Propargylic mesylate

Chiral allenylstannanes can be prepared by Sjv2 displacement of propargylic halides sulfinates or sulfonates with tin cuprates (Table 14)78. The nonracemic propargylic mesylate (74) afforded a nonracemic allene, [a]D —570, whose configuration was assigned by application of Brewster s rules (equation 38)78. Displacements on the steroidal mesylates 75 and 76 afforded the allenic products with complete inversion of configuration (Scheme 32)78. 

Various nonracemic allenylstannanes have been prepared from nonracemic propargylic mesylates and (Bu3Sn)2CuLi. The stereochemistry of the displacement was shown to be anti by correlation with an allenic stannane prepared through Claisen orthoester rearrangement of a propargylic alcohol of known configuration (Scheme 33)80. 

Due to its reliability, the SN2 substitution is often used in applications which require the highly enantioselective formation of the allene for example, Brummond et al. [19g] prepared the yneallene 19 (a starting material for intramolecular allenic Pauson-Khand cycloadditions) through the anti-selective SN2 substitution of the chiral propargylic mesylate 18 with a suitable magnesium cuprate (Scheme 2.6). 

Scheme 2.6 Anti-stereoselective SN2 substitution of propargylic mesylate 18.

Scheme 2.43 Formation of allenes from propargyl mesylates and lithium triorganozincates.

Scheme 4.32 Palladium(0)-catalyzed reduction of propargyl mesylates forming allenes.

Int. Ed. 2000, 39, 4355—4356 they also reported the organocopper-mediated 1,3-sub-stitution of a chiral propargyl mesylate, prepared by Baker s yeast reduction, to afford an optically active allene with 89% ... 

The route has also been applied to TBS-substituted propargylic mesylates (Eq. 9.39) [45]. Interestingly, the isomeric propargylic silanes are not formed despite the more attractive steric environment for a direct SN2 displacement at the primary center. 

Trialkyl- or triarylallenyltin compounds can also be prepared by Sn2 displacement of propargylic mesylates with various stannylcopper reagents in THF (Eq. 9.82) [71]. This reaction is postulated to proceed by an anti Sn2 pathway based on the stereochemical relationship between the enantioenriched mesylate and the allenic product (Eq. 9.83). The allene obtained from the reaction of the mesylate of (R)-3-phenyl-l-propyn-3-ol with Ph3SnCu was assigned the (P) configuration from a consideration of the observed optical rotation and an application of Brewster s rules [71]. 

Whereas tin cuprate displacements of terminal propargylic mesylates lead exclusively to allenic stannanes (Eqs. 9.82 and 9.83), the reaction of an internal propargylic mesylate with Ph3SnCu afforded a mixture of allenic and propargylic isomers (Eq. 9.84) [71]. 

The palladation of propargylic mesylates is known to occur with inversion of configuration [113]. The predominant formation of anti products strongly suggests a cyclic transition state for the addition. It can therefore be surmised that the zincation reaction proceeds with retention of configuration. A possible catalytic cycle is shown in Scheme 9.28 [110]. 

Scheme 9.28 Possible catalytic cycle for the Pd (0)-catalyzed zincation of propargylic mesylates.

Terminal propargylic mesylates are converted to alkylallenylzinc compounds by reaction with lithiotrialkylzincate reagents (Scheme 9.32) [117]. The latter are formed in situ from dialkylzinc and alkyllithium species. Deuterolysis of the allenylzinc intermediates gave rise to deuterated allenes (Eq. 9.138). 

Scheme 9.32 Synthesis of allenylzinc reagents from propargylic mesylates.

Allenyl iodides can be prepared from propargylic mesylates by Sn2 displacement with LiCuI2 (Eq. 9.143) [118]. The reaction proceeds primarily by an anti pathway with slight racemization. Metallation of these iodides with powdered indium in various donating solvents leads to transient allenylindium intermediates which react in situ with aldehydes to afford anti homopropargylic alcohols (Table 9.52). Additions... 

A more satisfactory sequence, which also starts with enantioenriched propargylic mesylates, generates the allenylindium intermediate by oxidative transmetallation of an allenylpalladium precursor with Ini. This catalytic process takes place in the presence of an aldehyde. The reaction employs 5-10 mol% of the palladium catalyst and a stoichiometric quantity of Ini. Based on the stereochemistry of the starting... 

Propargylic mesylates show only modest diastereoselectivity in Pd(0)/lnl-mediat-ed additions to unbranched and conjugated aldehydes [118]. However, the presence of a terminal trimethylsilyl substituent on the alkynyl grouping greatly improves the diastereoselectivity of such additions (Table 9.55) [119]. 

