Peterson Olefination Research Articles

An improved synthesis of α-phosphonoenamines based on a modified Peterson olefination

An efficient, stereoselective method for the synthesis of α-phosphonoenamines based on a modified Peterson olefination is described. The carbanion derived from isolatable intermediate 2 reacts with aromatic or aliphatic aldehydes selectively eliminating in Peterson fashion to deliver functionally rich α-phosphonoenamines 3. The synthetic utility of these enamines is demonstrated by their hydrolysis yielding the homologous carboxylic acids in good yield.

Total Synthesis of (±)-Phomactin B2 via an Intramolecular Cyclohexadienone Annulation of a Chromium Carbene Complex

A total synthesis of (±)-phomactin B2 is described which has as its key step the intramolecular cyclohexadienone annulation of a Fischer carbene complex. The requisite carbene complex was prepared from geraniol in 11 steps and 12 % overall yield. The key cyclohexadienone annulation produced both rings of the [9.3.1] pentadecane ring system of phomactin B2 in a single step in 60% yield and as a 4:1 mixture of diastereomers. The major diastereomer was taken on to the natural product in a series of steps that begins with a Peterson olefination. Initially, the Peterson olefination failed but x-ray analysis of two intermediates in the diastereomeric series revealed that approach to the hindered carbonyl was blocked by a TIPS protecting group. Replacement of the TIPS group with a MOM group led to a facile Peterson olefination. Another notable steps in the synthesis included a stereoselective methylation of a cyclohexenone and hydroxyl directed epoxidation of an alkene.

Peterson olefination from α-silyl aldehydes

A procedure for the stereoselective synthesis of substituted alkenes from alpha-silyl aldehydes, via the Peterson reaction, is described. The protocol for the preparation of alpha-silyl aldehydes is also included. Organometallic addition to the alpha-silyl aldehyde gives erythro-beta-hydroxysilanes in high yields (85-90%), which undergo elimination on treatment with potassium hydride (KH) or boron trifluoride to afford respectively Z- o E-alkenes (87-90%). The method described has been carried out using alpha-silyl aldehydes bearing the tert-butyldiphenylsilyl group. This bulky group increases the stability of the silyl aldehyde, enhances the stereoselectivity of the formation of the beta-hydroxysilanes and favors the stereocontrol of the elimination step, thus providing high yields of stereo-defined alkenes. Here we describe a two-step protocol for the synthesis of Z-1-phenyl-1-hexene from 2-tert-butyldiphenylsilyl-2-phenylethanal and n-butyllithium, followed by elimination of the resulting (1S*,2R*)-1-tert-butyldiphenylsilyl-1-phenylhexan-2-ol with KH. The total time for the synthesis, purification and isolation of the alkene is 2 days.

Diastereoselective Synthesis of 2-Amino-4-phosphonobutanoic Acids by Electrophilic Substitution and Tin−Peterson Olefination of Bis-lactim Ethers Derived fromcyclo-[l-AP4-d-Val

Electrophilic substitutions on lithiated Schöllkopf's bis-lactim ethers derived from cyclo-[L-AP4-D-Val] take place regio- and stereoselectively at the alpha-position of the phosphonate ester. Subsequent olefination of alpha-silyl-, alpha-phosphoryl-, and alpha-stannyl-stabilized phosphonate carbanions give rise exclusively to vinylphosphonates. Both processes allow a direct and stereoselective access to a variety of 4-substituted and 3,4-disubstituted 2-amino-4-phosphonobutanoic acids (AP4 derivatives) in enantiomerically pure form that may be useful tools for characterizing the molecular pharmacology of metabotropic glutamate receptors (mGluRs) of group III. The relative stereochemistry was assigned from X-ray diffraction analyses or NMR studies of 1,2-oxaphosphorinane and other cyclic derivatives. In accordance to density functional theory (DFT) calculations, the syn-selectivity in the electrophilic substitutions may originate from the intervention of seven- and eight-membered chelate structures in which the bis-lactim ether moiety shields one of the faces of the phosphonate carbanion. DFT calculations for the tin-Peterson olefination of alpha-stannyl stabilized phosphonate carbanions indicate that rate and selectivity are determined in the initial carbon-carbon bond formation step where the unlike transition structures leading to (Z)-vinylphosphonates are favored both in the gas phase and in THF solution.

Facile Entry to Substituted Decahydroquinoline Alkaloids. Total Synthesis of Lepadins A−E and H

Condensation of a L-alanine derived delta-bromo-beta-silyloxy-propylamine with 1,3-cyclohexadione followed by alkylative cyclization produces a bicyclic enone. Diastereoselective Pt/C-catalyzed hydrogenation of this enone in HOAc provides a 5-oxo-cis-fused decahydroquinoline. Wittig olefination of this decahydroquinoline and subsequent epimerization of the resulting 5-formyl intermediate gives rise to a 5-beta-formyl decahydroquinoline exclusively. In a parallel procedure, Peterson reaction of this decahydroquinoline and subsequent hydrogenation of the generated 5-exo-olefin provides a decahydroquinoline with a 5-alpha-substituent predominantly. For these two diastereoselective processes, using the intermediates without N-protection as the substrates is essential because the corresponding N-Boc intermediates give poor diastereoselectivity. The intermediate with beta-form side chain is further converted into lepadins A-C via carbon chain elongation, while the intermediate with alpha-form side chain is transformed into lepadins D, E, and H and corresponding 5'-epimers via connection with two sulfones generated from two Sharpless epoxidation products. By comparison of the rotations and NMR data, the stereochemistry of lepadins D, E, and H is assigned as 2S,3R,4aS,5S,8aR,5'R.

