5.12 Six-membered Rings with One Phosphorus Atom DAVID G. HEWITT Monash University, Victoria, Australia 5.12.1 INTRODUCTION 640 5.12.2 THEORETICAL METHODS 640 5.12.3 EXPERIMENTAL STRUCTURAl 13 3lL METHODS 642 5.12.3.1 NMR Spectroscopy ( H, C, P) 642 5.12.3.2 X-Ray Spectroscopy 643 5.12.3.3 Mass Spectrometry 643 5.12.3.4 Miscellaneous Spectroscopic Methods 643 5.12.4 THERMODYNAMIC ASPECTS 644 5.12.5 REACTIVITY OF FULLY CONJUGATED RINGS 646 5.12.5.1 Reactions at the Heteroatom 646 5.12.5.2 Reactions at Carbon 647 5.12.5.3 Reaction of V-Substituents 648 5.12.5.3.1 Ring reactions 648 5.12.6 REACTIONS OF NON-CONJUGATED RINGS 650 5.12.6.1 Dihydro Derivatives—Ease of Aromatization and Reactions 650 5.12.6.2 Tetrahydro Derivatives 651 5.12.6.3 Hexahydro Derivatives—Phosphorinanes 652 5.12.7 REACTIVITY OF SUBSTITUENTS ON RING CARBON ATOMS 652 5.12.8 REACTIVITY OF SUBSTITUENTS ON RING HETEROATOMS 654 5.12.9 RING SYNTHESES CLASSIFIED BY NUMBER OF RING ATOMS IN EACH COMPONENT 654 5.12.9.1 PC Cyclizations 654 5.12.9.1.15 Formation of the P—C bond 654 5.12.9.1.2 Formation of the C(2)—C(3) bond 655 5.12.9.1.3 Formation ofthe C(3)—C(4) bond 655 5.12.9.2 [2 + 4J Cycloadditions Involving P—C Multiple Bonds 656 5.12.9.2.1 PC + C' Cycloadditions 656 5.12.9.2.2 PC + C4 Cycloadditions 659 5.12.9.2.3 P+C3 Cyclizations2 659 5.12.9.2.4 Addition5 ofP(III) to 1,5-diketones 660 5.12.9.2.5 Addition ofP(IH) to alkene-unsaturated C=O 660 5.12.9.2.6 Addition ofP(III) to dienes 661 5.12.9.2.7 Addition of P(III) to 1,5-dihalo compounds 662 5.12.9.3 PC +C Reactions 663 2 3 5.12.10 RING SYNTHESIS BY TRANSFORMATION OF ANOTHER RING 663 5.12.10.1 Synthesis via Ring Expansion 663 5.12.10.1.1 Synthesis via ring expansion of dihydrophospholes using carbenes 663 5.12.10.1.2 Synthesis via ring expansion 664 5.12.10.2 Synthesis via Ring Contraction 666 639 640 Six-membered Rings with One Phosphorus Atom 5.12.11 SYNTHESIS OF ANALOGUES OF NATURAL PRODUCTS 666 5.12.12 IMPORTANT COMPOUNDS AND APPLICATIONS 667 5.12.1 INTRODUCTION Six-membered rings containing one phosphorus atom were concisely covered as a small part of Volume 1 in the first edition of Comprehensive Heterocyclic Chemistry (CHEC-I) <84CHEC-I( 1)493). There are about 600 references which post-date 1980 and they show a steady development of both theoretical understanding of the aromatic phosphorins and of synthetic methods. Probably the most notable of these have been in the applications of multiply bonded phosphorus species in cyclo- addition reactions, the carbene-induced ring-opening reactions of phospholes, and the exploitation of a general route for the synthesis of phosphorus analogues of sugars. A deliberate decision was made to exclude from this section papers of predominantly inorganic interest, bridged-ring systems and systems containing heterocyclic ring(s) fused to the phosphorus-containing ring. General reviews relevant to this topic include "A decade of research in phosphinine chemistry" <92HACl>, "Cyclic phosphines" <90Mi 512-01), and "Phosphabenzen5 e and arsabenzene. Higher element homologs of pyridine" <82MI 512-01 >, "The 2 -phosphorins" <82ACR58>, "Phosphines and phosphonium salts" <82MI 512-02), and "Synthesis and heterocyclization of oxoalkoxyl derivatives of tricoordinate phosphorus acids" <91ZOB10). An early, but very comprehensive, summary was provided in 1978, by Atkinson <78MI 512-0). Reviews on specific sections are mentioned in appro- priate sub-sections. There is some disagreement in the literature as to the best nomenclature for these compounds. IUPAC <83PAC409) proposed that the six-membered saturated rings be named as derivatives of phosphinane and the unsaturated compounds as phosphinines. Chemical Abstracts prefers the older phosphorinane and phosphorin and has completely ignored the IUPAC recommendation. This also follows the lead set by Atkinson <78MI 512-0) and Dimroth <84CHEC-I( 1)493). No authors seem to have used phosphinane, although phosphinine is quite common. For consistency, the Chemical Abstracts system is used throughout this chapter. IUPAC has no specific recommendations for the di- and tricyclic compounds, and the general line taken by Chemical Abstracts and the Ring Index is that the names be based on the corresponding non-systematic names used for the nitrogen analogues. In some special cases, the valence3 of4 the phosphoru5 s atom, particularl3 y in unsaturated molecules, is indicated by the designations 2 , 2 , and X (see (1) and (2)). A -Phosphorin (1) is also widely referred to as phosphabenzene, a designation which reflects both its structure and the nature of many of its reactions. In an attempt to clarify this confusing situation, some of the names commonly used are summarized in Figure 1. The numbering is taken from Chemical Abstracts. 