Dichlorocarbene reaction with alcohols

Although the C=C bond of allyl alcohols is frequently less susceptible to reaction with dihalocarbenes, insertion of the carbene into the C=C bond invariably occurs (Table 7.4) to the exclusion of reaction at the hydroxyl group (see Section 7.5) [98]. A complex mixture of products is obtained from the reaction of dichlorocarbene with allyl alcohol, but the cyclopropane can be obtained in high overall yield (>70%) via... 

The same Japanese chemists5 found that alcohols are converted in high yield into chlorides by reaction with dichlorocarbene generated in this way. Thus 1-adamantyl alcohol is converted into 1-adamantyl chloride in 94% yield, and benzyl alcohol into benzyl chloride in 90% yield. The reaction proceeds with predominant retention of configuration (SNf). 

The 1-allylcycloalkanols (66 n = 0, 1, or 2 R = H) are cyclopropanated to (67 R = H) by dichlorocarbene. Yields are higher using ethyl trichloroacetate and sodium methoxide in hexane than with chloroform-potassium t-butoxide as the carbene source, but the former method gave slightly lower yields on reaction with the trimethyl-silyl derivatives of the alcohols (66 R = SiMe,). This was suggested to beastericeffect and such effects are also seen in the addition of dichlorocarbene to allenes and butatrienes. ... 

Table 3.2. Reaction of alcohols with dichlorocarbene to yield chlorides [6]...

Reaction of dibromocarbene with several adamantyl alcohols has been reported to give the corresponding bromides in low yield [17]. Three such reactions are illustrated in equations 4.9—4.11 [17]. The reaction is analogous to the more thoroughly studied reaction of alcohols with dichlorocarbene (see Sect. 3.3). 

Tabushi reported that dichlorocarbene CC12 reacts with benzyl alcohol to form an O-H insertion product, i.e., benzyl dichloromethyl ether as the primary product, which undergoes a further base-catalyzed elimination reaction to give benzyl chloride as the final product (Scheme 3, Eq. I).14 In contrast to this... 

Predictably, with enynes dihalocarbene addition occurs preferentially with the double bond (equation 17).63 64 The reaction of dichlorocarbene with allenes usually gives rise to spiro-linked dichlorocyclopro-panes (equation 18),65 but rearranged products are obtained in some cases (equation 19).65 66 Somewhat surprisingly, a measure of stereoselectivity has been observed in the formation of dichlorocyclopro-pylcarbinols from secondary allylic alcohols and dichlorocarbene (equation 20).67... 

At this point a benzaldehyde dimethylaeetal is used for the acetah-/ation. The thermodynamically favored six-membered acetal 15 is formed preferentially over the potential competitors five- and sev-cn-membereil acetals5 (See Chapter 7). Transformation of a primary alcohol function into the triflate group of structure 16 must precede the Sn2 reaction in the third step, in which a carbon nucleophile is created with LDA and chloroform. Dcprolonalion of chloroform with LDA is carried out at -110 C to suppress competing formation of dichlorocarbene.6... 

Polymerization. Monomers. The cyclopropane type monomers are prepared either by addition of the dichlorocarbene or by the Simmons-Smith reaction on the corresponding olefins. Most of these compounds have been described. Spiropentane is prepared by the Applequist method (I, 2), by the reaction of zinc with C(CH2Br)4 in alcohol in the presence of ethylenediaminetetraacetic acid (EDTA). This hydrocarbon is purified until a single NMR signal is obtained at t = 9.28. 

The hydroxy group (or the corresponding oxy anion) is the site from which the reactions of dichlorocarbene with saturated alcohols are initiated. Further transformations of intermediates thus formed afford alkyl chlorides, ortho esters, alkenes and other products. These processes are described in detail in Houben-Weyl, Vol. E19b, pp 1575-1578. 

In the case of unsaturated alcohols, the double bond may effectively compete with the hydroxy group for the dichlorocarbene, yet the nature of the final product depends on the structure of the unsaturated alcohol and on the reaction conditions. From the preparative point of view, the chloroform/base/phase-transfer catalyst method gives the best results for the cyclopropanation of unsaturated alcohols (Houben-Weyl, Vol. E19b, p 1542). 

The reaction of allyl alcohol with dichlorocarbene, generated from bromodichloro-methyl(phenyl)mercury/heat or chloroform/base/phase-transfer catalyst, does not afford the corresponding cyclopropane derivative. In the first case, allyl chloride, allyl formate and chloroform were formed and in the second case, tris(allyloxy)ethane (20%), l,l-dichloro-2-... 

Acyclic and cyclic allylic alcohols arc attacked by phase-transfer-generated dichlorocarbene with surprisingly high diastereofacial selectivity24,25. The formation of the major diastereo-mers is consistent with carbene delivery from the side on which the most stable conformer bears the hydroxy group. The unselective reaction of 3-methyl-3-buten-2-ol might be due to an unfavorable allylic 1,3-strain 26 in this conformer. 

Reaction of e J<9-5-hydroxymethyl-2-norbornene with dichlorocarbene generated under phase transfer conditions leads to 3-chloro-5-oxatricyclo-[5.2.1.0 ]-dec-2-ene as the major product (see Eq. 2.21). Formation of this product probably involves initial addition of dichlorocarbene to the carbon-carbon double bond to yield a 1,1-dichlorocyclopropane which ionizes and ring-opens to form a chloro-substituted allylic carbonium ion. This cation is then trapped by the intramolecular nucleophilic alcohol [40]. 

The formation of 1,1-dichlorocyclopropanes from allylic alcohols is of particular synthetic value because the initial adducts can undergo rearrangement under acidic conditions to give good yields of cyclopentenones (see Eq. 2.37) [55]. This result is of mechanistic interest as well since alcohols react with dichlorocarbene to yield the corresponding chloride and carbon monoxide. This reaction is discussed in Chapter 3. In the case of allylic alcohols, dichlorocarbene prefers to react at the carbon-carbon double bond rather than at the hydroxyl function. 

The reactions of dichlorocarbene with a variety of olefinic and acetylenic substrates have been discussed in Chap. 2. We wish now to turn our attention to the reactions of this species with a number of other substrates which either are non-olefmic or contain double bonds which do not constitute the major reactive function. The substrates considered here are alcohols, imines, amines, amides, thioethers, and hydrocarbons. With the exception of the latter, all of these species appear to react by initial coordination of the electrophilic carbene with a Lewis basic site. Subsequent reactions attributable to differences in the basic function or involvement with other reactive sites lead to differences in the chemistry of each substrate, and each is therefore considered separately. 

Menthyl alcohol reacts with dichlorocarbene under phase transfer conditions to yield predominantly /-menthyl chloride, a fact which suggests that an SNi pathway is important although not unique. A significant amount of leakage into the sequential or carbonium ion pathway probably accounts for the production of almost equal amounts of exo and e small amounts of formate esters are isolated in these reactions, suggesting that hydrolysis of II occurs but is not a major process. Several examples are recorded in Table 3.2. 

The reaction of an allylic alcohol with dichlorocarbene is noted above and in Sect. 

Arasaki, H., Iwata, M., Makida, M., and Masaki, Y. (2004) Synthesis of (R)-(+)-tanikolide through stereospedfic C-H insertion reaction of dichlorocarbene with optically active secondary alcohol derivatives. Chem. Pharm. Bull., 52, 848-852. 

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