Phosphazene superbase

The phosphazene bases BTPP and Bu-P2 mediate the rearrangement of unactivated A -alkyl-(9-benzoyl hydroxamic acid derivatives to give 2-benzoyl amides. The rate of reaction was found to be dependent upon the steric nature of the A -alkyl substituent [39a]. Treatment of malonyl derived (9-acyUiydroxamic acid derivatives with the phosphazene superbase Bu-P2 gives 2,3-dihydro-4-isoxazole carboxylic ester derivatives. The rate and yield of the reaction depend upon the (9-acyl substituent [36b] (Scheme 5.21). 

Compounds containing a l,5-hexadien-3-ol system undergo anionic oxy-Cope rearrangement when treated with the phosphazene superbase Bu-P4. The sigmatropic rearrangement occurs in hexane as well as in THF. The weaker phophazene base Et-P2 failed to induce rearrangement. This is the first example of the use of a metal-free base to induce anionic oxy-Cope rearrangement [49] (Scheme 5.30). 

Lash, T.D., Thompson, M.L., Werner, T.M. and Spence, J.D. (2000) Synthesis of novel pyrrolic compounds from nifroarenes and isocyanoacetates using a phosphazene superbase. Synlett, 213-216 Murashima, T., Tamai, R., Nishi, K. et al. (2000) S3mthesis and X-ray structure of stable 2JS-isoindoles. Journal of the Chemical Society - Perkin Transactions, 1, 995-998. 

In this chapter, applications of amidine, guanidine and phosphazene superbases to the synthesis of natural products have been discussed. Many structurally complex natural products have been synthesized efficiently and elegantly by making use of the reactions described. Currently, much attention is focussed on the development of chiral superbases and their application to asymmetric reactions. Such catalytic asymmetric reactions are expected to offer exciting and efficient new approaches to the synthesis of natural products and biologically active compounds. 

Phosphazene superbases (stmctures 10 and 11) have recently been explored as extremely effective initiators of the ROP of cyclosiloxanes. " Neutral phosphazene bases (10, 11) require a proton donor, such as methanol, to form the tme initiator, phosphazenium alkoxide (eqns [17] and [18]). Bulky phosphazenium cations are able to very effectively stabilize a positive charge by the resonance effect. The existence of the bare silanolate anion in such systems is very probable. They are also well soluble in the polymerization system. 

P4-/-Bu = superbase phosphazene [3-(/ v/-butylimino)-1,l,l,5,5.5-hcxakis(dimethylamino)-3-[[tris(dinicthy]amiiio)phosphorany]ideneJamino -l 3/.5, 525-1,4-triphosphazadiene]. 

This result has been further substantiated by the work of Koppel et al. <2001PCA9575>. They conducted a theoretical study of the basicity of phosphorus imines and ylides. Verkade bases 6-8 were included. They showed basicities comparable to commercially used organic superbases (/-BUP4 phosphazene imine), with compound 8 in particular giving calculated basicities similar to Li3P and Li20. 

T4.5 Start from Section 4.14 Superacids and superbases which covers classical examples of superbases, nitrides, and hydrides of s-block elements. However, there are several groups of superbases that you can look at. For example, amides (diisopropylamide related) are commonly used superbases. More modem are phosphazene bases which are neutral rather bulky compounds containing phosphorus and nitrogen. An interesting topic is a proton sponge (or Alder s base) and its derivatives as well as several theoretical and practical approaches used in rational design of superbases. 

Superbases for Organic Synthesis Guanidines, Amidines, Phosphazenes and Related Organocatalysts Edited by Tsutomu Ishikawa 2009 John Wiley Sons, Ltd. ISBN 978-0-470-51800-7... 

Allen, C.W. (1994) Linear, cyclic, and pol3mieric phosphazenes. Coordination Chemistry Reviews, 130, 137-173 AUen, C.W. (1996) Phosphazenes. Organophosphorus Chemistry, 27, 308-351 Kondo, Y., Ueno, M. and Tanaka, Y. (2005) Organic synthesis using organic superbase. Journal of Synthetic Organic Chemistry, 63, 453 63. 

Calculations have revealed that the proazaphosphatrane bases are approximately equal in thermodynamic basicity to the Schwesinger P2 phosphazene bases (Table 2.14). The RHF/ 6-3IG calculations of proton affinities indicate that phosphazene (Z = NH) and phosphorus ylide (phosphorane, Z = CH2) counterparts (146 and 145) are stronger than the parent Verkade superbase 139. Higher basicity is associated with the higher degree of delocalization of the positive charge in the protonated iminophosphoranes and phosphorus ylides as a result of the more electropositive character of phosphorus atom [67]. On the other hand, phosphoms oxides 147 and 150 are weaker than 139, but still above the superbasicity borderline. The strained polycycles 138, 149 and 148, as representatives of superbases... 

In summary, guanidinophosphazenes belong to the most basic, experimentally determined class of superbases, followed by phosphazenes, proazaphosphatranes and guanidines. Amidines and classical proton sponges generally show less pronounced basicity. 

Kaljurand, I., Koppel, I.A., Kiitt, A. et al. (2007) Experimental gas phase basicity scale of superbasic phosphazenes. Journal of Physical Chemistry A, 111, 1245-1250. 

Kovacevic, B., Baric, D. and Maksic, Z.B. (2004) Basicity of exceedingly strong non-ionic bases in acetonitrile - Verkade s superbase and some related phosphazenes. New Journal of Chemistry, 28, 284-288. 

A density functional theory (B3LYP/6-311 - -G ), ab initio (HF/3-21G ) and semi-empirical (PM3) study of intrinsic basicities, protonation energies or protonation enthalpies of phosphazene bases has been reported. The study shows that the organic superbases can reach the basicity level of the strongest inorganic superbases, such as alkali metal... 

The oxy-Cope rearrangement reaction provides useful synthetic intermediates for natural products. Since the oxy-Cope rearrangement is known to be greatly accelerated when the alkoxide is used instead of the corresponding alcohol, metal-free superbases were applied to the reaction by Mamdani and Hartley [12], Reaction of the alcohol 51 with phosphazene 9 at room temperature gave the rearranged product 52 in 53% yield (Scheme 7.9). 

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