Panacene (61) is a metabolite of the sea hare Aplysia brasiliana and acts as a fish antifeedent [61]. The synthesis of the racemic natural product, published by Feldman et al. [77] in 1982, takes advantage of the anti-selective SN2 -substitution of the propargylic mesylate 67 with LiCuBr2 (Scheme 18.21). In contrast, the later attempted biomimetic synthesis by treatment of the enyne 68 with NBS or 2,4,4,6-tetrabromocyclohexadienone did not proceed stereoselectively and led to a 1 1 mixture of the target molecule 61 together with its allenic epimer [78]. 

The bromoallene (-)-kumausallene (62) was isolated in 1983 from the red alga Laurencia nipponica Yamada [64a], The synthesis of the racemic natural product by Overman and co-workers once again employed the SN2 -substitution of a propargyl mesylate with lithium dibromocuprate (Scheme 18.22) [79]. Thus, starting from the unsymmetrically substituted 2,6-dioxabicyclo[3.3.0]octane derivative 69, the first side chain was introduced by Swern oxidation and subsequent Sakurai reaction with the allylsilane 70. The resulting alcohol 71 was protected and the second side chain was attached via diastereoselective addition of a titanium acetylide. The synthesis was concluded by the introduction of two bromine atoms anti-selective S -substitution of the bulky propargyl mesylate 72 was followed by Appel bromination (tetrabromo-methane-triphenylphosphine) of the alcohol derived from deprotection of the bromoallene 73. 

An alternative preparation of enantioenriched anti-homopropargylic alcohols along similar lines uses EtjZn to effect in situ transmetallation of an allenylpalladium intermediate from a propargyl mesylate and 2.5 mol % of Pd OAc)2 PPh3 in the presence of an aldehyde (Table II). The two methods are comparable. 

Besides alkoxy-, amino-, and amidocarbonylation reactions, a carbonylation process using a thiol as nucleophile, that is, thiocarbonylation, has been extensively studied.It has been shown that the thiocarbonylation takes place with 1-alkynes, " " " propargyl alcohols,allenes, " 1,3-dienes, propargylic mesylates, " and bicyclopropylidene . 

The reaction of 1-alkynes 275 gives thioformylation products 277 (Equation (21)), " while that of propargyl alcohols 278 afforded thiofuranones 280 (Equation (22)). The reaction of allenes 281 gives alkenylthiolate 282 (Equation (23)), while dithiocarbonylation took place to yield 284 in the reaction of propargylic mesylates 283 (Equation (24)). ... 

Propargylic mesylates such as fluorine-substituted derivative 265 react with PhZnCl in the presence of Pd(PPh3)4 (5 mol%) in THF at 0°C within 2 h to provide the anti-Si 2 product in excellent yield and complete transfer of the stereochemistry leading to the allene 266 (Scheme 78). Copper(I) catalyzed allylic substitutions with functionalized diorganozincs proceed with high 8 2 selectivity. Thus, the reaction of the chiral allylic phosphate 267 with 3-carbethoxypropylzinc iodide in the presence of CuCN 2LiCl (2 equivalents) furnishes the awf/-Sjv2 substitution product 268 in 68% yield. By the addition of w-BuLi (1.2 equivalents) and TMSCl (1.5 equivalents), the bicyclic enone 269 is obtained in 75% yield and 93% ee (Scheme 79) . 

A novel approach to allenylzinc reagents, reported by Oku and coworkers, employs propargylic mesylates as starting materials12. Treatment with triorganozincates, prepared in situ by the reaction of dialkylzinc compounds with organolithium reagents, affords transient allenyl dialkylzinc intermediates. These intermediates were found to react with various... 

TABLE 9. Trapping of ethylzinc allenyl reagents prepared from propargylic mesylates... 

In an extension of the methodology reported by Tamaru and coworkers for allylic benzoates16, Marshall and Adams found that propargylic mesylates could be converted to allenylzinc reagents with Pd(0) catalysts and an equivalent of Et2Zn17,18. When this novel palladiozincation reaction was conducted in the presence of aldehydes, anti homopropar-gylic alcohols were produced as the major adducts (Tables 14 and 15). 

FIGURE 2. Proposed catalytic cycle for palladiozincation of propargylic mesylates... 

TABLE 16. Preparation of trifluoromethylallenylzinc reagents from trifluoromethyl-substituted propargylic mesylates... 

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