Β-hydroxyphosphine Oxides Research Articles

Fast and Chemoselective Addition of Highly Polarized Lithium Phosphides Generated in Deep Eutectic Solvents to Aldehydes and Epoxides.

Highly polarized lithium phosphides (LiPR2 ) were synthesized, for the first time, in deep eutectic solvents as sustainable reaction media, at room temperature and in the absence of protecting atmosphere, through direct deprotonation of both aliphatic and aromatic secondary phosphines (HPR2 ) by n-BuLi. The subsequent addition of in-situ generated LiPR2 to aldehydes or epoxides proceeded quickly and chemoselectively, thereby allowing the straightforward access to the corresponding α- or β-hydroxy phosphine oxides, respectively, under air and at room temperature (bench conditions), which are traditionally considered as textbook-prohibited conditions in the field of polar organometallic chemistry of s-block elements.

Efficient Oxidative Resolution of 1-Phenylphosphol-2-Ene and Diels–Alder Synthesis of Enantiopure Bicyclic and Tricyclic P-Stereogenic C-P Heterocycles

1-Phenylphosphol-2-ene 1-oxide is effectively resolved by L-menthyl bromoacetate to afford both SP and RP enantiomers of 1-phenylphosphol-2-ene 1-oxide on a multigram scale. The resolved 1-phenylphosphol-2-ene oxide has been found to undergo face-selective and endo-selective cycloadditions with a series of acyclic and cyclic dienes to produce enantiopure P-stereogenic C-P heterocycles of hexahydrophosphindole and hexahydrobenzophosphindole as well as phospha[5.2.1.02,6]decene and phospha[5.2.2.02,6]undecene structures. Conversions of these cycloadducts to the fully saturated heterocyclic systems as well as to their P (III), P = S, P = Se and P-BH3 derivatives have been demonstrated to occur with retention of configuration and preservation of configurational homogeneity at P. A perplexing case of stereomutation at P during reduction of a tricyclic β-hydroxy phosphine oxide by PhSiH3 at 80 °C has been recorded.

Phosphinoyl radical-initiated vicinal hydroxy-phosphorylation of alkenes

A protocol of Mn(OAc)3–mediated α,β-hydroxy-phosphorylation of alkenes with phosphorus-centered radicals generated from diphenylphosphine oxide is described. A combination of steric and electronic factors played an important role in this reaction. The reactions of styrenes bearing ortho-substituent gave the selective β-hydroxyphosphine oxide products.

Copper-catalyzed direct hydroxyphosphorylation of electron-deficient alkenes with H-phosphine oxides and dioxygen

A copper-catalyzed direct hydroxyphosphorylation of electron-deficient alkenes with H-phosphine oxides and dioxygen is reported. The present reaction, proceeds under mild reaction conditions with good functional group tolerance, affording the facile and efficient synthesis of various β-hydroxyphosphine oxides in a scaled-up manner with moderate to good yields.

ChemInform Abstract: Catalyst‐Free Direct Difunctionalization of Alkenes with H‐Phosphine Oxides and Dioxygen: A Facile and Green Approach to β‐Hydroxyphosphine Oxides.

Abstract A simple and catalyst-free method has been developed for the construction of β-hydroxyphosphine oxides through direct difunctionalization of alkenes with H-phosphine oxides and dioxygen under mild conditions. Preliminary mechanistic studies indicated that the hydroxyl oxygen atom of β-hydroxyphosphine oxide originated from the dioxygen and the present reaction might involve a radical process.

Catalyst-free direct difunctionalization of alkenes with H-phosphine oxides and dioxygen: a facile and green approach to β-hydroxyphosphine oxides

A simple and catalyst-free method has been developed for the construction of β-hydroxyphosphine oxides through direct difunctionalization of alkenes with H-phosphine oxides and dioxygen under mild conditions. Preliminary mechanistic studies indicated that the hydroxyl oxygen atom of β-hydroxyphosphine oxide originated from the dioxygen and the present reaction might involve a radical process.

SYNTHESIS OF AN UNNATURAL ANACARDIC ACID ANALOGUE

ABSTRACT The unnatural E isomer of anacardic acid 7 has been synthesized employing the following key steps: Swern oxidation of a diastereoisomeric mixture of β-hydroxyphosphine oxides 13a/b to the corresponding ketone 14 followed by stereospecific reduction to the pure threo isomer 13b which upon treatment with sodium hydride underwent trans elimination to afford the E ester 15.

