Phase CYCLOPS

To suppress other interference effects, the phase of the transmitter pulse is also shifted by 180° and the signals subtracted from sections A and B, leading to the CYCLOPS phase cycling scheme shown in Table 1.4, in which the two different receiver channels differing in phase by 90° are designated as 1 and 2 and the four different receiver pulses (90°, 90°, 90° and 90f,) are called x, y, — x, and —y, respectively. 

Figure 1.43 The first two steps of the CYCLOPS phase cycling scheme. Any imbalance in receiver channels is removed by switching them so they contribute equally to the regions A and B of the computer memory.

CYCLOPS A four-step phase cycle that corrects dc imbalance in the two channels of a quadrature detector system. 

Quadrature images Any imbalances between the two channels of a quadrature detection system cause ghost peaks, which appear as symmetrically located artifact peaks on opposite sides of the spectrometer frequency. They can be eliminated by an appropriate phase-cycling procedure, e.g., CYCLOPS. 

Quadrature images in the Fi dimension can be suppressed by expanding the 8-step phase cycle to 32 steps or 16 steps, respectively, using CYCLOPS [20] or 2-step CYCLOPS [21]. In the CYCLOPS scheme, the phases of all pulses are simultaneously incremented by 90°, 180° and 270°. In the 2-step CYCLOPS scheme, the incrementation of the pulse phases is limited to the 90° step. 

Four-membered rings can be synthesised by [2 + 2] cycloadditions. However, thermal [2 + 2] cycloadditions occur only with difficulty they are not concerted but involve diradicals. Photochemical [2 + 2] reactions are common and although some of these may occur by a stepwise mechanism many are concerted. An example of a [2 + 2] reaction is the photodimerisation of cyclopent-2-enone. This compound, as the neat liquid, or in a variety of solvents, on irradiation with light of wavelength greater than 300 nm (the n - n excited state is involved) is converted to a mixture of the head-to-head (48) and head-to-tail (49) dimers, both having the cis,anti,cis stereochemistry as shown. It is believed that the reaction proceeds by attack of an n - n triplet excited species on a ground state molecule of the unsaturated ketone (Section 2.17.5, p. 106). In the reaction described (Expt 7.24) the cyclopent-2-enone is irradiated in methanol and the head-to-tail dimer further reacts with the solvent to form the di-acetal which conveniently crystallises from the reaction medium as the irradiation proceeds the other dimer (the minor product under these conditions) remains in solution. The di-acetal is converted to the diketone by treatment with the two-phase dilute hydrochloric acid-dichloromethane system. 

Fig. 16. Pulse sequence used in slow-spinning version of DECODER experiment. Each of the solid rectangles represents a 90° pulse. Standard CYCLOPS and spin-temperature alternation were used for phase cycling, (b) Pulse sequence used in the 3D experiment the phase cycling for the t part was similar to Grans170. (Adapted from Lewis et al.260 with permission.)...

To eliminate these artifacts we make use of our ability to alter the phases of the pulse itself and of the reference signal and to select the portions of computer memory in which the digitized signals are stored. The standard method of eliminating these three types of artifacts is a four-step cycle [often called CYCLOPS (icyclic observe phases)].To see the rationale of the method, consider first an example in which the discrepancy lies only in an amplitude imbalance. Suppose that in the first step we store the output of detector A in computer location I and the output from detector B in location II. From Eq. 3.9, we have, then, in storage... 

A DC offset between the two channels is not eliminated by this cycle but is eliminated by a two-pulse cycle in which the phase of the transmitter is altered by 180° on successive acquisitions and the resulting signals are alternately added and subtracted. Because the desired Fourier-transformed signal changes sign while the DC offset does not, subtraction cancels the offset but causes all real signals to add. To cancel both channel imbalance and DC offsets simultaneously, we must nest our original two-pulse cycle in a two-pulse phase-alternated cycle to produce the four-step CYCLOPS cycle ... 

As we see in later chapters, a number of types of phase cycling are critical to the execution of many 2D experiments. The procedures are similar to that used in CYCLOPS, but the details vary depending on the particular type of signal that must be suppressed. Meanwhile, in addition to any phase cycling unique to the 2D experiment, the complete four-step CYCLOPS cycle is often needed to suppress the quadrature detection artifacts, with the result that long cycles (16 to 64 steps) may be needed, with consequent lengthening of experimental time. 