Radion Reactions to Form Vinylphosphonothioates.

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A New Short and Efficient Route to 3-Deoxy-d-manno-oct-2-ulosonic Acid (KDO) and 3-Deoxy-d-arabino-hept-2-ulosonic Acid (DAH)

An efficient synthesis of lactones 5 and 6, known intermediates towards KDO and DAH, respectively, has been achieved by a short and highly efficient route. Homologation of protected D-mannose and D-arabinose was performed by a Peterson reaction with 2-lithio-2-trimethylsilyldithiane or the corresponding bis(methylsulfanyl) derivative, followed by the cyclization of the resulting ketene dithioacetal under very smooth conditions. An oxidative treatment with iodine gave the lactones 5 and 6 in a three-step sequence with high yields. Interestingly, this approach can be considered as a general method for the synthesis of various 2-deoxysugar lactones.

Radion Reactions To Form Vinylphosphonothioates

Radical addition of diethyl thiophosphite to terminal alkenes followed by consecutive α-silylation and Peterson reactions, efficiently forms vinylphosphonothioates, in one-pot radion reactions.

Total Synthesis of (+)‐Dactylolide Through an Efficient Sequential Peterson Olefination and Prins Cyclization Reaction.

Total Synthesis of (+)‐Dactylolide Through an Efficient Sequential Peterson Olefination and Prins Cyclization Reaction.

Synthesis of tricyclic vinylcyclobutanes and their application in photoinduced electron transfer chemistry

The synthesis of new tricyclic vinylcyclobutanes is reported. These compounds were prepared in good yields from the ketones via a two step Peterson olefination. Under conditions of photoinduced electron transfer some tricyclic vinylcyclobutanes show interesting skeleton rearrangements.

One or More C:C Bond(s) by Elimination of S, Se, Te, N, P, As, Sb, Bi, Si, Ge, B, or Metal Functions

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Total Synthesis of (+)‐Dactylolide through an Efficient Sequential Peterson Olefination and Prins Cyclization Reaction

Total Synthesis of (+)‐Dactylolide through an Efficient Sequential Peterson Olefination and Prins Cyclization Reaction

Total Synthesis of (+)‐Dactylolide through an Efficient Sequential Peterson Olefination and Prins Cyclization Reaction

Total Synthesis of (+)‐Dactylolide through an Efficient Sequential Peterson Olefination and Prins Cyclization Reaction

Synthesis of new nucleoside analogues comprising a methylenecyclobutane unit

Synthesis of eight nucleoside analogues 3– 10 with a methylene cyclobutane unit is described. Wittig or Peterson reactions with protected 2-hydroxycyclobutanones 12 and 13 gave E- and Z-derivatives, respectively. After functional modifications the heterocyclic moieties were introduced via a Mitsunobu reaction either on the lateral chain or on the cycle. When adenine was used in this reaction only the N-9 substitution products were obtained. Removal of the protecting groups provided the target products.

Evaluation of C‐Trialkylsilyl Enol and Thioenol Ethers as Intermediates in the Synthesis of Acylsilanes.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Highly (Z)‐Selective Synthesis of β‐Monosubstituted α,β‐Unsaturated Cyanides Using the Peterson Reaction.

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Stereochemistry of the Reaction of Si‐Phenyl Silenes with Butadienes: Elaboration of the Silacycloadducts to Provide a Novel Route to Substituted Lactones.

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Efficient and Selective Synthesis of 6,7‐Dehydrostipiamide via Zr‐Catalyzed Asymmetric Carboalumination and Pd‐Catalyzed Cross‐Coupling of Organozincs

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Evaluation of C-trialkylsilyl enol and thioenol ethers as intermediates in the synthesis of acylsilanes

C-silyl enol ethers or thioenol ethers have been prepared by a Peterson reaction, as intermediates for acylsilane synthesis. Bis(trialkylsilyl)(methoxy)- or -(methylsulfanyl)methanes bearing identical or different trialkylsilyl groups were used as starting materials in order to assess the selectivity of the Peterson elimination step. A good selectivity was observed only with ethers bearing the TMS and TBDMS groups. However, there is no practical interest to use such reagents owing to the difficulty to obtain them in correct yields. Bis(trimethylsilyl)(methylsulfanyl)methane proved to be a good reagent for the preparation of C-silyl thioenol ethers, which are hydrolyzed under classical acid conditions to give acylsilanes in fair overall yields. This convenient procedure was extended to the synthesis of bis(acylsilanes).

Highly (Z)-Selective Synthesis of β-Monosubstituted α,β-Unsaturated Cyanides Using the Peterson Reaction

[reaction: see text] The Peterson reaction between (t-BuO)Ph(2)SiCH(2)CN and various aldehydes furnishes the corresponding beta-monosubstituted alpha,beta-unsaturated cyanides with high Z selectivity (Z:E = 92:8 to >98:2).