Amines homopropargylic

In furtherance of these smdies, the reaction scope was broadened by employing homopropargylic amines to give the corresponding aza-cycles (Scheme 26) [39, 40]. Hence, the alkyne aza-Prins cyclization between homopropargyl tosyl amines... 

Scheme 26 Synthesis of 2-aikyl-4-halo-1 -tosyl-1,2,5,6-tetrahydropyridines from A-tosyl homopropargyl amine and aldehydes using FeX3 as promotor...

A plausible mechanism for this new alkyne aza-Prins cyclization is outlined in Scheme 27. Thus, reaction of the homopropargyl tosyl amine with an aldehyde promoted by ferric halide generates the W-sulfonyl iminium ion. This intermediate evolves to the corresponding piperidine, via the vinyl carbocation. Ah initio theoretical calculations support the proposed mechanism. 

Cyclization to six-membered rings (Eq. 15) provided modest diastereoselectivity and required the use of bulkier PhMeSiH2 to prevent olefin hy-drosilylation. Propargyl and homopropargyl amines 94 afforded a variety of heterocycles (Scheme 21), if the catalyst was added slowly over the reaction course to diminish side reactions resulting from metal coordination to the basic amine [56]. The reaction procedure was extended to the diastereoselect-ive bicyclization of dienyne substrate 95, giving 96 as product in a cascade fashion (Eq. 16) [57]. 

A tertiary homopropargylic alcohol could also be prepared by treatment of ethyl acetate with two equivalents of B-allenyl-9-BBN. However, the reaction proceeded slowly and was not general for other esters, which proved to be unreactive, as were tertiary amides and alkyl halides. However, homopropargylic amines could be prepared in high yield and with minimal allenic byproduct through allenylboration of imines with B-allenyl-9-BBN (Eq. 9.24). 

Allenyltrichlorosilanes can also be prepared by Sn2 displacement of propargylic chlorides with a Cu or Ni complex of HSiCl3 [56]. The reaction requires an amine base and a donor solvent such as THF or propionitrile (Table 9.32). Conditions can be adjusted to favor the propargylic or allenic silane, which is not isolated, but treated directly with various aldehydes to afford allenylcarbinols (A) or homopropargylic alcohols (B). These reactions presumably proceed by an SE2 pathway, such that the allenyl products arise from the propargylic silane and vice versa. 

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). 

As a general rule, allylic organozinc reagents do not react with unactivated a, ji-disubstituted alkynes. A few exceptions to this trend have been observed in the case of substrates bearing an appropriately located heteroatom such as the homopropargylic tertiary amine 147. The latter reacted regioselectively with allylzinc bromide but led to a 67/33 mixture of two geometric isomers, apparently derived from syn and anti additions (equation 71)82,105. 

Zn, BrCH2CH2Br, CuBr, LiBr, EtOH (propargylic and homopropargylic alcohol and amine, propargyhc ether, enyne, diyne)... 

The reaction of homopropargylic ketones with primary amines is an excellent method for the synthesis of highly substituted pyrroles. As shown for one example in Scheme 12.16, the yields often are better with the silver catalyst.33... 

Functionalized piperidines 165 and 166 for the synthesis of enantiopure homokainoids have been generated in excellent yields via a Rh-catalyzed cyclohydrocarbonylation reaction on both homoallylic amines 167 and homopropargylic amines 168 <07JOC9418>. 

Furthermore, trifluoroacetic acid anhydride treatment of allylic, propargylic, homopropargylic, and some benzylic tertiary 2,4-dimethoxybenzyl amines 7 leads to highly selective cleavage of their benzylic C —N bonds. The resultant trilluoroacetamides (e,g 8a) can then be readily converted into the corresponding secondary amines. ... 

Interestingly, the presence of a bis-homopropargylic secondary amide does not lead to insertion into the N-H (as happens with a tungsten catalyst [8c]) competing with formation of the dihydropyran as shown in Equation 1.4 [10]. This reaction extends to the insertion into a phenolic OH to form benzofurans (Equation 1.5). In this case, the presence of an amine such as n-butylamine or pyridine appears to be required [11]. It should be noted that insertion into the benzylic OH to form the pyran system does not compete. 

This section covers cyclizations to the pyrrole nucleus catalyzed by other metals (Ti, Mn, Ru, Pd, Pt, Zn, In). Dembinski and co-workers used zinc(II) chloride as ligand-free catalyst for the microwave-assisted cyclization of homopropargyl azides 26 to afford substituted pyrroles 27 (Scheme 8) [62]. A similar methodology for the synthesis of 2,4,5-trisubstituted pyrroles was described by Driver et al. employing substituted 1-azidobuta-l,3-dienes in a cyclization reaction using catalytic amounts of zinc(ll) iodide [63]. A three-component zinc-catalyzed one-pot cyclization of aromatic and aliphatic propargylic acetates, silyl enol ethers, and primary amines to substituted pyrroles has been described by Zhan et al. The reaction sequence includes propargylation of the silyl enol ether, amination, 5-exo-(7ig-cyclization, and isomerization [64]. Hiroya and co-workers have shown... 

In numerous synthetic studies it has been demonstrated that DMP can be used for a selective oxidation of alcohols containing sensitive functional groups, such as unsaturated alcohols [297,1215-1218], carbohydrates and polyhydroxy derivatives [1216, 1219-1221], silyl ethers [1222,1223], amines and amides [1224-1227], various nucleoside derivatives [1228-1231], selenides [1232], tellurides [1233], phosphine oxides [1234], homoallylic and homopropargylic alcohols [1235], fluoroalcohols [1236-1239] and boronate esters [1240]. Several representative examples of these oxidations are shown below in Schemes 3.349-3.354. Specifically, the functionalized allylic alcohols 870, the Baylis-Hillman adducts of aryl aldehydes and alkyl acrylates, are efficiently oxidized with DMP to the corresponding a-methylene-p-keto esters 871 (Scheme 3.349) [1217]. The attempted Swern oxidation of the same adducts 870 resulted in substitution of the allylic hydroxyl group by chloride. 

Amines have also been applied as nucleophiles.f Under the catalysis of the palladium, the o-iodobenzyl homopropargyl ether 52 formed the seven-membered ring vinyl-palladium intermediate 53, which subsequently reacted with 1,2-propadiene in the presence of a secondary amine to eventually afford 54 (Scheme 20). 

Representative procedure for the gold-catalyzed cyclization of aryl homopropargyl amines. Diethyl 6-bromo-1,4-dimethyl-1H-quinoline-2,2-dicarboxylat ... 

Brown and coworkers [11] have demonstrated that B-allenyl-9-BBN reacts vigorously with imines (Eq. 12.5) at room temperature and affords the correspon -ing homopropargylic amines in excellent yields along with a smaU amount o (2-4%) of the allenic amines (Table 12.3) [11]. 

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