5.12.2 THEORETICAL METHODS Most theoretical interest ha3 s been in questions of aromaticity in fully unsaturated molecules. It is5 generally concluded that A -phosphorin (1) behaves as a fairly classical aromatic system, whereas i -phosphorins (2) may be considered as either aromatic or as phosphonium ylides. Several papers concern the idea of aromaticity as a quantitative concept and the application of an aromaticity index.5 On a scale where benzene ranks 100, P-phosphorin (74) ranks somewhat below pyridine (86) but /l -phosphorins with appropriate substituents on phosphorus may be comparable to pyridine according to this scale (R = OMe 81, R = NMe 69, R = Me 66) <86T89,90JPR885,90T5697)1 . AMI was used 1to calculate the aromatic energie1 s of benzene (28.3 kcal mol" ), phosphabenzene (26.0 kcal mol" ), pyridine (25.6 kcal mol" ), and other heterocycles <89H(28)ll35> and CNDO/S methods showed good correlation of calculated transition energies with experimentally observed values. The calculated value for the dipole moment of phosphabenzene was 2.38 D compared with an exper- imental value of 1.46 + 0.4 D. The CNDO method has the potential for wide application to the calculation of electronic states of many aromatic and heterocyclic compounds containing second- row elements <85CPB3077>. Absolute hardness, related to the gap between HOMO and LUMO energies, also provides a theoretical parameter to recognise aromaticity. Using this measure phos- phabenzene (1.66 eV) is a little less aromatic than benzene (2.27 eV) <93OM5005>. The ab initio stabilization energy of phosphabenzene has been calculated <9OMI 512-02). In a related study, calculations were made using ab initio molecular orbital (MO) theory to compare the properties of Six-membered Rings with One Phosphorus Atom 641 P p i 1 l H a (1) a Phosphorinaneb Phosphorin b Phosphinoline* Isophosphinoline Phosphinane Phosphinine Phosphabenzen3 e A, -Phosphorin P 1 2//-Phosphinolizine B enzo [g] phosphinoline Benz[g]isophosphinoline 2 1 P 2 3 P 8 5 Acridophosphine Benzo[/z]phosphinoline B enz [h] isophosphinoline Benz[/]isophosphinoline Phosphanthridine Benzo[/]phosphinoli ne l 10 d P e 5 (2) Phosphorino[2,1,6-de]phosphinolizine l//,5//-Phosphorino- X, -Phosphorin [3,2, l-//]-phosphinoline a Figure 1 Nomenclaturb e of six-membered heterocycles containing one phosphorus atom ( Chemical Abstracts; IUPAC <83PAC409>; where only one name is given, source is Chemical Abstracts). heterabenzenes, with the heteroatoms taken from the block in the periodic table bounded by Groups IVA-VIA and periods 2-5. A small decrease in delocalization energy is found between benzene and phosphabenzene <88JA4204>. A Hartree-Foch SCF study concluded that electron population at P—C correlated strongly with bond length and bond order, integrated electron populations correlated with coordination number, and the integrated charge indicated a strongly polarized C—P bond in both saturated and unsatu- rated compounds <89MI 512-01). However, dipole moment calculations for some dicoordinated phosphorus compounds showed the C=P bond to be practically non-polar in phosphaalkenes but slightly polar in phosphabenzenes <88ZOB1464>. Calculated polarizability for phosphabenzene agrees with experimental data <94MP557>. Comparison of 7r-ionization energies of 28 compounds containing X=C double bonds (X = CH, N, P) revealed a larger similarity between carbon and phosphorus than between nitrogen and phosphorus. This suggested that although the strength of the P=C bond is significantly less than that of the C=C or C=N bond, in conjugative interactions P=C is more comparable to C=C than to C=N, which is consistent with similarity observed in reactions 642 Six-membered Rings with One Phosphorus Atom <93JPC40ll>. Theoretical studies of the gas-phase proton affinities of molecules containing phos- phorus—carbon multiple bonds, including phosphabenzene, show a slight favour for protonatio1n at phosphorus over carbon. The isomerization energy between the two sites is about 50 kJ mol" . In contrast, phosphaethyne shows a strong preference for protonation on carbon. Relationships with the basicity of the corresponding nitrogen compounds have been discussed <(84JPC1981, 93UQ343). An ab initio study of a reaction important in the synthesis of phosphorinanes, the Diels-Alder reaction of aza1 - and phospha-l,3-butadienes with ethylene, indicate1 d small activation energies (20- 28 kcal mol" ) and high exothermicity (about —43 kcal mol" ). The 1-phospha compounds are a little more reactive than the 2-phospha compounds and both are substantially more reactive than the aza-analogues—so reactive, in fact, that the lightly substituted molecules may not be isolated, instead undergoing spontaneous [4 + 2] cycloaddition (84CB3151,91HAC651). The method used was not able to determine the precise synchronicity of the reactions (92JOC6736).