1,3-Stereocontrol with phosphine oxides: asymmetric synthesis of all four diastereoisomers of a γ′-benzyloxy β-hydroxy phosphine oxide

This paper describes how optically active phosphine oxides with a γ′ stereogenic centre [for example, (R)-1-diphenylphosphinoylheptan-3-yl benzyl ether] can be lithiated and reacted with aldehydes and esters. The reactions exhibit moderate levels of 1,3 asymmetric induction and models are proposed to explain the stereoselectivity observed in terms of the configurational instability and the known structure of lithiated phosphine oxides. We have developed complementary methods for the asymmetric synthesis of all four diastereomeric β-hydroxy phosphine oxides 4-benzyloxy-2-diphenylphosphinoyl-1-(2-furyl)octan-1-ol and our approach constitutes a formal synthesis of all eight possible stereoisomers. A series of similar β-hydroxy phosphine oxides were eliminated to give optically active homoallylic alcohol derivatives.

Control of remote stereochemistry using phosphine oxides: formal synthesis of any stereoisomer diol (RR, RS, SR or SS ) bearing 1,5-related stereogenic centres across an E double bond

γ-Alkenyl β-hydroxy phosphine oxides have been epoxidised stereoselectively to give γ,δ-epoxy β-hydroxy phosphine oxides with high anti stereoselectivity. The γ-anisyl or γ-furyl ring of γ-aryl β-hydroxy phosphine oxides have been cleaved oxidatively to reveal a carboxylic acid and a ketone respectively. In the latter case, the ketone was reduced highly stereoselectively to give (4R*,5S*,6R*)-8-benzyloxy-6-diphenylphosphinoyloctane-1,4,5-triol as a single diastereoisomer with three controlled stereogenic centres. This method was then applied to the synthesis of three of the diastereoisomers of 8-benzyloxy-6-diphenylphosphinoyldodecane-1,4,5-triol with four controlled stereogenic centres; the middle two stereogenic centres were removed using an E-selective Horner–Wittig elimination to give either diastereoisomer of 8-benzyloxydodec-5-ene-1,4-diol with 1,5-related stereogenic centres across an E alkene.

Asymmetric synthesis with diphenylphosphine oxides: Bicyclic aminals and oxazolidines as chiral auxiliaries

Syntheses of six novel phosphine oxide chiral auxiliaries are described. The auxiliaries are composed of the diphenylphosphinoyl (Ph 2PO) group and either proline-derived bicyclic aminals or norephedrine-derived oxazolidines. One auxiliary is used in the synthesis of an optically active β-hydroxy phosphine oxide.

TiCl 4 Mediated LiBH 4 reduction of β-ketophosphine oxides: a high stereoselective route to the synthesis of anti- β-hydroxyphosphine oxides

The reduction of an α-alkyl-β-ketophosphine oxide with LiBH 4 in presence of a strong chelating agent, such as TiCl 4, gives the corresponding β-hydroxyphosphine oxide in high yields and with high anti-diastereoselectivity independently from the size of both the α- and β-alkyl chains.

Norephedrine-derived oxazolidines as chiral auxiliaries-stereocontrolled routes to R or S β-hydroxy phosphine oxides

Reduction of a β-keto phosphine oxide oxazolidine and reaction of an oxazolidine aldehyde with a lithiated phosphine oxide provide stereoselective routes to S or R β-hydroxy phosphine oxides.

Stereocontrolled route to some optically active β-hydroxy phosphine oxides using the stereoselective addition of metallated phosphine oxides to proline-derived keto aminals

An asymmetric Horner–Wittig addition reaction with a chiral auxiliary attached to the electrophile is described. The key step is the addition of metallated phosphine oxides to Mukaiyama's proline-derived keto aminals (for which improved syntheses are described) and a detailed study of the factors affecting the stereoselectivity of these reactions is presented. In particular, by suitable choice of metallation conditions, complementary stereoselectivities are observed: reactions in THF with no additives are syn selective (Felkin non-chelation control) whereas reactions in toluene with added lithium bromide are anti selective (Cram chelation control).

