Ketones, tribromo

Although the trihalolithiomethanes seem to be predestined to deliver the corresponding dihalocarbenes by spontaneous a-elimination, they have been shown to be stable at temperatures below —100 °C so that they could be characterized by NMR spectroscopy . Furthermore, their nucleophilic reactivity has been demonstrated by the addition to ketones. Herein, the in situ generation of trichloro- and tribromo-lithio-methane 128 and 129 provides a convenient protocol (equation 65) . ... 

Ring-C ketones do not interfere with bromination at C-21. However, if a 3-ketone is also present during the reaction, the A-ring can be brominated simultaneously. This can be followed by dehydrobromination of the A-ring without removal of the 21-bromide. Thus, bromination of a 5a- or 5j -pregnane-17a-ol-3,20-dione gives a 2,4,21-tribromo compound which can be dehydrobrominated to a 21-bromo-17a-hydroxypregna-l,4-dien-3-one.173,199... 

Phenols are transformed into aryl chlorides by PhPCl4779. Aromatic and aliphatic aldehydes give, in high yields, gem dibromides with combination of triphenylphosphite and bromine780. Brominative deoxygenation of ketones is achieved by 2,2,2-tribromo-l,2,3-benzodioxaphosphone781. Allylic alcohols are transformed into allylic iodides by reaction with P2I4782. 

Oxabicyclo[3.2.1]oct-6-en-3-ones (75) are also readily transformed to tropones (97) or y-tropolones (98) in a few steps. The tricyclic adduct (75 R = (CH2)9) can be readily converted to troponophane (101). Successful use of tetrabromoacetone and tribromo derivatives of methyl alkyl ketones in these reactions opens a new route to various naturally occurring troponoid compounds, viz. nezukone (102), a-thujaplicin (103) and hinokitiol 0-thujaplicin) (104), = respectively (Scheme 24). 

Trichloroacetamido)phenyl ketone.s 18 or their tribromo analogs are, in most cases, readily converted to the corresponding 4-substituted quinazolin-2(l//)-ones 19 by reaction with ammonia via loss of the trihalomethyl function. Under similar conditions, the 2-trifluoroac-etamide derivative reacts to yield 2-(trifluoromethyl)quinazoline. The mechani.sm of this... 

Finally the tribromo ketone adds water and CBtj is a just good enough leaving group to leave the tetrahedral intermediate with C-C bond cleavage (cf. the bromination reaction, p. 537). The anion is protonated by water as it goes. 

Furthermore, in a series of papers Fuson and co-workers have shown that base-cleavage of the trihalo ketone is strongly retarded by adjacent bulky groups.11 13 For example, cc,cc,cc-tribromo-2,4,6-trichloroacetophenone is unaffected by extended treatment with cold solutions of hydroxide.11 Interestingly, 1,1,1-trichloropropanone is found in chlorine-treated drinking water and is presumed to be a precursor of chloroform that is ubiquitous in such water.14... 

After the necessary stereochemical transformation is performed, the newly formed double bond is reduced and the ketone converted to a tribromo derivative. The bromine at Cs will be displaced by the adjacent hydroxyl group in a nucleophilic reaction, forming a stable five-membered ring. The double bond between C and Ca was formed in the same way as before. A possible mechanism for this transformation is as follows ... 

Monochloro, monofluoro, aliphatic alcohols, ketones Dichlori, difluoro, monobromo derivatives Trichloro, anhydrides Monoiodo, dibromo, nitro derivatives Diiodo, tribromo, polychlorinated aromatics... 

Remarkably, ketone halogenation also occurs in biological systems, particularly in marine alga, where dibromoacetaldehyde, bromoacetone, 1,1,1 -tribromo-acetone, and other related compounds have been found. 

Propose a series of mechanistic steps to convert the tribromo-ketone into the carboxylate. What is the leaving group Why do you think this species is capable of acting as a leaving group in this process ... 

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