carbonyl compounds and hydrolysis of the resulting alkoxide leads to p-oxidoalkyl selenoxides which have been transformed into allyl alcohols on thermal decomposition (Schemes 51, 52 and 54, entry a see Section 2.6.4.4) or reduced to p-hydroxyalkyl selenides or to alkenes (Scheme 53). P-Oxidoalkyl selenoxides derived from cyclobutanones react in a different way since Aey rearrange to cyclopentanones upon heating (Scheme 54, b. Schemes 120 and 121 and Section 2.6.4.5.3). 

The proton-catalyzed hydroxyalkylation of phenolic substances with carbonyl compounds is one of the reactions in which a weak acid catalyst is required, as strong acids will lead to oligomerization. The possible reaction routes of phenol reacting with the two aldehydes studied are shown in Figure 1. Especially with formaldehyde, mono-substituted products are difficult to obtain, because of the fast consecutive dimerization when larger carbonyl compounds are applied (such as isobutanal), monomer formation might be enhanced because of steric reasons. 

Moreover, the bromo-lithium exchange in irans-configured R, S ) ori/io-bromophenyloxazolinyloxirane 100, followed by reactions with carbonyl compounds, proved to be a useful approach for making oxazolinyl-substituted hydroxyalkyl l,3-dihydrobenzo[c] furans 101 with dr up to 98 2 (Scheme 28) (2007JOC6316). 

The synthesis of simple terminal alkenes has been reported by the reaction of (triphenylstannyl)methyllithium with carbonyl compounds [390]. (Phenylthio)-triphenylstannylmethyllithium and benzaldehyde can be selectively transformed into ( )-yS-(phenylthio)styrene or, alternatively, its Z-isomer via yS-hydroxyalkyl-stannane 241 by means of a tin-Peterson reaction (Scheme 2.148) [391]. LDA is usually used as the base in the tin-Peterson reaction. Butyllithium is not a suitable base for abstraction of the a-proton because lithium-tin exchange may occur [259]. 

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