Homopropargylic acetylenes

Scheme 10-112 Intramolecular hydrosilylation of homopropargylic acetylenes proceeds with excellent stereo- and regiocontrol. Reagents and conditions i) [H2PtCl6 6H2O] (0.1 mol%), CH2CI2, rt ii) 30% H2O2, KF, KHCO3, MeOH, THF, 30 "C iii) Br2,0 °C then KHF2, MeOH, rt.

It is also difficult to determine exactly the relative stabilities of vinyl cations and the analogous saturated carbonium ions. The relative rates of solvolysis of vinyl substrates and their analogous saturated derivatives have been estimated to be 10 to 10 (131, 134, 140, 154) in favor of the saturated substrates. These rate differences, however, do not accurately reflect the inherent differences in stability between vinyl cations and the analogous carbonium ions, for they include effects that result from the differences in ground states between reactants, as well as possible differences between the intermediate ions resulting from differences in solvation, counter-ion effects, etc. The same difficulties apply in the attempt to estimate relative ion stabilities from relative rates of electrophilic additions to acetylenes and olefins, (218), or from relative rates of homopropargylic and homoallylic solvolysis. 

Reaction of the transient zinc intermediates with various electrophiles yielded the acetylenic substitution products and only minor amounts of allenes (Table 9.49). Reactions with aldehydes were non-selective, affording mixtures of stereo- and regioisomeric adducts. However, prior addition of ZnCl2 resulted in the formation of the homopropargylic alcohol adducts with high preference for the anti adduct, as would be expected for an allenylzinc chloride intermediate (Table 9.50). 

The effect of the BF3 activation on the regioselectivity of the ring opening of vinylic and acetylenic oxiranes is dramatic, as in these conditions the reaction occurs exclusively on the allylic " or the propargylic " position, and still with inversion (Scheme 40). This excellent regioselectivity allows the direct stereospecific preparation of homoallylic and homopropargylic alcohols in excellent yields. In the case of acetylenic oxiranes, a remarkable difference in the reactivity of cis and trans oxiranes has been evidenced, the former being more reactive. 

Excellent yields can be obtained when the mixture of RC=CLi and the epoxide in ammonia is allowed to stand for 12 to 24 hours [2]. With sodium acetylides, there is some risk of subsequent attack of the acetylenic alcoholate on the epoxide, especially when the latter compound is used in excess. The reaction of acetylenic magnesium halides, RCsCMgX, with epoxides also leads to homopropargylic alcohols, but this is generally not recommended as a satisfactory method, as impure products are often obtained [62], Coordination of the epoxide-oxygen atom with the Lewis acid may give rise to a Sjql-like attack of RCaC on... 

In a subsequent study, Miginiac and coworkers examined additions of allenylzinc reagents to an ZV-TMS imine derived from the mono diethyl acetal of acetylene dicarboxaldehyde10. These additions afforded the homopropargylic adducts as the free primary amines (equation 13). 

Sequential treatment of an ethynylalkanol acetate with butyllithium and a trialkyl-borane produces an allenic borane (23), which when protonated with acetic acid forms an allene, while upon treatment with water affords an acetylene derivative, presumably via a cyclic process (Eq. 51) A novel synthesis of homopropargylic... 

Imines react with alkynes to give pyrroles (equation 29). " A related transformation of azides has been reported by the group of Toste to afford pyrroles by an acetylenic Schmidt reaction (equation 30). " In an intermolecular-related addition, gold triazolates are obtained. The intramolecnlar hydroamination of trichloroacetimidates derived from propar-gyl and homopropargyl alcohols also proceeds with cationic An(I) as catalysts. ... 

Stable gem-difluoroallenylindiurri(l) is prepared from bromodifluoromethyl silyl acetylene, which couples with aldehydes to give homopropargylic gem-difluoro alcohols with aqueous formaldehyde allenyl alcohols are obtained (Scheme 8.3) [17]. 

Vinylic epoxides such as 2.28 can be reduced by attack on the epoxide carbon atoms according to the usual rules, or they can undergo conjugate reduction, as shown in Figure 2.16 [LKl]. LAH attacks the epoxide at the least substituted carbon, and DIBAH in THF mainly attacks the epoxide at the most substituted one, whereas DIBAH in hexane gives only the conjugate reduction. Acetylenic epoxides are reduced by LAH into homopropargylic alcohols [HDl]. 

Cl 1-25 of the milbemycins. The intramolecular spiroketalization theme was slightly altered to feature an endocyclic enol ether [86] by condensation of a lithio-2-benzenesulfonyl-tetrahydropyran with a suitable epoxide. An alternative but not enantiospecific approach from lactone B 3 comes from a double Baeyer-Villiger oxidation of bicyclo[2.2.1]heptane-2,5-dione to control [107] the relative stereochemistry in the B ring. The acetylenic partner was in turn derived from two different routes, the more selective being an anti hydroxyl group directed alkylation of a homopropargylic alcohol. 

Monosubstituted pyrroles were formed in excellent yields by dehydrative cyclization of acetylenic amino alcohols in the presence of Au[P(t-Bu)2(o-biphenyl)]Cl and AgOTf (Scheme 4-54). The transformation proceeds not only with tosylamides, but also with basic amino groups, even though longer reaction times were required. Homopropargyl azides are also transformed to substituted pyrroles in the presence of cationic gold(I) catalysts. ... 

Toste has reported a gold(I)-catalyzed protocol for the intramolecular addition of an alkyl azide to an alkyne with loss of dinitrogen (acetylenic Schmidt reaction) to form pyrrole derivatives [19]. For example, treatment of homopropargyl azide 16 with a catalytic 1 2 mixture of (dppm)Au2Cl2 (dppm = l,2-bis(diphenylphosphino)meth-ane) and AgSbFfi in methylene chloride at 35 °C led to isolation of2,5-dibutylpyrrole in 82% yield (Eq. (11.13)). The method was also effective for the cyclization of a-unsubstituted homopropargyl azides and tolerated both alkyl and aryl substitution of the alkyne. 

In a protocol, similar to synthesis of homopropargylic alcohol, allenylborane derived from 3-(tert-butyldimethylsilyl)-l-(trimethylsilyl)-l-propyne affords, on condensation with conjugated acetylenic aldehydes (R = -BuC=C and Ph-C=C), the diynic alcohols with high diastereoselectivities. The SR/RS RR/SS ratio is >98 2 (Scheme 6.19) [1] with both aldehydes. 

A new route to homopropargylic alcohols from trimethylsilylallenes and carbonyl compounds is shown in Scheme 23 the corresponding ethers are obtained from the silylallenes and acetals. Dilithio-l-alkynes have been found to react with epoxides (Scheme 24) to product 5,e-acetylenic alcohols. ... 

Trimethylsilylallenes behave as propargylic anion equivalents during the titanium tetrachloride catalysed addition to carbonyl compounds, leading to homopropargylic carbinols. This new approach should prove useful in the synthesis of branched acetylenes which are not accessible via alkylation of acetylide anions with alkyl halides and epoxides (Scheme 23). ... 

Two molar equivalents of homopropargylating agents, such as (118), couple in excellent yield with the cuprates (119) derived from terminal acetylenes, provided that hexamethylphosphoramide and trimethyl phosphite are present in the reaction medium. The coupled products (120) serve as useful precursors to insect pheromones. ... 

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