Functionalized cuprates

Sdieine 6.2. Diactereocelective addition of a functionalized cuprate to cyclopentenone 14 in the cynthecic of proctaglandin E (PCE ) (TBS = t-butyldimethylcilyl,... 

The coupling process, which has been extended successfully to functionalized cuprates, can also be performed with alkylzinc chlorides in the presence of catalytic amounts of cuprous salts (e.g. CuCN-2LiCl, CuBr-Me2S and LiCuBr2), providing products with excellent alkyne/allene selectivity (143 144= 91 9 to 100 0) (Scheme... 

The highly functional cuprate reagent (12) reacts with acid chlorides to give ketones which are capable of further modification by rearrangement. "... 

Good stereoselectivity is observed in the addition of lithium dialkylcuprates to 4-, 5-, and 6-alkyl-substituted cycloheptenones. Stork has used the stereoselectivity of addition of functionalized cuprates to the conformationally rigid enone-lactone (104) to produce (on further modification) the trans-fused hydrindone (105) [equation (65)]. ... 

A further improvement in the cuprate-based methodology for producing PGs utilizes a one-pot procedure (203). The CO-chain precursor (67) was first functionalized with zirconocene chloride hydride ia THF. The vinyl zirconium iatermediate was transmetalated direcdy by treatment with two equivalents of / -butyUithium or methyUithium at —30 to —70° C. Sequential addition of copper cyanide and methyUithium eUcited the /V situ generation of the higher order cyanocuprate which was then reacted with the protected enone to give the PG. 

A drawback of tlie Z enoates is usually lower reactivity, rehected in prolonged reaction times and bigliet reaction temperatures. Tliis may be overcome by switdi-ing to more reactive enone systems. Tlius, addition of tlie functionalized cyano-G dnian cuprate s7stem 67 to Z enone 66 proceeded smootlily at low temperatures, witli excellent acydic steteocontrol at tlie /J-steteocenter [26, 27]. Stereocontrol upon... 

It has been proposed dial a directed cuprate addilioti widi a carbamate or a carbonate serving as a reagenl-directing functional group may account for die stereo-clieniical outcome of diese reactions fsee models 115 and 116 in Sclieme 6.25) [39,... 

The conversion of a thiolactone to a cyclic ether can also be used as a key step in the synthesis of functionalized, stereochemically complex oxacycles (see 64—>66, Scheme 13). Nucleophilic addition of the indicated higher order cuprate reagent to the C-S double bond in thiolactone 64 furnishes a tetrahedral thiolate ion which undergoes smooth conversion to didehydrooxepane 65 upon treatment with 1,4-diiodobutane and the non-nucleophilic base 1,2,2,6,6-pentamethylpiperidine (pempidine).27 Regio- and diastereoselective hydroboration of 65 then gives alcohol 66 in 89 % yield after oxidative workup. Versatile vinylstannanes can also be accessed from thiolactones.28 For example, treatment of bis(thiolactone) 67 with... 

Most gratifyingly, these conditions are also applicable to functionalized magnesium reagents [33], as demonstrated by the formation of a-hydroxyallenes 31-34 from ds- or trans-27 and the corresponding magnesium cuprates bearing substituted aryl groups (Scheme 2.11) [31]. 

Scheme 2.11 a-Hydroxyallenes obtained by SN2 substitution of propargyl oxirane 27 with functionalized magnesium cuprates. 

The related zinc cuprates formed from diorganozinc reagents and copper(I) cyanide also undergo smooth SN2 substitution reactions with propargyl oxiranes in the presence of phosphines or phosphites (Scheme 2.12). These transformations can also be performed with catalytic amounts of the copper salt since no direct reaction between the organozinc reagent and the substrate interferes [31, 34], and therefore should also be applicable to functionalized organozinc compounds. 

Scheme 2.28 Functionalized allenes obtained by 1,6-cuprate addition to acceptor-substituted enynes and regioselective enolate trapping with methyl triflate (77), aldehydes (78, 79), ketones (80) and silyl halides (81).

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