Trans-Cycloalkenes. Part 12. trans,trans- and cis,trans-Cyclonona-1,5-diene

Possible synthetic routes to trans,trans-cyclonona-1,5-diene from the cis,cis-isomer have been investigated using the β-hydroxyphosphine oxide olefin inversion procedure. A stepwise approach via the epoxy-trans-cyclononene (10) failed. However consecutive double elimination involving the bis-β-hydroxyphosphine oxides (11) and (12) gave cis- and trans-1,2-divinylcyclopentane which are believed to have been obtained by rapid Cope rearrangement of first formed ‘parallel’ and ‘crossed’trans,trans-cyclonona-1,5-diene (1A) and (1B) respectively.

Stereocontrolled synthesis of conjugated polyene isoprenoids using phosphine oxide anion intermediates

The potential for the Horner-Wittig reaction in the stereocontrolled synthesis of conjugated polyene isoprenoids is investigated. It is shown that metallations of the Z- and E-phosphine oxides ( 4 and 5), followed by reaction with Z- and E- citrals lead , in single steps, to the corresponding isomeric pentaenes ( 6) showing complete preservaation of the Z- and E-geometries in the starting materials. Although the single step reactions leading to 6 proceed in low overall yields (10-20%), the olefinations occur with >98% E-stereoselectivity. Isolation of the intermediate β-hydroxyphosphine oxides (e.g. 14), followed by subsequent treatment with sodium hydride in dimethylformamide, demonstrate that these features of the reaction are associated largely with the remarkably slow rates of elimination from the eythro-intermediates in comparison with the threo-intermediates. Condensation between 4 and the ester-aldehyde ( 20) leads to the Z- 6 ester 21 (34%). After conversion of 21 into the tetraenal ( 25), reaction with the phosphine oxide ( 26), followed by separation of the erythro-β-hydroxy-phosphine oxide intermediate 27 and treatment with NaH in DMF, leads to the di-Z-octaene ( 28). The octaene 28 shows closely similar spectral data to those found in natural di-Z-phytofluene ( 2) isolated from fruit of the Tangerine tomato, Lycopersicon esculentum var. In a similar manner, reaction between the Z-phosphine oxide ( 4) and the dialdehyde ( 29) produces the di-Z-nonaene ( 33) which has the same chromophore as that found in di-XXX-carotene ( 3) from Tangerine tomato fruits.

Trans-cycloalkenes. Part 9. Optically active trans-cyclo-octenes via resolution of β-hydroxyphosphine oxides. Proof of configuration of bicyclic trans-cyclo-octenes constrained in chair and twist conformations

β-Hydroxyphosphine oxide precursors to trans-cyclo-octenes have been resolved by crystallisation of their menthoxyacetates. Subsequent fragmentation using sodium hydride gives the respective optically active trans-cyclo-octenes. In this way (S)-(+)- and (R)-(–)-trans-cyclo-octene, (S)-(+)-cis,trans-cyclo-octa-1,5-diene, and 4,5-epoxy-trans-octene [(+)-(12)] have been obtained in high optical purity. The epoxy-olefin (+)-(12) can be converted via addition of butadiene, and epoxide opening with lithium diphenylphosphide, into the optically active hydroxyphosphine oxides (+)-(14) and (+)-(15) which are respectively precursors of the optically active bicyclic twist and chair trans-cyclo-octenes (+)-(3) and (–)-(4). Addition of butadiene to (+)-(3) gave (+)-(17) while addition to(–)-(4) gave the meso-compound (18). In this way the twist and chair olefins were identified. Absolute configurations to all the optically active compounds have been assigned by correlation with (S)-(+)trans-cyclo-octene.

Trans- cycloalkenes. Part 8. Bicyclic trans-cyclo-octenes constrained in chair and twist conformations

Bicyctic trans-cyclo-octenes locked in twist (1) and chair (2) forms and their unsaturated analogues (18) and (19) have been synthesised. Key steps are: the Diels–Alder addition of the epoxide (7) to butadiene to generate (6) directly, ring-opening of the bicyclic epoxides (6) and (12) to give diastereoisomeric pairs of β-hydroxyphosphine oxides, and stereospecific fragmentation of the latter to the bicyclic trans-cyclo-octenes.