If CYCLOPS is used to eliminate artifacts in quadrature detection, this eight-step cycle must then be nested within CYCLOPS to give a 32-step cycle overall. In this simple treatment we have not taken into account the effect of pulse imperfections, which generate additional coherence pathways from coherences that were found to vanish in the preceding analyses, so that further phase cycling is often necessary. 

Ellman utilized the Suzuki coupling twice between a support-bound vinyl bromide and an alkyl 9-BBN derivative in a solid-phase synthesis of E- and F-series prostaglandins. The Suzuki reaction was performed in situ, with the hydroboration of a terminal olefin being followed by the palladium-mediated step. This sequence is attractive in library synthesis because of the wide range of suitable commercially available alkenes. The inspiration behind this chemistry was the solution-phase work of Johnson and Braun, where the couplings of 35 with 2-iodo-4-(silyloxy)cyclopent-2-enone 36 went well at room temperature with PdCljCdppO-AsPhj as catalyst (Scheme 41). The modular chemistry demonstrated in this paper was clearly amenable to adaptation to a solid-phase strategy. 

Figure 3.8. Quadrature phase sensitive detection along with the phase cycling and signal routing used in CYCLOPS for eliminating quadrature artefacts.

For H NMR spectra, the number of scans should be a multiple of 4, since this is the length of the CYCLOPS phase cycle used to minimize imperfections associated with quadrature signal detection (Section 5-8). Anywhere from 4 to 128 scans are usually sufficient to obtain a good spectrum with a relatively flat baseline. This number, however, depends heavily on the concentration of the sample. Nevertheless, accumulation times of over 1 hour are relatively rare. 

Table 2.2.2 The CYCLOPS sequence for transmitter and receiver phase cycling...

A tandem RCM-cleavable linker for application to the solid-phase synthesis of oligosaccharides has recently been reported [136]. The system makes use of a tri-ene linker system, resulting in the fact that the RCM regenerates the active Ru catalyst without the need for an alkene co-factor. The application of this hnker was demonstrated in the hberation of a cyclopent-2-enyl mannoside from the solid support. Subsequent isomerization to the vinyl ether glycoside led to the depro-tected mannose after iodine treatment. The basic principle of the approach is out-hned in Scheme 52. 

FIGURE 16 6 Polystyrene/divinylbenzene sulfmate [432] resin was used to prepare the indicated sulfone oxirane on a solid phase. This was subjected to epoxide ring-opening with Grignard and cuprate reagents. Subsequent oxidation of the secondary alcohol was accomplished with simultaneous release from the resin, affording substituted cyclopent-2-enones. 

Table 3.1. The four-step CYCLOPS phase cycle illustrated in Fig. 3.26...

Figure 3.26. Phase cycling. The CYCLOPS scheme cancels unwanted artefacts whilst retaining the desired NMR signals. This four-step phase cycle is explained in the text.

The basic components of the INADEQUATE phase cycle comprise doublequantum filtration and fi quadrature detection. The filtration may be achieved as for the DQF-COSY experiment described previously, that is, all pulses involved in the DQ excitation (those prior to ti in this case) are stepped x, y, —X, —y with receiver inversion on each step (an equivalent scheme found in spectrometer pulse sequences is to step the ftnal 90° pulse x, y, —x, —y as the receiver steps in the opposite sense x, —y, —x, y, other possibilities also exist). This simple scheme may not be sufficient to fully suppress singlet contributions, which appear along fi = 0 as axial peaks and are distinct from genuine C-C correlations. Extension with the EXORCYCLE sequence (Section 7.2.2) on the 180° pulse together with CYCLOPS (Section 3.2.5) may improve this. Cleaner suppression could also be achieved by the use of pulsed field gradients, which for sensitivity reasons requires a gradient probe optimised for C observation. 

CYCLOPS Cyclically-ordered phase-sequence (for suppressing quadrature artefacts) 3.2.5... 

The CYCLOPS phase cycling scheme is commonly used in even the simplest pulse-acquire experiments. The sequence is designed to cancel some imperfections associated with errors in the two phase detectors mentioned above a description of how this is achieved is beyond the scope of this discussion. However, the cycle itself illustrates very well the points made in the previous section. 

If time permits we sometimes add CYCLOPS-style cycling to all of the pulses in the sequence so as to suppress some artefacts associated with imperfections in the receiver. Adding such cycling does, of course, extend the phase cycle by a factor of four. 

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