Reductions Grignard addition

Grignard and alkyl lithium reagents were found to add to the carbonyl group of a tricyclic vinylogous amide. However, the same compound underwent the usual vinylogous reduction with lithium aluminum hydride (712). Grignard additions to di- and trichloroenamines gave a-chloro- and dichloroketones (713). 

There has been recent interest in naphtho-fused dithiepines as chiral acyl anion equivalents, particularly since the starting dithiol 128 can be obtained in enan-tiomerically pure form (89TL2575). This is transformed using standard methods into the dithiepine 129, but showed only moderate diastereoselectivity in its addition to carbonyl compounds. On the other hand, as we have seen previously for other systems, formation of the 2-acyl compound 130 and reduction or addition of a Grignard reagent gave the products 131 with much better stereoselectivity (91JOC4467). 

The reduction of carbonyl compounds by reaction with hydride reagents (H -) and the Grignard addition by reaction with organomagnesium halides (R - +MgBr) are examples of nucleophilic carbonyl addition reactions. What analogous product do you think might result from reaction of cyanide ion with a ketone ... 

Grignard additions are sensitive to steric effects and with hindered ketones a competing process leading to reduction of the carbonyl group can occur. A cyclic TS is involved. 

The enantioselective synthesis in Scheme 13.22 is based on stereoselective reduction of an a, (3-unsaturated aldehyde generated from (—)-(.V)-limonene (Step A). The reduction was done by Baker s yeast and was completely enantioselective. The diastereoselectivity was not complete, generating an 80 20 mixture, but the diastere-omeric alcohols were purified at this stage. After oxidation to the aldehyde, the remainder of the side chain was introduced by a Grignard addition. The ester function... 

Also other reaction types have been dealt with in CHEC(1984) and CHEC-II(19%) like reduction to alcohols (e.g., sodium borohydride), Wolff Kishner reduction, nucleophilic addition via reaction with Grignard reagents or organo-lithium compounds, and formation of imine type functional groups (e.g., hydrazones). New examples are the reaction of... 

Skraup quinoline synthesis, 443 Smiles rearrangement, phenothiazine, 534 Spiroalkylation, 222, 280 Spirocyclization, conjugate addition, 386 Spiroimidazolone formation, 335 Spiropyrazolopiperidine, 375 Stannylation, alkyne, 15 Stereoselective dehydration, 198 Grignard addition, 198, 199 reduction, 129, 226 hydroxyketone, 400 iminoketone beta, 553 oxazaborohydride, 585 transfer chirality, 321 Stilbene formation, self alkylation, 525 Stobbe condensation, benzophenone, 103... 

Precursor y-halogeno alcohols are frequently prepared by the classic sequence of addition of hydrogen halide to a,/3-unsaturated aldehydes, ketones, acids or esters, followed by Grignard reaction or hydride reduction. Recently a novel and general synthesis of 3-methoxyoxetanes from 3-phenylseleno-2-propenal was reported. This method comprises a sequence of Grignard addition to the aldehyde function, treatment with two equivalents of MCPBA, and then reaction with methanolic sodium hydroxide (equation 78) (80JOC4063). 

Thiophenes have served as important four-carbon templates for molecular elaboration. Both functionalized cyclic and acyclic chains can be generated by carrying out conventional reactions on the thiophene nucleus and then performing a Raney nickel desulfurization at or near the very end of the scheme. Thus, the major constituent (279) of the Panamanian ant, Atta columbica, was made by Friedel-Crafts acylation of the thiophene derivative (277), followed by Grignard addition to the carbonyl group of (278), dehydration, and reductive desulfurization (Scheme 57) (60JOC1754). 

Ozonolysis and subsequent reduction open the way to formyl and hydroxymethyl branched-chain derivatives [18]. High stereoselectivities are generally observed on Grignard addition on conformationally biased ketosugars such as 3 (Scheme 6), equatorial attack being strongly favored, giving the axial alcohol 4 as the major product. 

Reactions of different organometallic species with thiocarbonyi compounds have been extensively investigated and been shown to proceed both in a carbophilic and a thiophilic fashion. However, other reactions can be observed simultaneously such as reduction, double addition, coupling, deprotonation and formation of enesulfides1,226,423. A complex pattern appears in the reactions of thioketones with lithium or Grignard reagents424. The first application of Reformatsky reagents in C—C bond formation by reaction with... 

To achieve synthesis of (-)-arisugacin A [1], (7 J-89 was obtained readily from 2-methyl-l,3-cyclohexanedione 88 in 4 steps with an overall yield of 46%, featuring vinylogous ester formation, Stork-Danheiser double alpha methylation,52,68,69 vinyl Grignard addition followed by acidic work-up,68 and an asymmetric CBS reduction [Scheme 21].70,71... 

Grignard additions, 9, 59, 9, 64 indium-mediated allylation, 9, 687 in nickel complexes, 8, 150 ruthenium carbonyl reactions, 7, 142 ruthenium half-sandwiches, 6, 478 and selenium electrophiles, 9, W11 4( > 2 in vanadocene reactions, 5, 39 Nitrites, with trinuclear Os clusters, 6, 733 Nitroalkenes, Grignard additions, 9, 59-60 Nitroarenes, and Grignard reactivity, 9, 70 Nitrobenzenes, reductive aminocarbonylation, 11, 543... 

Grignard additions, 9, 66 radical addition of zincs, 2, 401 zinc-containing reagent additions, 2, 398 Nitroolefins, enantioselective conjugate additions, 10, 382 (Nitrophenylthio)osmocenes, preparation, 6, 634 (Nitrophenylthio)ruthenocenes, preparation, 6, 634 Nitropyridines, reductive aminocarbonylation, 11, 543 Nitroso aldol reaction... 

Of obviously limited scope and efficiency, the Grignard addition method nevertheless provided a usable method for the formation of some of the required tertiary carbinols. An improved method for their stereoselective reduction was therefore sought. 

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